bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 6923: Heart Weight, Fibrosis, and Coronary Artery Disease as Contemporary Substrates of Autopsy-Defined Sudden Arrhythmic Death: Insights from the POST SCD Study
Authors: Salazar James W , Connolly Andrew J , Feng Jean , Olgin Jeffrey E , Moffatt Ellen , Tseng Zian H
Published: April 2024

Introduction:
Studies of pathology underlying sudden cardiac death (SCD) are biased by low autopsy rates or a focus on ischemic pathology. Leveraging the POST SCD Study, a countywide postmortem study of all presumed (WHO-defined) SCDs, we hypothesized that autopsy would identify contemporary substrates of SCD independent of coronary artery disease (CAD).

Methods:
We compared postmortem findings for presumed SCDs (97% autopsy rate including toxicology and vitreous chemistries) adjudicated as autopsy-defined sudden arrhythmic death (SAD, potentially rescuable with implantable cardioverter-defibrillator [ICD]) or non-SAD, and trauma death (TD) controls in San Francisco, California from 2/1/2011-3/1/2014. Heart weight Z-scores were based on 27,645 reference autopsies.

Results:
We evaluated 525 presumed SCDs (293 SADs; 232 non-SADs) and 104 TDs. Mean SAD heart weight was 1.34 standard deviations above expected (Z-score 1.34,
Figure
), heavier (P<0.001) than non-SADs (Z-score 0.89) and TDs which closely matched expected weights (Z-score -0.02).Heart weight was heavier for SADs than non-SADs for cases without CAD (Z-score 1.4 vs. 0.7, P<0.001), but similar for cases with CAD. Chronic CAD was associated with higher risk of SAD (60% prevalence) than TD (14% prevalence; adjusted OR 7.0 [3.7-13.2], P<0.001); left anterior descending and right CAD conveyed highest risk. Adjusted for CAD, total fibrosis (replacement, interstitial) was higher for SADs (9.9 ± 8.0%) than non-SADs (7.5 ± 6%, P=0.018) and TDs (6.1 ± 5.8%, P=0.002). Compared to TDs, heart weight and total fibrosis were associated with SAD independent of CAD (P <0.05).

Conclusion:
In this 3-year study of autopsy-defined SAD, we identified chronic CAD, heart weight, and fibrosis as its pathologic substrates compared to prevalent cardiac pathology in the community. Since these factors can be assessed pre-mortem, they may be targets for contemporary risk stratification for SAD potentially rescuable with an ICD.
Abstract 6928: Trends and Mortality of Percutaneous and Open Cardiac Interventions in Diabetic Patients With Coronary Artery Disease: 18 Years National Perspective
Authors: Aroshidze Beka , Mirabal Susan C , Sircy Aaron , Visen Srishti S , Kahn Alexa B , Raina Jilmil , Shi Junxin , bakhtadze beka , Chkhikvadze Tamta
Published: April 2024

Introduction:
Coronary artery bypass grafting (CABG) is a preferred intervention in patients with diabetes and coronary artery disease (CAD). We aimed to analyze the trends and outcomes of interventions in diabetic patients with CAD and if there has been a shift in intervention types in this subset of patients.

Methods:
We queried Nationwide Inpatient Sample 2000-2018yy for adult patient discharged with associated ICD-9 and ICD-10 diagnosis and procedure codes for CAD and concomitant diabetes, who only underwent CABG or PCI and analyzed the procedure trend changes. Primary outcome was inpatient mortality.

Results:
A total of nationally estimated 42,887,309 adult hospitalizations were identified for diabetic patients with CAD from 2000-2018, with 3,653,882 PCI and 1,692,938 CABG procedures performed. Number of hospitalizations has gradually increased until 2011, and decreased afterwards. Although overall PCI numbers have dropped after 2015, likely related to ICD-9 to ICD-10 coding transition, the proportion of PCI procedures have followed the increasing trend of hospitalizations from 9.2% in 2000 to highest 11.3% in 2006 and 8% in 2018. Meanwhile the number of CABG has gradually decreased from 6.5% in 2000, reaching lowest <3% in 2011 and 4% in 2018. Inpatient mortality has decreased for patients who only received CABG from 2.35% (95% CI:2.09-2.62) in 2000 to 1.69% (95% CI: 1.46-1.93) in 2018, while increased for PCI from 1.29% (95%CI: 1.12-1.46 in 2000) to 2.65% (95%CI: 2.45-2.85 in 2018) (Figure 1).

