bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19778: Novel Strategy for Improved Substrate Mapping of the Atria: Omnipolar Catheter and Signal Processing Technology Assesses Electrogram Signals Along Physiologic and Anatomic Directions
Authors: Deno D Curtis , Balachandran Ram , Morgan Dennis , Massé Stéphane , Nanthakumar Kumaraswamy
Published: July 2021

Introduction:
Substrate mapping is evolving as a potential strategy for atrial fibrillation ablation. Defining scar borders and functional boundaries is typically under taken with bipolar electrodes. Catheter orientation affects electrogram (EGM) signal amplitude due to an orientation dependence of bipoles. We developed orientation independent Omnipolar Technology (OT) and compared OT EGM amplitude with traditional bipolar (Bi) methods.

Methods:
Four anesthetized swine were studied in 6 sessions with a 3D mapping system and a multielectrode OT ablation catheter placed in RA and LA locations in 4 rhythms. With the OT catheter in a stable location, 30 successive atrial beats were acquired. OT electrodes provided bipole (Bi) as well as OT signals along both activation (OTa) and surface normal (OTn) directions. Peak to peak amplitudes (Vpp) of OT and Bi signals were compared for magnitude and consistency.

Results:
As shown in the table, OT signal amplitudes over all atrial locations and rhythms were greater than traditional bipole amplitudes. The coefficients of variation for signal amplitude over successive cardiac beats were substantially less for OTa and OTn (*p < 0.01 with respect to Bi) than for Bi, reflecting electrode pair orientation effects.

Conclusions:
Distinct electrogram signals were resolved by OT along physiologic (activation) and anatomic (surface normal) directions. Catheter orientation independent OT signal amplitudes were more self-consistent and reliable than those from orientation dependent bipolar electrode pairs. Omnipolar technology approaches may permit more accurate and specific definition of substrate and thus catheter ablation of arrhythmias.
Abstract 19823: Japanese Multicenter Study on the Prognostic Efficacy of Out-patient Cardiac Rehabilitation in Patients With Coronary Artery Disease: J-REHAB
Authors: Goto Yoichi , Nohara Ryuji , Daida Hiroyuki , Masuda Takashi , Kohzuki Masahiro , Makita Shigeru , Ueshima Kenji , Origuchi Hideki , Adachi Hitoshi , Nagayama Masatoshi , Omiya Kazuto , Nishizaki Mari , Kimura Yutaka , Yasu Takanori , Tsurukawa Toshihiro , Momomura Shin-ichi
Published: July 2021

Introduction:
Although the prognostic efficacy of out-patient cardiac rehabilitation (OPCR) in patients with coronary artery disease (CAD) has been established in Western countries, it has not been studied in Japan, where both incidence and mortality of CAD are known to be much lower than in Western counties.

Methods:
To determine the prognostic efficacy of OPCR in Japan, a prospective, controlled, multicenter study of OPCR (J-REHAB) was conducted in 15 hospitals in Japan. A total of 1047 patients hospitalized with cardiac events were prospectively assigned to either OPCR group (n=848) or Non-OPCR group (n=199) according to patient’s preference at the time of hospital discharge. Patients in OPCR group were scheduled to participate in a comprehensive OPCR program for 3 months and Non-OPCR group received usual care. Event-free survivals for cardiac and all-cause death/rehospitalization were assessed according to the initial group assignment and the “prespecified” actual OPCR performance (attendance >=4 times/month and total exercise time >=150 min/week).

Results:
Patients were followed-up for 416days on average and the follow-up rate was 99.4%. At baseline, patients were 64±11years of age, 85% was male, 58% acute myocardial infarction, with preserved EF (53±13%). By Kaplan-Meier analysis, OPCR group had significantly better event-free survival for cardiac death/rehospitalization (p<0.05) and all-cause death/rehospitalization (p<0.001) than Non-OPCR group. However, after Cox proportional hazard analysis including patient characteristics (underlying heart disease, NYHA class, EF, residual coronary stenosis, heart rate, peak oxygen uptake, and ACE inhibitor/ARB), these differences were no more significant. In contrast, Cox analysis based on prespecified actual OPCR performance (good [n=352], partial [n=321], and poor [n=374]) revealed that good OPCR performance (i.e., active participation) was a potent independent determinant of both cardiac and all-cause event-free survival (both p<0.01).

Conclusions:
The first Japanese prospective multicenter J-REHAB study has demonstrated that active participation in OPCR is associated with better event-free survival in CAD patients, independent of baseline clinical characteristics.
Abstract 19826: Utility of Stroke Volume Index for Stratification of Patients With Low Gradient Severe Aortic Stenosis and Normal Left Ventricular Ejection Fraction
Authors: Shen Hong , Stacey Brandon , Applegate Bob , Zhao David , Vasu Sujethra , Upadhya Bharathi , Gandhi Sanjay , Liu Rong , Wei Meng , Pu Min
Published: July 2021

Background:
Decision of intervention for low gradient severe aortic stenosis (AS) with normal left ventricular ejection fraction (LVEF) is clinically challenging. The study was to determine the impact of stroke volume index (SVi) on prognosis in patients (pts) with AS.

Methods:
We examined 410 pts with moderate or severe AS and normal EF (≥50%). Pts were divided into four groups based on aortic valve area (AVA), mean pressure gradient (MPG) and SVi: Group I: low flow low gradient severe AS (AVA≤1.0cm
2
, MPG<40mmHg and SVi<35mL/m
2
, n=75); Group II: normal flow low gradient severe AS (AVA≤1.0cm
2
, MPG<40mmHg and SVi≥35mL/m
2
, n=97); Group III: severe AS with matched gradient-AVA (AVA≤1.0cm
2
and MPG≥40mmHg, n=88); Group IV: moderate AS (AVA>1.0cm
2
and MPG>20mmHg, <40 mmHg, n=150). Aortic valve gradients, AVA and SVi were assessed by echocardiography. Clinical charts were reviewed. Mean follow-up duration was 3.2±1.6 years.

