bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11124: Mitral Annular Calcification Mitral Stenosis: Obstruction is in the Tunnel
Authors: Friend Evan , Murthy Kinnari , Qamruddin Salima , Pressman Gregg S
Published: March 2022

Background:
Mitral annular calcification (MAC) is an increasingly encountered cause of mitral stenosis. As opposed to rheumatic disease, in MAC the commissures are typically open. In some cases the leaflet tips remain freely mobile while in others they are restricted. We sought to determine if mean mitral valve gradient (MVG) is associated with the minimal area in the MAC tunnel or the area at the leaflet tips.

Methods:
High quality 3D TEE datasets were acquired in 10 subjects with severe bulky MAC. Custom 2D cut planes were created at the mitral valve inlet, the narrowest portion of the MAC tunnel, and at the leaflet tips (figure 1), and compared with MVG by continuous wave Doppler.

Results:
Area at the annular inlet ranged from 5.4 - 11.0 cm
2
(mean 8.2). The smallest area within the tunnel ranged from 1.3 - 4.0 cm
2
(mean 2.4) while the smallest area at the leaflet tips ranged from 1.0 - 2.6 cm
2
(mean 1.6). MVG ranged from 3 - 14 (mean 8) mm Hg. As annular inlet area decreased MVG increased (r
2
= 0.49, p = 0.024). Similarly, as minimum tunnel area decreased MVG increased (r
2
= 0.54, p = 0.015; figure 2). There was a no significant relation between MVG and smallest leaflet area (r
2
= 0.17, p = 0.23). There was also no association between degree or distribution of MAC, and MVG or smallest tunnel area.

Conclusions:
In subjects with severe MAC and a resting gradient across the valve, obstruction to flow occurs at the annular inlet and within the calcium tunnel. In contrast to rheumatic mitral stenosis, valve area at the leaflet tips does not appear to determine the MVG.
Abstract 11129: Long-Term Success Rate of Intramural PVC Ablation
Authors: Mohanty Sanghamitra , Burkhardt John , TRIVEDI CHINTAN G , Zagrodzky William , Della Rocca Domenico G , Gianni Carola , MacDonald Bryan , Mayedo Angel , Bassiouny Mohamed , Romero Jorge , Gallinghouse G , Horton Rodney , Di Biase Luigi , Al-ahmad Amin , Natale Andrea
Published: March 2022

Introduction:
Intramural PVCs are identified by equal but not remarkably early activation on at least two separate sites. The site of origin of these foci is typically determined by a deductive approach using extensive mapping in the surrounding areas. Ablation of the intramural VT is particularly challenging, since conventional ablation strategies often fail to obtain transmural lesion formation. We report the long-term success rate of ablation of the intramural PVCs at our center.

Methods:
Consecutive patients undergoing VT ablation at our center were screened and 73 patients with intramural PVCs identified by activation mapping and pace mapping were included in the analysis. Pace-mapping was performed at a pacing cycle length equal to the coupling interval of the spontaneous PVCs. If these PVCs could not be eliminated by conventional ablation, bipolar ablation or ablation from multiple sides or ablation using half-normal saline (HNS) was performed. Standardized RF power settings (up to 40W) were used during the procedure. Ablation was performed using 4-mm irrigated tip catheter guided by 3-D mapping system and intra-cardiac echocardiography. Patients were followed with remote monitoring as well as ICD interrogations and office visits every 3 months for 3 years.

Results:
A total of 73 patients were included in the analysis (mean age 56.2±8.6 years, 69.8% male, LVEF 54±12%). The intramural focus was effectively ablated by bipolar ablation or ablation from multiple sides in 51 (69.8%) and with the use of HNS in the remaining 22 patients. Median RF time was 11.14±8.7 minutes. Acute success (non-inducibility of the VT) was achieved in 71 (97.2%) patients. At 3 years follow-up, 66 (90.4%) remained arrhythmia-free.

Conclusion:
Intramural PVCs could be successfully ablated using bipolar or multiple-side ablations or utilizing half-normal saline with high long-term success rate.
Abstract 11131: Discharge on Sacubitril/Valsartan vs. ACEi/ARB in Older Patients with HFrEF: A Decision Analysis Approach
Authors: Zipkin Ronnie , Barnes J. Aaron , Tosteson Anna , Gaziano Thomas A , Gilstrap Lauren
Published: March 2022

Introduction:
Based on the results of PARADIGM-HF and PIONEER-HF, angiotensin-receptor neprilysin inhibitors (ARNI) offer improved survival and lower readmission rates for HFrEF compared to angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). However, there is concern that increased hypotension and higher drug costs may limit the effectiveness of ARNIs in clinical practice, especially among older adults with Part D prescription coverage. The aim of this study is to use decision analytic modeling to estimate the association between discharge on ARNI vs. ACEi/ARB and patient outcomes, and then determine if it varies by age.

Methods:
We then used a 2-state absorbing Markov chain model with a 1-month cycle length to simulate 5-year survival for patients discharged on ARNI or ACEi/ARB, accounting for the risks of death and readmission, estimated from trials, as well as the risk of in-hospital mortality, drug switching, and discontinuation, estimated from Medicare claims data. In the model, the weighted averages for mortality and readmission reduction were estimated published risk reductions from the PIONEER-HF trials (first two months) and PARADIGM-HF (subsequent 8 months) trials.

Results:
Across all age groups, patients discharged on ARNI had higher 5-year survival compared to patients discharged on ACEi/ARB (
Table 1
). Moreover, the absolute and relative benefit of ARNI over ACEi/ARB, even after accounting for drug discontinuation and switching, was similar across age groups. The number needed to treat (NNT) with ARNI rather than ACEi/ARB to prevent 1 death over 5 years ranged from 56-63.