Conclusion:
While hospitalizations have increased for diabetic patients with CAD, the inpatient mortality for CABG has decreased as well as proportion of CABG performed. Meanwhile, the proportion of PCI has increased, whereas mortality for PCI has doubled. Further analysis is necessary in selection of interventions in these patients and evaluating the risks and benefits of PCI compared to CABG.
Abstract 6940: Demographics and Healthcare Utilization of Percutaneous and Open Cardiac Interventions in Diabetic Patients With Coronary Artery Disease in the U.S
Authors: Aroshidze Beka , Visen Srishti , Mirabal Susan C , Shi Junxin , bakhtadze beka , Chkhikvadze Tamta
Published: April 2024

Introduction:
Socioeconomic, sex and racial disparities have been observed in percutaneous coronary interventions (PCI) and coronary artery bypass grafting (CABG). Our aim was to assess the nationwide trends and detect any changes in practice patterns.

Methods:
Nationwide Inpatient Sample (NIS) was analysed from 2000-2018 for adult hospitalizations with coronary artery disease (CAD) and diabetes who underwent PCI and CABG. Respective ICD-9 and ICD-10 diagnosis and procedural codes were used. Each intervention type group was analyzed separately for sociodemographic and resource utilization.

Results:
A total of 3,653,882 PCI and 1,692,938 CABG hospitalizations were analyzed. Both interventions have decreased in female patients and increased in minority groups. PCI rates increased evenly across the races, while CABG increased more in Hispanic, and Pacific Islander populations than Black and Native Americans. CABG has decreased in <59 as well as >70 age groups and increased in the 60-69 age group. Both PCI and CABG increased in publicly insured and significantly so in the lowest income population (PCI:7% in 2000 vs. 32% in 2018; CABG:7% to 30%, respectively) (Table 1.) All procedures have shifted to teaching hospitals between 2000-2018 (CABG: 63% to 83%; PCI: 63% to 73%). Mean hospitalization charges have increased by 28.7% for CABG (+Δ$49,613) and by 40% for PCI(+Δ$34,262); LOS increased for both PCI (+Δ16%; Mean LOS 3.4 to-3.9 days) and CABG (+Δ4.4%; Mean LOS 9.3 to 9.7 days). Overall, by 2018 inflation adjusted CABG hospitalisation cost was $222,634 and $119,316 for PCI.

Conclusion:
Our analysis has demonstrated the increasing trends of PCI, and CABG performance in minorities, publicly insured and patients residing in lowest socioeconomic areas. Efforts are necessary to address sex disparities and decreasing rate of interventions in females with diabetes and CAD.
Abstract 6988: The Role of Frailty in Identifying Benefit from Transcatheter versus Surgical Aortic Valve Replacement
Authors: Strom Jordan B , Xu Jiaman , Orkaby Ariela R , Shen Changyu , Charest Brian , Kim Dae H , Cohen David J , Kramer Daniel B , Spertus John , Gerszten Robert E , Yeh Robert W
Published: April 2024

Background:
Frailty is associated with a higher risk for adverse outcomes after aortic valve replacement (AVR) for severe aortic valve stenosis, but whether or not frail patients have differential benefit from transcatheter (TAVR) vs. surgical (SAVR) AVR is uncertain.

Methods:
We linked adults ≥ 65 years old in the US CoreValve High Risk (HiR) or Surgical or Transcatheter Aortic-Valve Replacement in Intermediate Risk Patients (SURTAVI) trial to 100% Medicare claims 2/2/2011-9/30/2015. Two frailty measures, a deficit-based (DFI) and phenotype-based (PFI) frailty index, based on the Rockwood and Fried definitions of frailty respectively, were generated for linked individuals. The absolute and relative treatment effect of TAVR vs. SAVR were evaluated within frailty index (FI) tertiles for the primary endpoint of death and non-death secondary outcomes, as defined by the trials, using multivariable Cox regression. Functional status decline was additionally in TAVR vs. SAVR by FI tertile using multivariable logistic regression.