Results:
Group I had higher prevalence of atrial fibrillation, more pronounced LV hypertrophy, lower SVi, smaller AVA, higher valvuloarterial impedance (Zva) (Table) and lower 3-year cumulative survival compared to Group II and Group IV (61% vs. 75% and 80%, p=0.004). Group II had a 3-year cumulative survival similar to moderate AS (75% vs. 80%, p>0.05). In pts with medical management, Group I and Group III had lower 3-year cumulative survival in comparison with Group II and Group IV (48% and 56% vs. 73% and 76%, p=0.001). Multivariate analysis showed SVi was a strong predictor of mortality in low gradient severe AS (HR 0.95, CI: 0.91-0.99, P=0.02). However, in gradient-AVA matched severe AS and moderate AS, SVi was not associated with mortality (p>0.05).

Conclusions:
Without AS intervention, low flow low gradient severe AS with normal EF carries poor prognosis similar to high gradient AS, but normal flow low gradient AS does not, suggesting that SVi may be used to identify the pts benefiting most from AS intervention in pts with low gradient AS.
Abstract 19828: Real-world Assessment of Patients Switching From Warfarin to Non-vitamin K Oral Anticoagulants Using MarketScan EarlyView Data
Authors: Masseria Cristina , Mardekian Jack , Phatak Hemant , Kamble Shital , Ravee Yaniv , Abdulsattar Younous , Petkun William
Published: July 2021

Background:
Non-valvular atrial fibrillation (NVAF) was commonly treated with warfarin. With the introduction of Non-Vitamin K Oral Anticoagulants (NOACs) in the United States, some patients are switching from standard of care to NOACs

Purpose:
To investigate demographic and clinical characteristics associated with switching among NVAF patients treated with warfarin to a NOAC (apixaban, dabigatran and rivaroxaban).

Methods:
A retrospective cohort study was conducted using Truven MarketScan EarlyView data. The patient recruitment period was from 01/12/2012 to 01/31/2015. Study enrolled adult NVAF patients ≥18 years with 2 or more warfarin prescriptions at least 90 days apart, with 6 months continuous enrollment prior to their last warfarin prescription. Warfarin switch to NOAC will be defined for patients who had a pharmacy claim of NOACs within 60 days from the last day of supply of the last filled prescription of warfarin. Stepwise logistic regression was used to identify patient characteristics associated with switching status (yes or no).

Results:
A total of 141,198 eligible patients were identified, apixaban n=2177, dabigatran n=771, rivaroxaban n=4317 and non-switchers n=133,933.Cardioversion was identified as the variable most significantly associated with switching followed in order by health plan type, hypertension, age, Charlson Comorbidity Index (CCI), stroke, days on warfarin, and bleeding history. On average people who undergo cardioversion, with hypertension at baseline, with prior stroke, with a history of bleeding, and with a longer exposure to warfarin treatment were more likely to switch to a NOAC than to continue warfarin treatment. NVAF elderly patients and those with multiple comorbidities were more likely to continue warfarin treatment.

Conclusion:
In the real world setting, by using a stepwise logistic regression, cardioversion, health plan type, hypertension, age, CCI, stroke, days on warfarin and bleeding history were the main demographic and clinical characteristics associated with switching from warfarin to a NOAC.
Abstract 19837: DJ-1/Park7 Protects the Heart Against Ischemia-reperfusion Injury Through the Modulation of SUMOylation
(Best of Basic Science Abstract)
Authors: Shimizu Yuuki , Barr Larry , Fields Travis , Calvert John W
Published: July 2021

Background:
DJ-1/Park7 is a ubiquitously expressed protein typically associated with the development of early onset Parkinson’s disease. Recent data suggests that it also plays a role in the cellular response to stress. Although much is known about DJ-1 in the brain, very little has been investigated in the heart. Here, we aimed to examine the underlying molecular mechanisms mediating the actions of DJ-1 in the heart following the onset of myocardial ischemia-reperfusion (I/R) injury.

Methods and Results:
Wild-type (WT) control and DJ-1 deficient (DJ-1 KO) mice were subjected to in vivo myocardial I/R injury. DJ-1 KO mice (n=9) displayed increased areas of infarction (%INF/LV or AAR: 30.2 vs 22.0%, 53.6 vs 39.0%, Troponin-I: 47.4 vs 19.9ng/ml, p<0.05 respectively) and worsened left ventricular function (LVEF: 43.7 vs 58.1%, p<0.001) when compared to WT mice (n=9), confirming a protective role for DJ-1 in the heart. In an effort to evaluate the potential mechanism(s) responsible for the increased injury in DJ-1 KO mice, we focused on SUMOylation, a post-translational modification process which regulates various aspects of protein function, including transcription, subcellular localization, DNA repair, and cell cycle. DJ-1 KO hearts after I/R injury were found to display enhanced accumulation of SUMO-1 modified proteins, (this modification is generally associated with cell injury), and reduced SUMO-2/3 modified proteins (this modification is generally associated with cytoprotection). Further analysis, revealed that the protein expression of the de-SUMOylation enzyme SENP-1 (removes SUMO-1 modifications) was reduced, whereas the expression of SENP-5 (removes SUMO-2/3 modifications) was enhanced in DJ-1 KO hearts after I/R injury. Changes in mRNA levels did not account for the altered protein expression of SENP-1 and SENP-5. So, we evaluated the direct interaction of DJ-1 with both proteins in hearts of WT mice following I/R using co-immunoprecipitation. We found that SENP1 binding with DJ-1 was down-regulated, whereas SENP5 binding with DJ-1 was up-regulated.