Conclusions:
There is a small, but clinically significant, survival benefit to discharge on ARNI vs. ACEi/ARB across all age groups, even after accounting for drug switching and discontinuation. Additional work is needed to determine if there is additional heterogeneity of treatment effect in subgroups of high-risk, older adults.
Abstract 11136: Obstructive Sleep Apnea in Aortic Dissection
Authors: Friend Evan , Murthy Kinnari , Leinveber Pavel , Svatikova Anna , Hochhold John , Pressman Gregg S
Published: March 2022

Background:
Obstructive sleep apnea (OSA) imposes an afterload burden on the left ventricle and increases the pressure gradient across the intrathoracic aorta. This might increase the likelihood of aortic dissection (AD). We hypothesized that patients with acute AD would have a high prevalence of previously undiagnosed OSA and a largely nocturnal presentation.

Methods:
40 consecutive, consenting subjects with acute AD who survived to hospital discharge were collected from 4 institutions. Mean age was 57 (range 28-75), 24 were male. 25 had type A dissection and 15 type B. 37 completed the modified Berlin Questionnaire and 30 had attended overnight polysomnography. Presenting CT scans had aortic diameter measured at a) the sinotubular junction b) ascending aorta c) origin of innominate d) mid-arch e) origin of left subclavian f) mid-descending aorta g) level of diaphragm; CT scans at 3 months were available in 24 subjects.

Results:
AHI ranged from 0 - 89; prevalence of OSA (defined by apnea-hypopnea index [AHI] > 5) was 63%. There were no differences in aortic diameter at any level comparing OSA vs non-OSA, regardless of AHI cutoff (>5, >15, >30; figure). Over time aortic diameter decreased at the level of the sinotubular junction and ascending aorta (expected - due to surgery). Whether dissection occurred during overnight hours (10 PM - 7 AM) did not differ by presence/absence of OSA (regardless of AHI cutoff). In those with high-risk Berlin questionnaires (>=2 categories positive) 10/21 (48%) dissections occurred during sleeping hours vs 2/13 (15%) in low risk Berlin group (p = 0.08, Fisher’s exact test).

Conclusions:
Among patients with acute AD the prevalence of OSA was high. Aortic diameters, however, were not different according to level of AHI. Presence of OSA defined by polysomnography was not associated with a nocturnal presentation in this sample.
Abstract 11144: Mitral Valve Leaflet Strains Are Unphysiologically Altered After Mitraclip to Repair Functional Mitral Regurgitation
Authors: Lane Brooks A , Xu Dongyang , Padala Muralidhar
Published: March 2022

Introduction:
Transcatheter edge-to-edge repair (TEER) by approximating the leaflet edges with the MitraClip system (
Fig. A
) is rapidly gaining momentum as the primary therapy for repair of functional mitral regurgitation. Though effective acutely, the unphysiological mechanics that TEER imposes on the valve can be substantial and effect durability of the repair. In this study, we used stereo digital image correlation (sDIC) to quantify the leaflet strains that TEER imposes on the mitral valve in the repair of FMR.

Hypothesis:
TEER imposes an unphysiological diastolic and early systolic strain on the mitral valve leaflets, which may be associated with poor long-term outcomes.

Methods:
MVs with intact papillary muscles (PMs) were isolated from porcine hearts and mounted within an acrylic left ventricle chamber. A speckle pattern was imprinted on the valve leaflet surface and a sDIC system with two high-speed cameras imaging at 250 fps recorded synchronized image sequences upon pressurization of the chamber to 120 mm Hg in three different configurations: baseline/healthy, FMR/tethered valve configuration, and with TEER/MitraClip.

Results:
FMR configuration (
Fig. A2
) did not alter the peak systolic leaflet strains but elevated the diastolic leaflet strains. The time to peak strain was delayed as well in the FMR configuration. TEER reduced the overall systolic strains on the leaflet from the disease state, but the diastolic strains were further elevated compared to FMR condition. Sub-regional analysis depicted that the leaflet edge section where the TEER was applied was under constantly high strain throughout the cardiac cycle, without an unloading phase.

Conclusions:
TEER imposes a supraphysiological strain field on the mitral valve leaflet when used to repair FMR. The impact of such strains is not yet known, but may be associated with leaflet remodeling and the 2% of the procedures in which single leaflet detachment has been reported.
Abstract 11146: Cardiovascular Outcomes in Patients with Atrial Fibrillation Using Dronedarone and Non-Dronedarone Antiarrhythmic Drugs
Authors: Wu Victor Chien-Chia , Wang Chun-Li , Huang Yu-Chang , Tu Hui-Tzu , Huang Yu-Tung , Huang Chien-Hao , Chen Shao-Wei , Kuo Chang-Fu , Hung Kuo-Chun , Chang Shang-hung
Published: March 2022

Introduction:
Dronedarone was developed to improve outcomes in patients with atrial fibrillation (AF) compared with other antiarrhythmic drugs.

Hypothesis:
Dronedarone may offer better cardiovascular outcomes compared to non-dronedarone antiarrhythmic drugs.

Methods:
Taiwan National Health Insurance Research Database were retrieved between 2012-2017 for patients with AF. Patients not taking antiarrhythmic drugs, having history of bradycardia, heart block, heart failure admission, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up less than 3 months were excluded. Protocol 1, outcomes of patients with AF using dronedarone were compared to non-dronedarone antiarrhythmic drugs (amiodarone, propafenone, flecainide, sotalol). In Protocol 2, outcomes of patients with AF using dronedarone were compared to amiodarone, the most frequently used antiarrhythmic drug. Propensity score matching performed to reduce bias. Primary outcomes were acute myocardial infarction (AMI), ischemic stroke/systemic embolism (IS/SE), intracranial hemorrhage (ICH), major bleeding, cardiovascular death, and all-cause mortality. Secondary outcome was composite of AMI, ischemic stroke, and cardiovascular death (MACE).