Results:
Of 1,442 (linkage rate = 60.0%) individuals in the linked HiR and SURTAVI trials, 741 (51.4%) individuals received TAVR and 701 (48.6%) received SAVR (mean age 81.8 ± 6.1 years, 44.0% female, mean Society of Thoracic Surgeons risk score 5.9 ± 2.7). Those in higher FI tertiles had a greater burden of comorbidities. Though the rates of death in the highest FI tertiles (DFI 38.6%, PFI 33.8%) were 2-3-fold higher than the lowest tertile (DFI 14.8%, HR 2.86, 95% CI 2.15-3.79, p < 0.001; PFI 17.9%; HR 2.05, 95% CI 1.58-2.67, p < 0.001), there were no significant differences in the relative or absolute treatment effect of SAVR vs. TAVR across FI tertiles for all death, non-death, and functional outcomes (all interaction p-values > 0.05). Results were overall consistent across individual trials and frailty definitions (
Figure
).

Conclusions:
Among CoreValve trial participants linked to Medicare claims, two different frailty indices based on Fried and Rockwood definitions identified individuals at higher risk of death and functional decline but no differential benefit from TAVR vs. SAVR.
Abstract 8859: Hematopoietic
Calr
Frameshift Mutation Exacerbates Hypoxia-Induced Pulmonary Hypertension in Mice
Authors: Yokokawa Tetsuro , Misaka Tomofumi , Kimishima Yusuke , Minakawa Keiji , Sugimoto Koichi , Nakazato Kazuhiko , Ikeda Kazuhiko , Takeishi Yasuchika
Published: April 2024

Introduction:
Calreticulin (
CALR
) frameshift is the second frequent driving mutation in myeloproliferative neoplasms (MPNs). MPNs are complicated with pulmonary hypertension (PH), but the mechanistic relevance of the
CALR
mutations on PH has not yet been clarified.

Methods and Results:
We generated a 10-bp deletion knock-in mice with murine
Calr
exon 9 mimicking the human
CALR
mutations. To investigate whether the hematopoietic CALR mutation contributes to PH, a bone marrow transplantation (BMT) was applied using the donor BM cells from
Calr
knock-in mice or control wild-type (WT) mice. Four weeks after BMT, the recipient mice transplanted with BM cells from
Calr
knock-in mice (Del-R) and WT mice (WT-R) were exposed to chronic hypoxia. Three weeks after starting chronic hypoxia exposure, the right ventricular systolic pressure and right ventricle/left ventricle-plus-septum weight ratio in the Del-R mice were significantly increased compared to the WT-R mice. Lung histology showed an acceleration of pulmonary arterial muscularization and medial wall thickness in Del-R mice after chronic hypoxia. Increases in macrophage infiltration was similarly observed in both WT-R and Del-R mice after chronic hypoxia. Endothelin-1 expression and STAT3 phosphorylation were significantly upregulated in the lung of Del-R mice compared to the WT-R mice in response to chronic hypoxia. Using
Calr
Del/CAG-EGFP double transgenic mice, we visualized the accumulations of donor-derived macrophages in pulmonary arterial regions. BM-derived macrophages carrying the
Calr
mutation showed increases in endothelin-1 expression, indicating that BM-derived macrophages with the
Calr
mutation played important roles in the pulmonary arterial remodeling.

Conclusion:
The frameshifted
Calr
mutations presented a novel mechanism of PH through BM-derived macrophages accompanied by upregulation of endothelin-1.
Abstract 8864: Left Bundle Branch Area Pacing is Non-Inferior to His Bundle Pacing in Achieving Physiologic Repolarization and T-Wave Memory Resolution
Authors: Gupta Anshul , Pavri Behzad B
Published: April 2024

Introduction:
We have previously reported that His bundle pacing (HBP) results in more physiologic ventricular repolarization as compared to conventional biventricular pacing. Left bundle branch area pacing (LBAP) is increasingly used as the preferred modality of physiologic pacing due to ease of implantation and low long-term pacing thresholds. LBAP and HBP are comparable in terms of achieving physiologic left ventricular (LV) depolarization. However, their effects on ventricular repolarization have not been assessed. Established ECG markers of arrhythmic risk can be used to compare ventricular repolarization across these two modalities of physiologic pacing.