Conclusion:
Our data demonstrated that the activation of DJ-1 in response to myocardial I/R injury protects the heart by the modulation of SUMOylation via direct binding of SENP1 and SENP5.
Abstract 19843: Myocardial Microcirculation Induces Anisotropic Diffusion-like Magnetic Resonance Contrast
Authors: Abdullah Osama , Gomez Arnold David , Merchant Samer , Heidinger Michael , Poelzing Steven , Hsu Edward
Published: July 2021

Introduction:
The magnetic resonance (MR) signal in the presence of a magnetic field gradient is highly sensitive to the aggregate translational molecular motion of water. In highly vascularized tissues, diffusion-like contrast induced by microcirculation has been used to characterize blood flow in heart. The effect in tissues with random capillary orientations has been modeled as intravoxel incoherent motion (IVIM), but is not completely understood in organized tissues.

Hypothesis:
We hypothesize that blood flow in organized tissues will manifest as speed- and orientation- dependent “pseudo” diffusion coefficient D*.

Methods:
For Gaussian-distributed flow with mean speed vm in parallel capillaries as a function of the relative encoding angle θ, it can be shown that D* is proportional to the square power of both vm and cos(θ), which is then incorporated into a generalized formulation of anisotropic tissue diffusion and flow with a tensor entity D* to characterize the flow pseudo diffusivity in 3D space using the familiar diffusion tensor imaging (DTI) notation. Validation experiments were conducted on isolated, perfused, guinea pig hearts (n=7) in a Langendorff setup and imaged with Bruker (7T) MRI scanner under normal and low flow conditions. Statistical analyses were conducted via 1-way ANOVA with Bonferroni post-hoc multiple-comparison correction (P<0.05 considered statistically significant).

Results:
Figure 1A-C show representative diffusion-weighted MR images encoded at perpendicular directions, and Fig 1D shows the flow-speed and angular dependence (or anisotropy) of the fitted D* component at high flow and low flow. D* significantly decreased by 63% only in the parallel direction to myocytes (or capillaries) (P<0.05).

Conclusions:
These findings suggest that the DTI formalism of anisotropic spin motion can be incorporated into the classical IVIM theory to describe the MR signal arising from diffusion and microcirculation in organized tissues.
Abstract 19890: Pre-operative Cerebral Hemodynamics From Birth Until Surgery in Neonates With Critical Congenital Heart Disease
Authors: Lynch Jennifer M , Newland John J , Winters Madeline , Busch David R , McCarthy Ann L , Xiao Rui , Nicolson Susan C , Montenegro Lisa M , Fuller Stephanie , Gaynor J. W , Spray Thomas L , Yodh Arjun G , LIcht Daniel J , Naim Maryam Y
Published: July 2021

Introduction:
Neonates with critical congenital heart disease (CHD) exhibit a high prevalence of white matter injury (WMI). Recent work in neonates with hypoplastic left heart syndrome has shown that a longer wait from birth to surgery was associated with lower cerebral tissue oxygen saturations (StO2) on the morning of surgery and an increased risk for postoperative white matter injury (WMI). Understanding the daily preoperative changes in cerebral physiology during this vulnerable period may lead to new therapeutic algorithms aimed at prevention of WMI.

Methods:
Term neonates with critical CHD were recruited for this study. Frequency domain diffuse optical spectroscopy was employed to noninvasively quantify StO2. Daily StO2 measurements were made from day of recruitment until the day of surgery.

Results:
We studied 37 neonates with critical CHD. Operations were performed at 1-8 days of life. Non-elective reasons for timing of surgery resulted only in earlier surgery in this cohort. The subjects were placed in 2 groups depending on if they had a normal arch (N=20) or obstructed arch (N=17). In a linear mixed-effects model, StO2 decreased as a function of time from birth but was not specific to diagnostic group.

Conclusions:
Observed longitudinal daily decline in StO2 from birth until surgery supports our earlier findings and extends them to other groups of CHD. These results suggest that reported increases in risk for WMI with time-to-surgery could be due to mismatched oxygen delivery to metabolic demand. Therapeutic interventions such as increasing cerebral blood flow or decreasing cerebral oxygen demand may be considered when earlier surgery is not possible.
Abstract 19936: Venous Thromboembolism Recurrence and Bleeding Risk Among Cancer Patients Using a Large Commercial Database
Authors: Masseria Cristina , Kariburyo Furaha , Mardekian Jack , Lee Theodore C , Ravee Yaniv , Phatak Hemant , Baser Onur , Hamilton Melissa , Xie Lin
Published: July 2021

Objectives:
To describe the role of anticoagulant use, active cancer and venous thromboembolism (VTE) type on bleeding risk and VTE recurrence among cancer patients diagnosed with VTE.

Methods:
A retrospective observational analysis of the Humedica database between 01JAN2008 and 31MARCH2014 was conducted including adult patients (aged >18 years) with ≥2 VTE diagnosis claims (ICD-9-CM codes) in an outpatient setting or with one VTE diagnosis in an inpatient setting who had continuous health plan enrollment 6 months pre-index date. Active cancer patients were differentiated from cancer patients based on diagnosis codes during the baseline period. The incidence rate (in person-years) was calculated for major bleeding and VTE recurrence. Time-to-major bleeding and time-to-VTE recurrence were estimated using Kaplan-Meier curves; a Cox regression was applied to adjust for baseline demographic and clinical characteristics.