Results:
In Protocol 1, after 1:3 matching, 2,032 dronedarone patients and 6,096 non-dronedarone patients were analyzed. Dronedarone was associated with significantly lower IS/SE (p=0.0033), ICH (p=0.0111), major bleeding (p=0.0230), cardiovascular death (p<0.0001), all-cause mortality (p<0.0001) and MACE (p<0.0001), without difference in AMI, compared to non-dronedarone. In Protocol 2, after 1:3 matching, 1,994 dronedarone patients and 5,982 amiodarone patients were analyzed. Dronedarone was associated with significantly lower IS/SE (p=0.0071), cardiovascular death (p<0.0001), all-cause mortality (p<0.0001), and MACE (p<0.0001), without differences in AMI, ICH, and major bleeding, compared to amiodarone. Use of anticoagulants and doses were similar between groups in both protocols.

Conclusions:
Dronedarone was associated with lower ischemic stroke/systemic embolism, cardiovascular death, all-cause mortality and MACE compared to non-dronedarone or directly to amiodarone.
Abstract 11149: Psychological Functioning and Parameters of Physiological Status in Youth with Fontan Circulation
Authors: Seivert Nicholas P , Park Christine , Rychik Jack , Goldberg David J , Demianczyk Abigail , Dodds Katie
Published: March 2022

Individuals with Fontan circulation (FC) are at high risk for physical and psychological problems. Many have poor growth, low weight gain, and low oxygen saturation (O2 sat). They also often have learning problems, inattention, and mood/anxiety disorders. Research on associations between these physical and mental challenges is limited. This study explores potential relations among these variables in a cohort with FC. We hypothesize that poorer growth, weight, and O2 sat are associated with greater problems with school, mood/anxiety, and inattention.

A team, including pediatric cardiologist, psychologist, and other medical specialties, evaluated participants in our FORWARD program, a dedicated multidisciplinary clinic for patients with FC. Data were extracted from medical records. Height, weight, and resting O2 sat were measured at the clinic visit. Patients completed a psychological screening questionnaire (BASC-3); scales selected for analyses were based on commonly recognized problems in FC: school (academic difficulties, negative school attitude), internalizing (mood/anxiety), and attention problems.

Sample consisted of 45 subjects; 53% male, 84% White, 81% had private health insurance. Plurality had hypoplastic left heart syndrome (47%). Mean age was 12.7
+
2.7 years, O2 sat 93.9
+
2.7 %, height z-score -0.58
+
1.42, and weight z-score -0.23
+
1.43. Mean values on all psychological measures were not indicative of problems. Height and weight were not related to psychological measures. O2 sat was inversely correlated with school problems (r= -.350, p= .018). Internalizing (r= .503, p< .001 ) and attention (r= .427, p= .002) problems were correlated with school problems. O2 sat, internalizing and attention problems were entered into a regression predicting school problems; the model explained 35.4% of the variance (p< .001).

School problems of individuals with FC are likely determined by both physical and psychological factors. In our relatively small and young cohort of patients, lower O2 sat may reflect relative overall FC unwellness, and is associated with greater psychological health challenges. Exploration of potential mechanisms underlying relations between physical and psychological health in those with FC is warranted.
Abstract 11150: Albuminuria in Heart Failure is More Strongly Associated with Markers of Congestion Than Renal Dysfunction
Authors: Boorsma Eva M , ter Maaten Jozine M , Damman Kevin , Pellicori Pierpaolo , Metra Marco , Dickstein Kenneth , van Veldhuisen Dirk J , Filippatos Gerasimos , Ng Leong , Anker Stefan D , Zannad Faiez , Cleland John , Voors Adriaan A , Emmens Lisa
Published: March 2022

Aims:
Albuminuria is common in patients with heart failure (HF) and associated with worse outcomes. It is unknown whether albuminuria only reflects renal dysfunction or whether it is related to the pathophysiology of HF. We therefore aimed to study the clinical characteristics and biomarkers associated with albuminuria in patients with new onset or worsening HF.

Methods and Results:
In the current analysis, we included 2315 patients from the index cohort of BIOSTAT-CHF who had a spot urinary sample available at baseline, and validated findings in 1431 patients from the independent BIOSTAT-CHF validation cohort.Micro-albuminuria and macro-albuminuria were defined as UACR >30 mg/gCr and >300 mg/gCr, respectively.In the index cohort 242 patients (10%) had macro- and 819 (35.4%) had micro-albuminuria. Patients with any albuminuria were more likely to be hospitalized, had a higher NYHA-class, more clinical signs of congestion and higher concentrations of biomarkers related to congestion, such as bio-ADM, CA-125 and NT pro-BNP. Moreover, they were more likely to have a history of diabetes mellitus (56.6% vs. 27.7% for macro-albuminuria vs. no albuminuria), hypertension and atrial fibrillation (all p<0.001). From multivariable linear regression the strongest predictor for log(UACR) was log NT pro-BNP (standardized B 0.41, 95% CI 0.32 - 0.50, p <0.001). This correlation was similar for all estimated glomerular filtration rates (p for interaction = 0.256). A dendrogram based on hierarchical clustering (Figure) demonstrates that UACR clusters with markers of congestion and HF disease severity and not with markers of renal (dys)function. The validation cohort yielded similar findings.