Hypothesis:
LBAP is not inferior to HBP in its effects on ventricular repolarization and T-wave memory resolution.

Methods:
The following parameters were analyzed in patients with HBP (n = 34) and LBAP (n = 16) from post-implant ECGs:

1) QTc: QT corrected using Bazett’s formula in lead V5, and if not measurable, in V4 or V6

2) QTc Dispersion: Longest minus shortest QTc from precordial leads

3) Tp-Te Transmural: T-peak minus T-end in same lead as 1)

4) Tp-Te Total: Earliest T-peak minus latest T-end from all precordial leads

5) Tp Dispersion: Latest minus earliest T-peak from precordial leads

To analyze T-wave memory resolution, QRS-T angles were compared using ECGs within 10 days of and after ≥ 25 days post implant.

Results:
See tables. Median time from implant to 1st ECG for both groups was ≤1 day. None of the repolarization parameters were significantly different in HBP vs. LBAP groups.

Conclusion:
All repolarization markers of arrhythmic risk were similar in HBP vs. LBAP. Both modalities showed similar effects on T-wave memory resolution. These data suggest that LBAP, in addition to achieving physiologic LV depolarization, is not inferior to HBP in achieving physiologic ventricular repolarization. These observations further support the increasing use of LBAP as the preferred modality for physiologic pacing.
Abstract 8895: Design of Phase IV, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Trial Evaluating Sodium Zirconium Cyclosilicate for the Management of Hyperkalemia in Patients With Symptomatic Heart Failure With Reduced Ejection Fraction (REALIZE-K Trial)
Authors: Kosiborod Mikhail , Cherney David , Desai Akshay S , Petrie Mark , Testani Jeffrey , Verma Subodh , Al-Shurbaji Ayman , Eudicone James M , Zarzuela Donna
Published: April 2024

Introduction:
International guideline-recommended therapies for heart failure (HF) with reduced ejection fraction (HFrEF), including mineralocorticoid receptor antagonists (MRA), are underutilized, in part due to concerns of hyperkalemia (HK) especially among those at high risk. The REALIZE-K trial aims to evaluate the efficacy and safety of sodium zirconium cyclosilicate (SZC), a selective potassium (K
+
) binder, to enable MRA use in patients with HFrEF at high risk for HK.

Methods:
REALIZE-K is a prospective, double-blind, placebo (PBO)-controlled randomized withdrawal trial enrolling symptomatic HFrEF (NYHA class II-IV and LVEF ≤40%) patients on guideline-directed medical therapy (but not full-dose MRA) with either HK (serum K
+
5.1-5.9 mmol/L) or high risk for HK during MRA titration. All eligible patients enter a 1-month open-label run-in phase, during which patients with hyperkalemia receive SZC to correct HK; all patients undergo protocol-mandated titration of spironolactone (SPL) as tolerated to a target of 50 mg QD with supplemental SZC to maintain normokalemia (serum K
+
3.5-5.0 mmol/L;
Figure
). All patients tolerating ≥25 mg QD of SPL will be randomly assigned to continued SPL+SZC or SPL+PBO during an 8-month double-blind withdrawal phase. Serial K
+
monitoring will guide protocol-directed dosing of SZC/PBO and SPL during the randomized period. The primary study endpoint is the occurrence at 8 months of normokalemia on SPL ≥25 mg QD without the need for rescue therapy for severe HK in the SZC vs PBO group. Secondary endpoints include individual components of the primary endpoint and health status assessed by Kansas City Cardiomyopathy Questionnaire Total Symptom Score. Exploratory endpoints include time to first occurrence of the composite of CV death or worsening HF, and change in mean urine albumin-creatinine ratio.