Results:
A total of 72,224 cancer patients were identified, which included 8,222 active cancer patients. More than 70% of cancer patients were prescribed anticoagulants. The incidence rate of VTE recurrence (24.7 vs. 14.3 per 100 person-years) and major bleeding events (31.2 vs. 15.9 per 100 person-years) was higher among active cancer patients than all VTE cancer patients. The use of combination parenteral and oral anticoagulant treatment (hazard ratio [HR]=1.30, p<0.0001), active cancer (HR=1.10, p=0.0007) and having both pulmonary embolism (PE) and deep vein thrombosis (DVT) as prior diagnoses (HR=1.17, P<0.0001) were significantly associated with an increased risk of major bleeding. Clinical predictors of VTE recurrence included active cancer (HR=1.35, p<0.0001) and having both PE and DVT as prior diagnoses (HR=1.32, p<0.0001). Patients treated with anticoagulants (HR=0.71, p<0.0001) were at a lower risk of VTE recurrence.

Discussion:
Active cancer and having both PE and DVT as prior diagnoses were associated with increased VTE recurrence and bleeding risk. The bleeding risk was also highest among patients undergoing parenteral and oral anticoagulant therapy. However, anticoagulant treatment was shown to be associated with a lower risk of VTE recurrence.
Abstract 20041: Single Ventricle Outcome Following Neonatal Palliation of Severe Ebstein’s Anomaly With Modified Starnes Procedure
Authors: Kumar S. Ram , Noh Nathan , Castillo Novell , Fagan Brian , Kung Grace , Wells Winfield J , Starnes Vaughn A
Published: July 2021

Background:
We have previously shown that neonates in profound cardiogenic shock due to severe Ebstein’s anomaly can be successfully salvaged with fenestrated right ventricular (RV) exclusion and systemic to pulmonary shunt (modified Starnes procedure). The long-term outcome of single ventricle management in these patients is not known.

Methods:
We retrospectively reviewed the records of 26 patients who underwent neonatal Starnes procedure between 1989 and 2011. Patient demographics, clinical variables and outcome data were collected. Data is presented as mean ± standard errors or median (interquartile ranges).

Results:
26 patients (12, 46% boys) underwent Starnes procedure at 7 (5-9) days of life. All were intubated and on prostacyclin infusion, 24 (92%) were inotrope-dependent and 23 (88%) had no antegrade flow from the RV. Two patients had had prior intervention (one tricuspid annuloplasty and one shunt alone). Three patients underwent non-fenestrated RV exclusion, two (67%) of whom died. Of the remaining 23, 3 (13%) died during the same hospitalization. The 21 neonatal survivors have been followed for 7 (6-8) years. One patient died after Glenn. The remaining 20 have successfully undergone Fontan completion with an indexed pulmonary resistance of 1.8 (1.2-2.3) W/m2 and mean pulmonary pressure of 12 (9-18) mm Hg. At last follow-up, all patients have normal left ventricular function, and all but one patient are in NYHA Class I symptoms. Two patients have required pacemaker implantation, while the rest are in sinus rhythm. Survival at 1, 5 and 10 years are 81±4%, 77±3% and 77±3%, respectively.

Conclusion:
Long-term single ventricle outcomes amongst neonatal survivors of modified Starnes procedure are excellent. There is reliable remodeling of the excluded RV and excellent function of the left ventricle.
Abstract 20065: Periodontitis and Bone Metabolism in Patients With Advanced Heart Failure and After Heart Transplantation
Authors: Schulze-Späte Ulrike , Chang Jaime , Mizani Iman , Rodriguez Salaverry Kristina , Wu Christina , Jones Meaghan , Kennel Peter , Brunjes Danielle , Choo Tse-Hwei , Kato Tomoko , Mancini Donna , Schulze P. Christian
Published: July 2021

Background:
Heart failure (HF) is a multi-organ, pro-inflammatory syndrome that impairs bone metabolism. Proinflammatory cytokines and bone catabolism enhance periodontal disease, a local inflammatory, bacteria-induced disease that causes bone loss and periodontal soft tissue destruction.

Hypothesis:
Patients with advanced HF before and after heart transplantation (HTx) have more severe periodontal disease as compared to age and smoking-matched controls. Further, local inflammatory markers in the saliva and gingival crevicular fluid (GCF) can be used as markers of the local inflammatory periodontal burden in patients with HF.

Methods:
Medical and dental examinations were performed on patients with HF (n=41), following heart transplantation (post-HTx, n=40) and controls (n=32). Blood, saliva and GCF samples were taken to investigate markers of bone metabolism and inflammation.

Results:
Average New York Heart Association classification for HF was class III. Average time since HTx was 33.14 months. Overall periodontal diagnosis was more severe in patients with advanced HF and post-HTx versus controls (p<0.0001). Pro-inflammatory tumor necrosis factor-alpha (TNF-α) was higher in HF and HTx patients as compared to controls (p<0.05). Both, HF and HTx participants had higher levels of bone resorption marker C-terminal telopeptide and parathyroid hormone with subjects in the HF group having the highest serum levels of all groups (p≤0.05). In contrast, 25-VitD was lowest in patients with HF. The bone formation markers osteocalcin and procollagen-1 N-terminal peptide did not display differences between groups. Further, we found a significant correlation between beta-glucoronidase in saliva (r=0.4863, p<0.01) and interleukin-1b in saliva (r=0.4999, p<0.01) and GCF (r=0.5943, p<0.001) and the severity of periodontal disease.