Conclusion:
In patients with HF, the presence of albuminuria was more strongly related to markers of congestion than markers of renal dysfunction. These data may suggest a direct relationship between congestion and albuminuria or a common underlying pathophysiological mechanism.
Abstract 11154: Cardioprotective Effects of Mtss1 Reduction Iin Dilated Cardiomyopathy
Authors: choe dongwook C , Brandimarto Jeffrey A , Petrenko Nataliya , Marti-pamies Ingrid , Burke Megan , Lv Wenjian , Day Sharlene , Musunuru Kiran , Wang Xiao , Cappola Thomas P
Published: March 2022

Introduction:
MTSS1 is an I-BAR protein that interacts with the actin cytoskeleton and the cell membrane and is speculated to play a role in cell motility, tumor metastasis, and cardiogenesis. Enhancer variants that reduce the expression of
MTSS1
in the human left ventricle have been associated with cardioprotective traits in genome-wide association studies. However, the effect of MTSS1 downregulation on the development of heart disease has not been studied in experimental models. Here we tested the hypothesis that reduction of MTSS1 protects against dilated cardiomyopathy (DCM)
in vitro
and
in vivo
.

Methods:
We used CRISPR-Cas9 to knock out
MTSS1
in induced pluripotent stem cells (iPSCs) harboring pathogenic variants from patients with severe DCM. DCM iPSC lines with and without
MTSS1
were then differentiated into cardiomyocytes and phenotyped
in vitro
. A DCM mouse model containing a
TPM1
D230N transgene was crossed with a mouse model heterozygous for
Mtss1
knockout. Progeny from this F1 cross were assessed for differences in cardiac structure and function via echocardiography.

Results:
MTSS1
deletion restored the beta-adrenergic response in DCM iPSC cardiomyocytes. In parallel,
Mtss1
deletion partially rescued DCM-associated phenotypes including left ventricular dilation and reduced ejection fraction in mice.

Conclusions:
Our initial results suggest a causal link between MTSS1 reduction and cardioprotection in DCM. Inhibiting cardiac MTSS1 may hold therapeutic potential for DCM, though the cellular mechanisms through which MTSS1 affects cardiac phenotypes remain under investigation.
Abstract 11158: Clinical Impact of Concomitant MR Among Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Twing Aamir , Dickens Helena , Gokhale Sanket , Cho Nicole , Simon Erik , Slostad Brody D , Kansal Mayank M , Shroff Adhir R , Groves Elliott
Published: March 2022

Background:
Mitral regurgitation (MR) is seen in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). However, clinical outcomes in these patients have varied. The purpose of this study is to assess outcomes and changes in EF after TAVR in patients with concomitant MR.

Methods:
Retrospective chart review from March 2018-June 2020 identified all TAVR patients from the University of Illinois, Chicago. MR was assessed as none, mild, moderate, or severe regurgitation on baseline transthoracic echocardiogram. Patients were included if they demonstrated 6 or 12-month follow-up after valve replacement. Outcomes included all-cause mortality, major adverse cardiovascular events (MACE), clinically significant bleeding, and improvement in EF category, which included normal (50-70%), mildly (40-49%), moderately (30-39%), or severely (<30%) reduced.

Results:
118 patients (age 76±10 years, 79% male, 46% white) followed up at 6-months and 112 at 12-months. Of these, 33% had baseline MR with 79% being mild and 21% moderate. Patients with AS+MR were more likely to have atrial fibrillation (41.0 vs. 19.0%, p=0.01) and an EF<50% (33.3 vs. 8.9%, p=0.001) compared to those with AS only. After TAVR, patients with MR were more likely to show improvements in EF category at 6 months (19.4 vs. 5.5%, p=0.039, Fig. 1). In those with AS+MR vs. AS only, there were no differences in all-cause mortality (12.8 vs. 5.1%, p=0.14), MACE (17.9 vs. 8.9%, p=0.15), or bleeding (10.3 vs. 6.3%, p=0.45) at 6 months. There were also no differences in all-cause mortality (16.2 vs. 14.7%, p=0.83), MACE (24.3 vs. 20.0%, p=0.60), or bleeding (13.5 vs. 10.7%, p=0.66) at 12 months.

Conclusion:
At 6 and 12 months after TAVR, patients with AS+MR experienced similar clinical outcomes as compared to those with only AS. Patients with AS+MR were more likely to show increases in EF 6 months after valve replacement. Our results suggest that patients with AS+MR stand to benefit after TAVR.
Abstract 11161: Comparison of Percutaneous Mitral Valve Repair in Patients with Normal vs Severely Reduced Ejection Fraction
Authors: Voudris Konstantinos , Chiang Caleb , Kavinsky Clifford J , Suradi Hussam
Published: March 2022

Introduction:
Percutaneous mitral valve repair (PMVR) has been established as a suitable alternative to mitral valve surgery in patients with severe mitral regurgitation (MR). Patients with severely decreased ejection fraction (EF≤ 30%) constitute a higher risk group for adverse outcomes and peri-operative mortality.

Hypothesis:
We sought to examine the efficacy and safety of MitraClip implantation in severe heart failure patients in comparison to patients with preserved LV function.

Methods:
Single-center, retrospective study of patients undergoing PMVR between January 2015 and December 2020. All patients were followed up for 30 days. Baseline and procedural characteristics as well as short term outcomes of all-cause mortality, heart failure hospitalizations, stroke, new atrial fibrillation, new pacemaker placement, and improvement in MR severity ≥2 grades and NYHA class were assessed.

Results:
Among 86 patients undergoing PMVR, 26 had severely decreased EF. Patients with severely decreased EF were younger and more likely to have diabetes and mixed pathology MR. Additionally they received guideline directed medical therapy at higher rates. Characteristics of the population are shown in Table 1. At 30 days, no significant difference was observed between the two groups in regards to all-cause mortality, HF hospitalization, stroke, new atrial fibrillation, new pacemaker placement, and improvement in MR severity ≥2 grades and NYHA class.