Conclusions:
REALIZE-K will evaluate the efficacy and safety of SZC, enabling MRA therapy for HFrEF patients at high risk for HK.
Abstract 9018: Risk of Ventricular Arrhythmias Following Implantable Cardioverter-Defibrillator Generator Change in Patients With Recovered Ejection Fraction: Implications for Decision-Making
Authors: Chang Donald D , Pantlin Peter , Benn Francis , Williams Cody M , Bernard Michael L , Hiltbold Aimee E , Khatib Sammy , Polin Glenn M , Rogers Paul A , Morin Daniel P
Published: April 2024

Introduction:
Guidelines indicate primary-prevention ICDs for most patients with LVEF ≤35%. Some patients’ EFs improve to >35% during the life of their first ICD. In present practice, ICDs most often are replaced regardless of EF. In patients with recovered EF>35% who have never received appropriate ICD therapy, the utility of ICD generator replacement remains unclear. We evaluated the risk of ventricular arrhythmias in relation to EF at the time of ICD generator change in patients with no history of appropriate tachycardia therapy from their original ICD.

Methods:
We enrolled patients with a primary-prevention ICD originally implanted for systolic cardiomyopathy with EF ≤35%, who underwent ICD generator change within our multihospital health system. Patients who required appropriate ICD therapy for VT/VF prior to generator change were excluded.

Results:
Among 539 generator changes, 291 patients (69±12 y, 63% men, 29% Black, EF 34±15%) met inclusion criteria. During follow-up of 3.9±2.3 years, 62 (21%) received appropriate therapy for VT/VF. Compared to patients with recovered EF >35% (n=109 [37%]), those with EF persistently ≤35% (n=182 [63%]) were more likely to require subsequent ICD therapy (12% vs. 27%, p=0.003). ROC analysis among those with EF >35% revealed the optimal cutoff for VT/VF prediction to be EF 45% (AUC 0.71, p=0.01). Kaplan-Meier analysis demonstrated considerably higher VT/VF-free survival among those with LVEF ≥45% vs. <45% (Figure; p<0.001); estimated 5-year event rates: 6% vs. 35%. On multivariable analysis, EF was independently predictive of VT/VF (adjusted HR per 1% EF increase: 0.90 [0.81-0.99]; p=0.04).

Conclusion:
At the time of ICD generator change, patients with primary-prevention ICDs and EF ≥45% with no prior ICD therapy have a significantly lower rate of subsequent ventricular arrhythmias compared to those with EF <45%. These data may be useful during shared decision-making at the time of ICD generator battery depletion.
Abstract 9030: Effects of Edoxaban on Clinical Outcomes in Extremely Elderly Patients (aged ≥ 90 Years) With Atrial Fibrillation: A Subanalysis of Data from the ELDERCARE-AF Trial
Authors: Kuroda Masaru , Tamiya Eiji , Nose Takahisa , Ogimoto Akiyoshi , Taura Junki , Imamura Yuki , Fukuzawa Masayuki , Hayashi Takuya , Akao Masaharu , Yamashita Takeshi , Lip Gregory , Okumura Ken
Published: April 2024

Introduction:
Atrial fibrillation (AF) affects about 10% of the very elderly (≥ 80 years), and its prevalence increases exponentially with age. Data are lacking on the efficacy and safety of anticoagulants in extremely elderly AF patients (≥ 90 years). We tested the hypotheses that such patients are at increased risk of stroke or systemic embolism (SSE) and could benefit from low-dose edoxaban.

Methods:
This was a subanalysis of ELDERCARE-AF, a multicenter, double-blind, phase 3 study in which very elderly Japanese patients with non-valvular AF (NVAF) considered ineligible for standard anticoagulants were randomly allocated to low-dose edoxaban (15 mg once daily) or placebo. Outcomes were compared between the three prespecified subgroups of age at baseline 80-84, 85-89, and ≥ 90 years. Primary efficacy and safety endpoints were incidence of SSE and ISTH-defined major bleeding, respectively (% per patient-year).