Conclusion:
Patients with advanced HF exhibit more severe periodontal disease associated with increased bone turnover markers when compared to control patients. Further, periodontal disease severity was detectable in saliva and GCF making it a potential useful tool for identifying the need for periodontal treatment in patients with advanced HF.
Abstract 20107: Randomized Comparison of Personalized versus Standardized Substrate Modification During Catheter Ablation for Symptomatic Atrial Fibrillation
Authors: Kircher Simon , Arya Arash , Altmann David , Rolf Sascha , Bollmann Andreas , Sommer Philipp , Richter Sergio , Breithardt Ole , Dinov Borislav , Husser Daniela , Eitel Charlotte , Gaspar Thomas , Piorkowski Christopher , Hindricks Gerhard
Published: July 2021

Introduction:
Pulmonary vein (PV) isolation forms the cornerstone of any ablation procedure for atrial fibrillation (AF). There is, however, no uniform strategy how to detect and target left atrial (LA) arrhythmogenic substrate outside the PV antra. Fibrosis that corresponds well to LA low-voltage areas (LVAs) seems to play a key role in AF arrhythmogenesis and might therefore be a suitable target for additional substrate modification (SM).

Objective:
The purpose of this prospective randomized study was to compare a novel technique for SM based on ablation of potentially arrhythmogenic LA LVAs with a standard approach consisting of empiric LA linear ablation.

Methods:
Patients (pts) with symptomatic paroxysmal or persistent AF were randomized to standard (group 1) or personalized (group 2) SM. Circumferential PV isolation was the primary step in both groups. In group 1, pre-defined linear lesions were applied at the LA roof and bottom, respectively, and at the mitral isthmus only in pts with persistent AF. In group 2, targets for SM (i.e. LVAs) were identified by detailed bipolar voltage mapping (BVM) during sinus rhythm irrespective of AF type. Peak-to-peak electrogram amplitudes were defined as “normal” (> 0.5 mV), as “low voltages” (0.2 to 0.5 mV), or as “scar” (< 0.2 mV). LVAs were targeted by tissue homogenization and / or strategic linear lesions. The primary endpoint was freedom from any atrial arrhythmia (i.e. AF, atrial flutter, or atrial tachycardia) > 30 seconds off antiarrhythmic drugs on serial 7-d-Holter ECG recordings after a follow-up period of 12 months.

Results:
In total, 124 ablation-naïve pts (mean age 63 ± 9 years, 62 % male, 49 % with persistent AF) were enrolled in this study. LVAs were present in 18 % of pts with paroxysmal and in 41 % of pts with persistent AF (p<0.05). At the end of the follow-up period, 25 out of 59 pts (42 %) in the conventional group were free from arrhythmia recurrence as compared to 40 out of 59 pts (68 %) in the BVM-guided group (unadjusted log rank p = 0.003).

Conclusion:
Personalized SM guided by endocardial BVM is associated with a higher success rate compared to a conventional approach applying empirical SM based on AF phenotype.
Abstract 20126: Associations of Known Complications of Transcatheter Implantation of Balloon-expandable Edwards-Sapien XT Aortic Valves With Peri-procedural Mortality - An Insight From the 2014-2015 Reports From the FDA MAUDE Database
Authors: Ranjan Pragya , Chatterjee Saurav , Gupta Deepansh , Sardar Partha , Giri Jay , Bhinder Jasjit , Mukherjee Debabrata , Correa Ashish , Kumbhani Dharam J
Published: July 2021

Background:
Transcatheter implantation of aortic valves (TAVR) has revolutionized the management of severe aortic stenosis. However, specific complications have been noted with the valves. Details of such were sought from the US Food and Drug Administration (FDA) maintained MAUDE database which houses medical device reports submitted to the FDA by mandatory reporters (manufacturers, importers and device user facilities) and voluntary reporters such as health care professionals, patients and consumers.

Methods:
A detailed search was conducted in PubMed, Cochrane Library, EMBASE and CINAHL to identify adverse events reported with the implantation of the Edwards-Sapien XT valves. Then the FDA MAUDE database was queried from June 2014 to May 2015 to identify prevalence of the same complications as reported to the FDA. Individual patient reports were identified and relevant data on such complications were abstracted. Finally, mortality outcomes from such patients were abstracted, and associations of these for each individual reported complication were identified in a multivariate logistic regression model.

Results:
FDA MAUDE revealed 730 unique reports of complications with the first- generation Edwards-Sapien valves. A total of 106 patients died peri-procedurally. The complications most strongly associated with peri-procedural mortality were development of peri-procedural vascular complications, need for permanent pacemaker, renal failure, atrial fibrillation, stroke, need for surgical valve implantation and need for valve in valve procedure. (Table 1)

Conclusions:
Specific complications with the new Edwards XT valves were strongly associated with mortality, and focused strategies to mitigate these complications may improve outcomes with future generations of this exciting new technology.
Abstract 9781: Deletion of Prolyl Hydroxylase Domain Protein 2 in Myeloid Lineage suppressed Experimental Abdominal Aortic Aneurysm via NF-κB Inactivation
Authors: Tokunou Tomotake , Sankoda Chikahiro , Watanabe Aya , Takahara Yusuke , Kojima Hiroshi , Kitamoto Shiro , Ichiki Toshihiro , Sunagawa Kenji
Published: July 2021

Background:
Macrophage migration to the vessels is important for vascular inflammation and induces vascular degenerative diseases. Macrophages secrete matrix metalloprotainases (MMPs), which activate many cytokines and digest extracellular matrix of aorta. MMPs play an important role in the progression of aortic aneurysm. We previously reported that non-specific prolyl hydroxylase domain protein (PHD) inhibitor, Cobalt chloride (CoCl2), suppressed MMP-2 and -9 expression and attenuated experimental abdominal aortic aneurysm (AAA) formation in mice. In this report we investigated the myeloid specific PHD2 knockout effect on MMPs expression and aneurysm formation.