Conclusions:
PMVR with the MitraClip system is feasible and a safe option for patients with MR and severely reduced EF.
Abstract 11163: Biomechanics of Left Ventricular Remodeling in a Chronic Swine Model of Myocardial Infarction
Authors: Corporan Daniella , Silverman Michael , Sreerangathama Suresh Kirthana , Xu Dongyang , Onohara Daisuke , Padala Muralidhar
Published: March 2022

Introduction:
Adverse left ventricular (LV) remodeling after a myocardial infarction (MI) is an insidious process whose severity predicts future decompensated heart failure, morbidity and mortality. Our understanding of LV remodeling has been extensive at the molecular level, but little is known of the biomechanical changes that occur as the LV remodels, dilates, thins, and potentially has rearranged myofibers. In this study, we developed a chronic swine model of post-MI remodeling and used cardiac MRI to assess biomechanics of the remodeling LV after 10 weeks of infarction.

Methods:
Fourteen Yorkshire swine (n=14) were induced percutaneously with an MI by acute thrombosis of the left circumflex artery with ethanol infusion (
Fig.A1-A2
), and the animals were survived. Echocardiography and MRI was performed at baseline and at 10 weeks to assess LV function and biomechanics, respectively. MRI was performed on a 3T Siemens scanner, with short axis CINE and tagged imaging (
Fig.A3-A4
). LV strain, twist and torsion from short-axis tagged images and compared between baseline and 10 week values.

Results:
Survival rate after the infarction was 85.71%. Ejection fraction reduced from 54.79±5.52% at baseline to 47.29±8.36% 10 weeks post-MI (p=0.023) (
Fig.A5
). LV end diastolic volume, end systolic volume and sphericity index were significantly elevated (
Fig.A6-A8
). Radial strain values showed an increasing trend at 10 weeks after an MI, compared to baseline values (
Fig.B3
). Circumferential strain values showed a decreasing trend by 10 weeks after MI compared to baseline values (
Fig.B4
). Both ventricular twist and torsion were reduced compared to baseline, but the trend was more evident with LV torsion (
Fig.B5-B6
)
.

Conclusions:
After an MI of the postero-lateral wall, reduced ejection fraction and dilatation were observed as expected. LV radial strain was increased but circumferential strain, twist, and torsion of the left ventricle were significantly diminished.
Abstract 11165: Stimulated Release of Apoptosis- Induced Endothelial Microparticles in Patients with Diabetes and Coronary Artery Disease
Authors: Marei Isra , Omar Chidiac , Thomas Binitha , Muhammed Jameesh , Jayyousi Amin , Al suwaidi Jassim M , Abi Khalil Charbel
Published: March 2022

Introduction:
High endothelial microparticles (EMPs) levels could be used as a marker of vascular dysfunction.

Hypothesis:
The release of EMPs with apoptotic characteristics in the blood of patients with diabetes is different according to the presence of CAD, and further distinct between chronic CAD and ACS.

Methods:
A total of 80 participants were recruited and equally classified as: 1) healthy participants without diabetes, 2) healthy diabetics without micro or macro-vascular complications, 3) participants with T2D and chronic CAD, and 4) participants with T2D and ACS. MPs were isolated using ExoQuick-LP
TM
and analysed using flow cytometry of CD42 and CD31. CD62E was used to determine the apoptotic/activation state of the EMPs. MP content was extracted and profiled using angiogenesis array (R&D systems).

Results:
Mean age of participants was 56 ±10. Levels of CD42- CD31+ EMPs were significantly increased in diabetics with acute ACS (257.5±35.58) when compared to healthy subjects (105.7±12.96, p<0.01). There was no significant difference when comparing diabetics, with and without chronic CAD. The ratio of CD42-CD62+/ CD42-CD31+ EMPs was reduced in all diabetic groups, with further reduction in ACS when compared to chronic CAD, reflecting a release by apoptotic endothelial cells. The angiogenic content of the full population of MPs was analysed and revealed a significant differential expression of 5 factors in patients with ACS and diabetes: TGF-β1, PD-ECGF, platelet factor 4, serpin E1 and thrombospondin 1 (Figure 1). Ingenuity Pathway Analysis revealed of those 5 differentially expressed molecules, mainly TGF-β1, causes an inhibition of key pathways involved in normal endothelial function.

Conclusions:
Our data showed that the release of apoptosis-induced EMPs is increased in diabetes, irrespective of the presence of CAD, ACS patients having the highest levels. The protein contents of MPs interact in networks that are indicative of vascular dysfunction.
Abstract 11166: Can Claims Diagnoses Accurately Identify Heart Failure with Reduced and Preserved Ejection Fraction in Medicare Data?
Authors: Bates Benjamin , Akhabue Ehimare , Mukherjee Abhigyan , Nahass Meghan , Hiltner Emily P , Rock Joanna , Wilton Brandon , Dave Chintan , Setoguchi Soko
Published: March 2022

Background:
Medicare claims data have been widely used to describe the management and outcomes of patients with heart failure (HF). While the management of HFrEF vs HFpEF differs, the usefulness of ICD10 codes to differentiate HFrEF and HFpEF in Medicare data is not well characterized. Thus, we assessed if ICD10 codes can accurately identify HFrEF and HFpEF in Medicare data.

Methods:
Among 314,221 Medicare patients hospitalized for HF (defined as primary or secondary ICD10 I50.x) between 10/2015 and 12/2017, we randomly sampled 200 charts in a 1:1:2 ratio for systolic dysfunction (I50.2), diastolic dysfunction (I50.3), and other I50.x HF. Cardiology trained physicians extracted and adjudicated clinical information. We calculated positive predictive values (PPV) with 95% confidence interval (CI) of the ICD10 codes for HFrEF and HFpEF. HFrEF was assessed using varying ejection fraction (EF) cut-offs of 40% and 50% or in combination with qualitative EF assessment.