Results:
A total of 984 patients were randomized. Mean (± SD) age and CHADS
2
score of the patients aged ≥ 90 years were 92.3 (2.1) years and 3.1 (1.1), respectively. SSE occurred in 14/354 (2.8%), 25/374 (5.0%), and 20/256 (6.1%) of patients aged 80-84, 85-89, and ≥ 90 years, respectively; its incidence was significantly higher in the ≥ 90 years vs 80-84 years group (HR = 2.16 [95% CI, 1.09-4.27],
P
= 0.03). Major bleeding occurred in 6/353 (1.3%), 12/373 (2.6%), and 13/256 (4.3%) of patients aged 80-84, 85-89, and ≥ 90 years, respectively; its incidence was significantly higher in the ≥ 90 years vs 80-84 years (HR = 3.42 [1.30-9.01],
P
= 0.01). In this patient group ≥ 90 years with higher SSE and major bleeding incidences, edoxaban showed a significantly lower SSE incidence than placebo (4/129 [2.4%] vs 16/127 [10.1%]; HR = 0.23 [0.08-0.68],
P
= 0.008); however, edoxaban showed a greater tendency toward major bleeding than placebo (10/129 [6.5%] vs 3/127 [2.1%]; HR = 3.02 [0.82-11.21],
P
= 0.10), and significantly higher incidence of gastrointestinal bleeding (9/129 [5.9%] vs 1/127 [0.7%]; HR = 8.37 [1.04-67.07],
P <
0.05).

Conclusions:
In extremely elderly Japanese NVAF patients, low-dose edoxaban may be an option for preventing SSE. The prophylactic benefit must be balanced against the increased risk of major bleeding, particularly gastrointestinal bleeding.
Abstract 9031: Blood-Based Epigenetic Markers of FKBP5 Gene Methylation in Patients With Dilated Cardiomyopathy
Authors: WADA KENTO , Misaka Tomofumi , Yokokawa Tetsuro , Kimishima Yusuke , Kaneshiro Takashi , Oikawa Masayoshi , Yoshihisa Akiomi , Takeishi Yasuchika
Published: April 2024

Background:
Blood-based DNA methylation patterns are linked to types of diseases. FKBP5, a protein cochaperone, is known to be associated with the inflammatory response, but the regulatory mechanisms by leukocyte
FKBP5
DNA methylation in DCM patients remain unclear.

Methods and Results:
The present study enrolled DCM patients (n = 31) and age- and sex-matched control subjects (n = 43). We assessed
FKBP5
CpG methylation of CpG islands at the 5’ side as well as putative promoter regions by methylation-specific quantitative polymerase chain reaction using leukocyte DNA isolated from the peripheral blood.
FKBP5
CpG methylation levels at the CpG island of the gene body and the promoter regions were significantly decreased in DCM patients. Leukocyte
FKBP5
and
IL-1β
mRNA expression levels were significantly higher in DCM patients than in controls. The protein expressions of DNMT1 and DNMT3A in leukocytes were significantly reduced in DCM patients.
In vitro
methylation assay revealed that
FKBP5
promoter activity was inhibited at the methylated conditions in response to immune stimulation, suggesting the decreased
FKBP5
CpG methylation was functionally associated with elevation of
FKBP5
mRNA expressions. Histological analysis using a mouse model with pressure overload showed that FKBP5-expressing cells were substantially infiltrated in the myocardial interstitium in the failing hearts, indicating a possible role of FKBP5 expressions of immune cells in the cardiac remodeling.

Conclusions:
Our findings demonstrate a link between specific CpG hypomethylation of leukocyte
FKBP5
and DCM. Blood-based epigenetic modification in
FKBP5
may be a novel molecular mechanism that contributes to the pathogenesis of DCM.
Abstract 9060: Do Women Fare Differently After Repair of Acute Type a Aortic Dissection?
Authors: Pupovac Stevan S , Hemli Jonathan M , Catalano Michael , Scheinerman S J , Hartman Alan R , Brinster Derek R , Yu Pey-Jen
Published: April 2024

Introduction:
Given that the data regarding sex-based differences in presentation, management and outcomes following repair of acute type A aortic dissection (ATAAD) is sparse and inconsistent, we sought to examine the contemporary practice pattern and outcomes of ATAAD repair in females, as compared with men.