Methods:
Myeloid specific PHD2 conditional knockout (MyPHD2KO) mice were generated. Experimental AAA was induced by periaortic application of Calcium chloride (CaCl2) for 6 weeks. In vitro Lipopolysaccharide (LPS, 100ng/ml) was used to induce MMP-2 and MMP-9 expression with peritoneal macrophages. MMPs mRNA, protein expression and protein activity were analyzed by qRT-PCR, Western blot analysis and Zymography, respectively. ELISA-based NF-κB p65 Transcription Factor Assay was used to examine NF-κB p65 binding activity with consensus DNA binding site.

Results:
CaCl2-induced AAA was suppressed with MyPHD2KO mice (max diameter of aneurysm: 1.03mm±0.14mm in MyPHD2KO group, 1.63mm±0.34mm in Control AAA group, p<0.01). In peritoneal macrophages CoCl2 reduced LPS-induced MMP-2 and MMP-9 mRNA and protein expression. PHD2 deletion in peritoneal macrophages from MyPHD2KO mice also suppressed LPS-induced MMP-2 and MMP-9 mRNA, protein expression and activity. PHD2 deletion suppressed LPS-induced NF-κB p65 phosphorylation via IκBα stabilization by Western blot analysis. NF-κB p65 binding activity was suppressed in MyPHD2KO macrophages (p<0.01 vs control).

Conclusion:
Deletion of PHD2 in myeloid lineage attenuated MMPs expression by NF-κB inactivation and suppressed AAA formation. PHD2 in macrophage may be a novel target for cardiovascular disease treatment.
Abstract 9793: Pcsk9 Loss-of-function Variants, Low-density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data From the REGARDS Study and CHARGE Consortium
Authors: Kent Shia T , Rosenson Robert S , Avery Christy L , Correa Adolfo , Cummings Steven R , Cupples Adrienne , Cushman Mary , Evans Daniel S , Gudnason Vilmundur , Harris Tamara B , Howard George , Irvin Marguerite R , Judd Suzanne E , Jukema J. W , Lange Leslie , Levitan Emily B , Li Xiaohui , Liu Yongmei , Postmus Iris , Psaty Bruce M , Rotter Jerome I , Safford Monika M , Sitlani Colleen M , Smith Albert V , Stewart James D , Trompet Stella , Sun Fangui , Vasan Ramachandran S , Woolley J M , Whitsel Eric A , Wiggins Keri L , Wilson James G , Muntner Paul
Published: July 2021

Introduction:
PCSK9 loss-of-function variants are associated with reduced low-density lipoprotein cholesterol (LDL-C) concentrations. Genetic association studies of PCSK9 loss-of-function variants allow for the examination of the effects of lifetime low LDL-C on cardiovascular outcomes.

Hypothesis:
PCSK9 loss-of-function variants are associated with lower concentrations of LDL-C and reduced risk of coronary heart disease (CHD) and stroke.

Methods:
We studied the association of PCSK9 loss-of-function Y142X and C679X nonsense variants (n=366; 2.1%) in 17,459 African Americans (AAs) and R46L missense variants (n=962; 3.1%) in 31,469 whites with LDL-C, CHD and stroke in the US-based REasons for Geographic And Racial Difference in Stroke (REGARDS) study and 8 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We combined multivariable adjusted differences in LDL-C between participants with and without PCSK9 variants across studies using inverse-variance weighted fixed-effects models. We calculated unadjusted odds ratios (ORs) for associations between PCSK9 variants and incident CHD (851 events in AAs and 2,662 events in whites) and stroke (523 events in AAs and 1,660 events in whites) using pooled Mantel-Haenszel estimates with continuity correction factors.

Results:
In the pooled cohorts, PCSK9 variants were associated with 36 mg/dL (95% confidence interval [CI]: 31, 40) lower LDL-C in AAs and 13 mg/dL (95% CI: 11, 16) lower LDL-C in whites. PCSK9 variants were associated with a pooled OR for CHD of 0.51 (95% CI: 0.28, 0.92) in AAs and 0.82 (95% CI: 0.63, 1.06) in whites. PCSK9 variants were not associated with incident stroke (OR=0.84 [95% CI: 0.48, 1.47] in AAs and OR=1.06 [95% CI: 0.80, 1.41] in whites).

Conclusions:
These results provide evidence that PCSK9 variants are associated with lifelong reduction in LDL-C and may lead to lower CHD risk, but no effect on stroke risk.
Abstract 9905: Myeloid Cell Derived Leucine Rich α2 Glycoprotein Attenuates Adverse Cardiac Remodeling After Myocardial Infarction
Authors: Kumagai Shohei , Nakayama Hiroyuki , Fujimoto Minoru , Honda Hiromi , Serada Satoshi , Kasai Atsushi , Obana Masanori , Sakata Yasushi , Sawa Yoshiki , Naka Tetsuji , Fujio Yasushi
Published: July 2021

Background:
Leucine rich α2 glycoprotein (LRG), a member of the leucine-rich repeat family, was isolated from human plasma. Recently, LRG has been identified as a novel serum biomarker for various inflammatory diseases. It was also reported that serum LRG concentrations was strongly correlated with B-type natriuretic peptide in patients with heart failure. However, its pathophysiological roles in hearts after myocardial infarction (MI) remain to be elucidated.

Objective:
To determine the functional roles of LRG in cardiac remodeling after MI.