Results:
Among the 314,221 HF patients, 80% had codes for systolic/diastolic dysfunction (I50.2 or 3) and 20% had codes for combined dysfunction or unspecified HF. The 200-chart-validation-sample (mean age 81, 43% male and 90% white) included 50 systolic (I50.2), 50 diastolic (I50.3), 47 combined (I50.4) and 53 unspecified HF (I50.9) patients. EF was recorded in ≥80% of patients with systolic, diastolic, and combined dysfunction. For systolic HF code, the PPV for HFrEF was 80% and 92% using EF≤40% and ≤50%, respectfully. For diastolic HF code, the PPV for HFpEF was 96% (Table). The ICD10 code for combined or unspecified HF did not predict either HFrEF or HFpEF well.

Conclusion:
ICD10 codes that specify systolic or diastolic HF were used in 80% of hospitalized HF patients, had EF recorded in ≥80% of patients, and predicted reduced and preserved EF with high validity. Specific ICD10 HF codes alone may be useful in identifying populations with HFrEF or HFpEF in hospitalized Medicare patients.
Abstract 11167: Prevalent Locations of Left Atrial Scar in Patients with Non-Paroxysmal Atrial Fibrillation: A Single-Center Experience
Authors: Mohanty Sanghamitra , TRIVEDI CHINTAN G , Della Rocca Domenico G , Zagrodzky William , Gianni Carola , Mayedo Angel , MacDonald Bryan , Burkhardt John , Gallinghouse G , Al-ahmad Amin , Horton Rodney , Di Biase Luigi , Natale Andrea
Published: March 2022

Introduction:
Left atrial (LA) scar, identified by bipolar voltage mapping, is a frequent finding in patients with non-paroxysmal atrial fibrillation (NPAF). We evaluated the most common sites of scar formation in the LA in a series of NPAF patients.

Methods:
Consecutive NPAF patients undergoing their first catheter ablation at our center were included in this analysis. Voltage mapping was performed in sinus rhythm (SR) using a 3D electro-anatomic mapping system and a 10-pole circular mapping catheter. The LA was divided into following regions: septum, posterior wall, lateral wall, anterior wall and roof. The threshold for low voltage was <0.5 mV (with a color range setting 0.2-0.5 mV).

Results:
A total of 359 NPAF (224, 62.4% persistent AF) patients undergoing their first ablation procedure with voltage mapping performed in SR were included in this study. Mean number of points taken to map the scar was 281.2±96.3. Low voltage area was detected in 209/359 (58%) cases; 108 (48.62%) persistent AF, 101(74.8%) long-standing persistent AF, p<0.001). The scarring was observed to be located in the anterior septum in 98 (46.9%) and posterior wall of the LA in 136 (65%) patients (FIGURE)

Conclusion:
In the NPAF population, LA scar was detected in significantly less number of persistent AF patients. Scars were mostly located in the posterior wall of left atrium followed by the antero-septum region. Characterization of the LA scars would be helpful in optimizing the ablation targets.
Abstract 11170: In an Aortic System of Care Model, Adherence to Guideline Based Care is Hampered by Gaps in the Collection, Reporting, and Communication of Echocardiogram Data
Authors: Gordon Lucia , Rogers Terreal , Solsbery Laney , Wirtz Katy , Scharnott Michelle , Myers Gary W
Published: March 2022

Introduction:
Aortic Stenosis (AS) is one of the most common and serious valve diseases, affecting 5% of Americans age 65 or older. Currently, there lacks a national system of care addressing the AS care continuum. The American Heart Association (AHA) has a history of success in systems of care and seeks to apply this experience to create similar for the AS patient through the program, Target: AS.

Hypothesis:
A key step in an Aortic Stenosis system of care is the identification of the patient’s diagnosis echocardiogram (echo). In some cases, the echo is initially performed at a location other than the tertiary hospital, and a consistent method of reporting the results to valve center does not currently exist. This inconsistency impacts guideline-based care.

Methods:
Target: AS pilot measures, following current guidelines, were developed with guidance from the AHA’s aortic stenosis scientific advisory group. Hospitals entered 2020 baseline data into the Target: AS data collection tool. Data elements were collected towards the measure: “Percentage of moderate aortic stenosis patients receiving a follow-up echocardiogram during the measurement period that is within 24 months of prior echocardiogram.” Sites reviewed data 24 months prior to the baseline year for the initial echo data.

Results:
123 patients in 8 pilot hospitals met inclusion criteria. Overall performance - 53% of patients had a follow-up echo with 24 months. Range was 0% - 65%. All but one patient that failed the measure was due to missing or unavailable prior echo. Engagement with sites through 1:1 interviews, data abstractor calls, and quarterly learning collaboratives revealed that hospitals are not able to find initial echo data in medical records, or that the information is not provided in a discrete manner.

Conclusions:
The 2020 ACC/AHA Guideline for the Management of Patients with Valvular Heart Disease states that patients diagnosed with moderate aortic stenosis should have a follow-up echo within 24 months of the diagnostic echo. Early data demonstrates that in all but one case, when hospitals cannot meet this guideline, it is due to not having the initial echo results. A hospital cannot monitor its adherence with guideline-based care when it does not have access to necessary data.
Abstract 11177: Uncontrolled Systolic Hypertension Exaggerates the Effect of Water Hammer Shock from a Retrograde Direction While Diastolic Hypertension Aggravates the Injury from an Antegrade Direction: New Mechanism of Coronary Artery Disease by Angiographic and Machine Learning Investigation
Authors: Nguyen Thach N , Truong Duc T , Le Thoa , Anh Le M , Nguyen Thu Q , Minh Le H , Tran Nghi , Le Chuong , Vu Loc , Pham Hung N , Ho Dung , Rigatelli Gianluca , Cao Thinh , Zuin Marco , Talarico Ernest , Nguyen Thuong Nghia T
Published: March 2022

Introduction:
Hypertension (HTN) is a strong risk factor of coronary artery disease.

Hypothesis:
Based on the damages induced by flow abnormalities in pipes, our research is built on the hypothesis that flow disturbances start the atherosclerotic process. Our strategy is to use today’s practice of fluid mechanics to unlock the mechanism of HTN on coronary plaques.

Methods:
All patients with uncontrolled HTN and unstable angina underwent coronary angiography and were selected if they had 1 or 2 moderate lesions. At first. contrast was injected until the index artery was completely opacified. As the injection stopped, the blood moved in and displaced the contrast. The movements and interactions of the blood flow in white color above a black background could be clearly analyzed. At the same time, Artificial Intelligence (Machine Learning (ML algorithms) program had 2 models built on Python. Model 1 was based on U-net and Densenet-121 for vessel segmentation. Model 2 was used for classification and movement of flow. Model 2 was trained based on the convolutional neural network. The main measurements were the types, durations and directions of flows.

Results:
20 patients were enrolled. 80% of lesions happened at the mid right coronary artery, near the bifurcation of the left anterior descending artery and diagonal, and of the circumflex artery and obtuse marginal. At the locations of lesions, 100% patients had turbulence caused by collision of the antegrade against the retrograde flow (water hammer shock). If there was excessive diastolic HTN >100mmHg, the duration of retrograde flow was short (<0.18 sec) and 75% turbulence happened DISTAL to the collision/bifurcation site. It happened due to higher gradient from proximal to distal. In severe systolic HTN, the duration of retrograde flow was longer (> 0.30 sec) and 80% turbulence happened PROXIMAL to the collision/bifurcation site due to higher gradient from distal to proximal.

Conclusions:
Uncontrolled diastolic HTN exaggerated the strength of antegrade flow and turbulence DISTAL to the collision/bifurcation site while uncontrolled systolic HTN intensified the retrograde flow and turbulence PROXIMAL to the collision/bifurcation site. Both inflicted damage on the intima and started the atheroslerotic process.
Abstract 11178: Non-Invasive Identification of Fibrotic Atrial Cardiomyopathy with Neural Networks Based on 642,400 12-Lead Ecgs from an Extensive Cohort Simulation Study
Authors: Nagel Claudia , Doessel Olaf , Loewe Axel
Published: March 2022

The clinical picture of fibrotic atrial cardiomyopathy is caused by a partial replacement of atrial myocardial tissue with fibrotic substrate. Being subject to electrical and structural remodeling processes, the substrate provides the necessary properties for the maintenance of atrial fibrillation and could thus be a good risk marker. We hypothesize that the P waves in the 12-lead ECG present a non-invasive and cost-effective tool to quantify the extent of atrial fibrosis as an alternative to state-of-the-art approaches. Our virtual patient cohort comprised a combination of 80 atrial, 25 thoracic geometries and 27 rotation angle variations of the atria. For each atrial model, 10 stages of fibrosis were defined by replacing different fractions of the myocardial volume with fibrotic tissue patches exhibiting remodeled ionic and conduction velocity properties. Conducting electrophysiological simulations in sinus rhythm on each model combination with one to three different healthy baseline conduction velocities yielded 642,400 synthetic ECGs. P wave duration, dispersion, peak-to-peak amplitudes and terminal force in V1 were calculated and served, together with atrial volumes and torso sizes, as an input for a regression neural network to estimate the volume fraction of atrial fibrosis. The root mean square error between the ground truth and the estimated extent of fibrosis was 8.74% left atrial fibrotic volume. Based on the regression results, a distinction between the healthy and the diseased cohorts was possible with an accuracy of 99.01%, a sensitivity of 99.57% and a specificity of 62.38%. In conclusion, we have gauged the potential of the 12-lead ECG for estimating fibrotic atrial volume fractions in an extensive cohort simulation study comprising both, functional and anatomical inter-subject variability. As a next step, the methods need to be validated with clinical data for which robust feature extraction algorithms are required.
Abstract 11183: A Classificatory Analysis of Right Heart Geometry and Dysfunction Provides Prognostic Stratification in Heart Failure of Any Left Ventricular Ejection
Authors: Casati Mattia , Bursi Francesca , Mondellini Giulio M , Santangelo Gloria , Santamaria Andrea , Rusconi Francesca , Valli Federica , Ferrante Giulia , TORTA DANIELA , Massironi Laura , Tarricone Diego , Stefano Carugo , Guazzi Marco
Published: March 2022

Introduction:
The prognostic role of the left heart dysfunction is established in heart failure (HF). However, focusing only on left ventricular ejection fraction (LVEF) may be reductive as HF with preserved ejection fraction (HFpEF) yields to poor outcomes, similarly to HF with reduced ejection fraction (HFrEF).

Hypothesis:
We investigated the prognostic role of the right ventricle (RV) phenotype through a classification based on RV end diastolic diameter (RVEDD) and tricuspid annulus systolic excursion (TAPSE) in chronic HF of any LVEF.

Methods:
We retrospectively examined two well-defined population of ambulatory patients with chronic HF: severe HFrEF (LVEF≦35%) and HFpEF (LVEF≧55%), all receiving optimal guideline-directed medical and device therapy, followed at a dedicated outpatient HF clinic. Patients were categorized by echocardiography based on RVEDD (cut-off 42 mm) and TAPSE (cut-off 17 mm) into four groups (above and below cut-offs): not dilated and not hypokinetic (NDNH), dilated and not hypokinetic (DNH), not dilated and hypokinetic (NDH) and dilated and hypokinetic (DH).