Methods and Results:
Murine MI was generated by ligating the left coronary artery. The expression of LRG was increased in hearts after MI. Immunofluorescence microscopic and flow cytometric analyses revealed that LRG was mainly produced by CD11b-positive myeloid cells in post-infarct myocardium. To elucidate pathophysiological roles of LRG in heart, we generated MI in wild-type (WT) and LRG-knockout (KO) mice. At day 14 after MI, cardiac fibrosis and dysfunction were aggravated in KO mice compared to WT mice (fibrotic area/ LV area: WT: 34.1 ± 7.2%, KO: 46.5 ± 12.8% n=10-16, p<0.01) (fractional shortening: WT: 34.8±7.1%, KO: 24.3±7.0%, n=6-9, p<0.01). Immunohistochemical analysis demonstrated that CD31-positive vessel density decreased at border zone in KO mice compared to WT mice 14 days after MI (vessel density: WT: 2740±190/mm2, KO: 2183±293/mm2 n=10-16, p<0.01). We explored the mechanism of LRG-mediated angiogenesis in post-infarct myocardium, and found that the activation of smad1/5/8, a pro-angiogenic signaling pathway, was attenuated in KO mice. Accompanied by impaired angiogenesis, cardiomyocytes apoptosis was increased in KO mice compared to WT mice at subacute phase after MI. Finally, bone marrow chimera experiments showed that bone marrow cells-derived LRG rescued adverse cardiac remodeling in KO mice, accompanied by restoration of capillary density.

Conclusion:
LRG was mainly produced by heart-infiltrated myeloid cells, and suppressed adverse cardiac remodeling after MI through enhanced angiogenesis. In this study, LRG was defined as a novel cardioprotective factor. Thus, LRG could be not only a serum biomarker but also a therapeutic target in cardiovascular diseases.
Abstract 9947: Predictors of Left Ventricular Dysfunction After Aortic Valve Replacement in Patients With Mixed Aortic Valve Disease
Authors: Egbe Alexander , Poterucha Joeseph , Warnes Carole
Published: July 2021

Objectives:
Predictors of left ventricular dysfunction (LVD) after aortic valve replacement (AVR) in mixed aortic valve disease (MAVD) have not been studied. Objective was to determine prevalence and predictors of early and late LVD at 1 and 5 years post-AVR.

Methods:
Retrospective review of 247 patients (Age 63±8 years, males 81%) with moderate/severe MAVD who underwent AVR at the Mayo Clinic from 1994-2013. Only patients with follow-up data at 1 year post AVR were included (n=239). Cohort divided into 3 groups based on data collected prior to AVR, 1 and 5 years post AVR. LVD was defined as ejection fraction <50%.

Results:
LVD was present in 11/239 at baseline. At 1-year post AVR, 181 had normal EF (group 1) while 58/239 (24%) had early LVD (group 2). Predictors of LVD were atrial fibrillation (hazard ratio [HR] 1.83 confidence interval [CI] 1.59-1.98, p=0.001), age >70 years (HR: 3.12, CI: 2.33-4.18, p= <0.0001), CABG (HR: 2.17, CI: 2.24-5.93, p= <0.0001), and severe MAVD pre-operatively (HR: 2.87, CI: 2.33-3.17, p= 0.01), and hypertension (HR: 1.83, CI: 1.35-2.46, p= <0.0001). Prevalence of late LVD was 24% (47/197-group 3) and LVMI at 1 year post AVR was predictive of late LVD (HR 1.65, CI 1.11-3.8 per 10 g/ m
2
increment, p= 0.04)). Group 2 had less reverse LV remodeling compared to group 1 at 1 year post AVR (142±39 vs 129±42 g/ m
2
, p=0.02).

Conclusions:
Risk of LVD was significant even in subset of patients with moderate MAVD. Risk stratification of MAVD should be based on both clinical and echocardiographic parameters. Our data suggest earlier surgical intervention may be required in the MAVD population to prevent postoperative LVD but further studies are needed.

Figure legend:
FU: follow up
Abstract 9950: Patients With Depressive Symptoms Experienced Substantial Adverse Cardiac Remodeling After Myocardial Infarction
Authors: Ipek Gokturk , Heydari Bobak , Abdullah Shuaib , Mandry Damien , Feng Jiazhuo H , Antman Elliot , Jerosh-Herold Micheal , Kwong Raymond Y
Published: July 2021

Background:
Mechanisms underlying post-MI depression and cardiac events in CAD patients remain poorly understood. The OMEGA-REMODEL Study is a randomized double-blind trial assessing for any benefical effects of post-MI LV remodeling by high-dose Omega-3 fatty acids (n-3 FAs). As a post-hoc analysis, we tested the hypothesis that patients with higher depression scores experienced more severe adverse post-MI remodeling.

Methods:
358 patients with acute MI were randomized to placebo or 4g/d n-3 FAs with 2-4 weeks post-MI. All patients underwent Hamilton Depression Scale, cardiac MRI, inflammatory biomarkers, and red cell n-3 index at baseline and after 6 months of study drug. Patients were stratified by median depression score as DEP and non-DEP.

Results:
Demographics and baseline LV measurements are shown in Table 1. N-3 FAs assignment resulted in significant improvement in LVESV compared to placebo. Compared to patients without DEP at baseline, those with DEP had slightly smaller LVEDV but similar LVESV, LVEF and infarct size. However, patients with DEP experienced marked expansion of LVEDV and LVESV compared to patients without DEP during the 6 months study period (P=0.007 and 0.02, respectively). N-3 FAs appeared to benefit LV remodeling of patients with or without DEP. Inflammatory markers did not correlate with the severity of the adverse LV remodeling.

Conclusion:
In conclusion, patients with DEP were substantially more likely to experience adverse cardiac remodeling which may account for the adverse cardiac outcomes of post MI depression.