Results:
Among 256 patients (mean age 67±12 years, 75% men, 75% HFrEF, 60% ischemic), RVEDD and TAPSE were available for 202. Distribution of NDNH, NDH, DNH and DH is reported in the figure. Over a median follow-up of 4 years, 62 deaths occurred; KM-survival curves are shown in figure. After multivariable adjustment for age, HFpEF/HFrEF, and ischemic etiology, patients with DNH and DH showed increased risk of mortality (HR 2.4 95%CI 1.1-5.1 p=0.024; and 3.4 95%CI 1.7-6.7 p<0.001 respectively) compared to NDNH, with NDH showing comparable risk (HR 1.6 95%CI 0.9-3.7 p=0.232).

Conclusions:
In chronic HF receiving optimal medical and device therapy, a simple and easy to use RV classificatory analysis is worth of consideration out of LVEF categorization. RV dimensions rather than motility drive the mortality rate independently of age, HFpEF/HFrEF phenotype and HF etiology.
Abstract 11187: Perceptions of Patient Heart Failure Severity and Caregiver Inflammatory Markers: Interactions with Race and Education
Authors: Mayfield Megan E , Dunbar Sandra B , Higgins Melinda K , Bidwell Julie T , Gary Rebecca A
Published: March 2022

Background:
Heart failure (HF) caregivers (CGs) may experience stress due to unpredictable patient disease trajectory. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) are reported to be elevated in dementia CGs, but less is known about HF CGs response to stress or relationships with social determinants of health such as education and race.

Objective:
To determine if social factors (race, education) modify the relationship between patient disease severity trajectory (NYHA class) and CG stress as measured by inflammatory biomarkers of IL-6 and hs-CRP among HF CGs.

Methods:
A secondary analysis was conducted using baseline data from Caregiver Opportunities for Optimizing Lifestyle (COOL) trial. Education was dichotomized into technical/high school or less versus college or post-graduate degree. Race was dichotomized as African American (AA) or White/Asian due to the low number of Asian CGs. Two-way analysis of variance tests were conducted for IL-6 and hs-CRP to test interaction effects between CG perceived NYHA class and education or race.

Results:
Participants (n=127) were predominantly female (n=117, 92.1%), AA (n=74, 58.3 %), and the majority (70.1%) reported a college or post-graduate education. Perceived NYHA class were reported as: I (n=32, 25.6%), II (n=31, 24.8%), III (n= 47, 37.6%), and IV (n=15, 12.0%). For hs-CRP, there was a significant interaction between race and NYHA class (p=.013). Higher hs-CRP levels were noted in class II, compared to class I or class III for AA CGs (p=.004). White/Asian CGs did not have significant hs-CRP differences between NYHA classes (p=.634). While similar trends were observed for IL-6 between race and NYHA class, it did not reach statistical significance. In the model for education and perceived disease severity, NYHA class was significant (p=.038) for hs-CRP. In the post hoc test for NYHA class, hs-CRP was highest among NYHA class II (p<.02) for lower education levels. For IL-6, NYHA class was significant (p=.047); but the interaction effect with education was not significant (p=.687).

Conclusions:
Our findings suggest that CGs of AA race and/or lower education may experience higher stress earlier in the HF disease trajectory and may therefore benefit from targeted CG support interventions.
Abstract 11193: Incremental Diabetogenic Effect of Statin According to Its Intensity in Acute Myocardial Infarction Patients Following Successful Percutaneous Coronary Intervention
Authors: Choi Jah , Lee Jieun , Choi Byoung Geol , Park Soohyung , Lee Kyuho , Back Seungmin , Kang Dong , KIM Woohyeun , Roh Seung-young , Na Jin , Choi Cheol Ung , Kim Eung Ju , Park Chang Gyu , Seo Hong-Seog , Jeong Myung Ho , Rha Seung Woon
Published: March 2022

Introduction:
Although statin therapy is strongly recommended in acute myocardial infarction (AMI) patients, there has been consistent concern regarding the development of new onset diabetes mellitus (NODM). Currently, there has been no data whether diabetogenic effect of statin is intensity dependent. In this study, we investigated the impact of different statin intensity on incidence of NODM up to 3 years.

Methods:
Among 13,104 AMI patients enrolled in the Korea AMI Registry (KAMIR) between November 2011 and May 2015, we enrolled the 5,906 patients without diabetes mellitus and successful percutaneous coronary intervention (PCI). There were 22.8% (1,349/5,906) of patients received high intensity stain and 76.0% (4,488/5,906) patients received moderate intensity, and only 1.2% (69/5,906) patients received low intensity statin. The incidence of NODM were investigated among three different intensity of statins up to 3 years.

Results:
At baseline, high intensity statin group showed higher baseline LDL cholesterol level, body mass index, and abdominal circumference compared to other groups. In Kaplan-Meier curve, the cumulative incidence of NODM was significantly higher in high intensity group than mild and moderate intensity group (7.8% vs. 1.5% vs. 5.9% respectively, Log rank p-value = 0.002, Figure 1A). The incremental diabetogenic tendency was observed in each individual statin in dose-dependant manner (Figure 1B). In Cox regression, the intensity of statin was statistically significant prognostic factor of NODM after adjusting age, and other metabolic variables, such as body mass index, abdominal circumstance, and level of serum triglyceride.

Conclusions:
Among the AMI patients underwent successful PCI, higher intensity statin was associated with higher incidence of NODM, showing the diabetogenic effect of statin intensity.