Table 1:
Baseline Features and Changes in Cardiac Parameters
Abstract 9955: Outcomes of Catheter Ablation of Atrial Fibrillation in Hypertrophic Cardiomyopathy Patients - A Pooled Analysis
Authors: Yarlagadda Vivek , Kanmanthareddy Arun , Dherange Parinita A , Agasthi Pradyumna , Mahankhali Sridhar Arun Raghav , Bommana Sudharani , Atkins Donita , Natale Andrea , Di Biase Luigi , Lakkireddy Dhanunjaya , Reddy Madhu
Published: July 2021

Objectives:
Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM.) Aggressive rhythm control is recommended for this group of patients and radiofrequency catheter ablation is emerging as a frontline strategy. This pooled analysis aims to study the efficacy and outcomes of AF ablation in HCM patients

Methods:
PubMed, EMBASE and Google Scholar databases were searched to identify all studies describing the outcomes of catheter ablation of AF in HCM. Data from identified studies was extracted and pooled analysis was carried out using CMA 2 software. Pooled adjusted procedure duration and incident rates of recurrence and adverse events were calculated using random effects model.

Results:
A total of 11 studies with 384 patients were included in this study. For the index procedure, mean procedural time, radio frequency ablation and fluoroscopy times were 207.3 minutes, 39.7 minutes and 62.4 minutes respectively. The adjusted incidence of major ablation-related complications (death, stroke, transient ischemic attack, peripheral embolism, cardiac tamponade or perforation, valvular damage, arteriovenous fistula requiring surgical intervention, and a large vascular access site hematoma resulting in a drop of hemoglobin level by 2 g/dL) was 4 per 100 procedures (95% CI 2.1 - 7.5%). The recurrence of AF after index ablation during the mean follow up period of 14.5 months occurred in 58% (95% CI 50 -66%) of the patients (Figure1).

Conclusion:
The results of our analysis suggest that there is a high rate of recurrence of AF in HCM patients who undergo single AF ablation. The risk of complications with AF ablation appears to be low in this group of patients. Further studies are needed to assess the impact of multiple ablations on long term outcomes in these patients.
Abstract 9958: Fitness in Young Adulthood is Independently Associated With Improved Survival and Cardiovascular Risk: The CARDIA study
Authors: Shah Ravi , Murthy Venkatesh , Colangelo Laura , Reis Jared , Venkatesh-Ambale Bharath , Sharma Ravi , Abbasi Siddique , Goff David , Carr J. Jeffrey , Rana Jamal , Terry James , Bouchard Claude , Sarzynski Mark , Eisman Aaron , Neilan Tomas , Das Saumya , Jerosch-Herold Michael , Lewis Gregory , Lima Joao
Published: July 2021

Introduction:
Though cardiorespiratory fitness (CRF) is a well-established prognostic marker in older adults, the relationship between changes in CRF during early adulthood and long-term cardiovascular structure, function, and events remain unknown.

Hypothesis:
CRF and its change over time in young adults is associated with long-term outcome and cardiovascular disease (CVD).

Methods:
4,872 American adults age 18-30 years underwent treadmill exercise testing at a baseline study visit in 1985-1986, and 2,472 individuals who underwent repeat treadmill testing 7 years later in CARDIA. Participants were followed for a median of 26.9 years, with assessment of obesity, echocardiographic left ventricular (LV) mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Incident CVD (cardiovascular death, heart failure, myocardial infarction, peripheral artery disease and stroke) and all-cause mortality were uniformly adjudicated.

Results:
From 4,872 individuals, 273 (5.6%) died and 193 (4%) experienced CVD events at a median 26.9 year follow-up. After full adjustment, each additional minute of baseline exercise test duration was associated with a 13% lower hazard of death (hazard ratio HR 0.87, 95% CI 0.81-0.92, P<0.0001) and a 9% lower hazard of CVD (HR 0.91, 95% CI 0.84-0.98, P=0.008). Higher baseline fitness was associated with decreased risk of LV hypertrophy (P=0.009) and higher global longitudinal strain (P<0.0001) at Year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by Year 7 was associated with a 20% increased hazard of death and CVD, along with a greater probability of LV hypertrophy and more impaired strain. There was no association between change in fitness and CAC.

Conclusions:
Higher fitness at baseline and improvement in fitness early in adulthood are favorably associated with CVD and mortality risk. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction, but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.
Abstract 38: Tandem Effects of Specific Foods on Cardiometabolic Risk within the Context of Overall Dietary Patterns: A Meta-analysis of Randomized Controlled Feeding Trials
Authors: Singh Gitanjali M , Otto Marcia , Mozaffarian Dariush
Published: July 2021

Background:
Cardiometabolic (CMB) risk factors are major mediators of the effects of diet on health. Multiple foods are often consumed in tandem, yet CMB effects of individual dietary factors are often studied in isolation, leading to estimates that may not represent true effects as part of diet patterns.

Objective:
To quantify the effects of major foods (fruits, vegetables, nuts/seeds, whole grains, fish) and dietary fiber, when consumed within the context of overall diet patterns, on systolic BP, serum lipids, and glucose-insulin homeostasis.

Methods:
PubMed was searched through Oct 2015 to identify randomized controlled feeding studies evaluating effects of major dietary patterns on CMB factors. We included trials evaluating major dietary patterns including fruits, vegetables, nuts/seeds, whole grains, fish, and dietary fiber as major components and evaluating effects on systolic BP, serum lipids (total cholesterol, LDL-C, HDL-C, or triglycerides), or markers of glucose-insulin homeostasis (fasting plasma glucose, HbA1c, postprandial glucose, or fasting insulin). Multivariate metaregression was used to estimate food-specific effects on CMB factors.

Results:
Among 15 included trials, diet-pattern related decreases in SBP ranged from -2.2 to -9.5 mmHg; and in LDL-C, from -5.0 to -14.7 mg/dL. Each specific food had different, independent, and additive effects on these risk factors (
Figure
). Results for measures of glucose-insulin homeostasis are in progress.

Conclusions:
Each of these foods independently influences major CMB risk factors, even when consumed in tandem as part of overall diet patterns
.
Such quantification more accurately reflects the complementary effects of diverse dietary components and highlights the importance of integrated approaches to investigating dietary factors and implementing relevant dietary policies.