Hypothesis:
We hypothesize that female patients undergoing surgical repair of acute type A aortic dissection will have 30-day morbidity and mortality rates comparable to their matched control male peers, although this may be impacted by age; sex, body mass index, advanced age, hemodynamic instability at clinical presentation, and presence of a preoperative malperfusion syndrome, are all independent risk factors for poorer short-term outcomes..

Methods:
Out of 240 cases of ATAAD between June 2014 and December 2019, 231 patients were divided into 2 groups based on sex. From this, 47 pairs of propensity-matched patients were analyzed with respect to operative data and short-term clinical outcomes.

Results:
Overall 30-day mortality for our entire study cohort was 11.8% (27 deaths), significantly greater in females (21.4%, 15 deaths
vs.
7.5%, 12 deaths,
P
= 0.002); this difference was not observed in the matched cohort (19.1%, 9 deaths
vs.
8.5%, 4 deaths,
P =
0.14). Women more commonly undergo isolated replacement of the ascending aorta (78.7%
vs.
59.6%,
P
< 0.001), whereas aortic root replacement is performed more frequently males (53.2%
vs.
19.1%,
P
< 0.001). There is no significant difference in the incidence of major postoperative morbidity between sexes. Advanced age is associated with great 30-day mortality after ATAAD repair (OR 1.93).

Conclusions:
The significant difference in 30-day mortality observed in the overall cohort, was not observed in the matched cohort. This may suggest that the overall difference in outcomes with regards to sex, is secondary to the differences seen in age and presentation and not inherent to sex itself.
Abstract 9074: Cardiovascular Phenotypes Profiling for Congenitally Corrected Transposition of the Great Arteries and Its Prognosis Implication
Authors: He Qiyu , Shen Huayan , Zhou Zhou , Li Shoujun
Published: April 2024

Introduction:
Congenitally corrected transposition of the great arteries (ccTGA) is a rare and complex congenital heart disease with the characteristics of double discordance. Enormous accompanied anomalies are the culprit of difficult prognosis evaluation and clinical decisions.

Hypothesis:
To delineate a novel ccTGA clustering modality under HPO instruction and elucidate the relationship between phenotypes and prognosis in ccTGA patients.

Methods:
A retrospective review of 270 patients diagnosed with ccTGA in Fuwai hospital from 2009 to 2020 and cross-sectional follow-up was performed. Human Phenotype Ontology (HPO)-instructed clustering method was administered in ccTGA classification. Kaplan-Meier survival, Landmark analysis, and cox regression analysis were used to investigate the difference of outcomes between clusters with the combination of surgeries.

Results:
The median follow-up time was 4.29 (2.07-7.37) years. A total of three distinct phenotypic clusters were obtained after HPO-instructed classification with 21 in cluster 1, 136 in cluster 2, and 113 in cluster 3. Landmark analysis revealed significantly worse mid-term outcomes in all-cause mortality (p=0.042) and composite endpoints (p=0.008) of cluster 3 in comparison with cluster 1 and cluster 2. Multivariate analysis indicated that pulmonary arterial hypertension (PAH), atrioventricular septal defect (AVSD), and arrhythmia were risk factors for composite endpoints. Moreover, the surgical treatment was significantly different among the three groups (p<0.001) and surgical strategies had different effects on the prognosis of the different phenotypic clusters.

Conclusions:
HPO-instructed clustering method delineates a novel image of ccTGA classification that might improve prognosis prediction and clinical decision.
Abstract 9077: Long-Term Prognostic Value of Controlling Nutritional Status Score and Six-Minute Walk Distance in Patients With Implantable Cardioverter Defibrillator
Authors: Kawasaki Masato , Yamada Takahisa , Watanabe Tetsuya , Morita Takashi , Kikuchi Atsushi , Kawai Tsutomu , Seo Masahiro , Nakamura Jun , Kayama Kiyomi , Ueda Kunpei , Sakamoto Daisuke , Kougame Takehiro , Tamura Yuto , Fujita Takeshi , Nishigaki Keisuke , Kokubu Yuki , Fukuda Yuto , Fukunami Masatake
Published: April 2024

Backgrounds:
Both Controlling Nutritional Status (CONUT) score and 6-minute walk distance (6MWD) provide prognostic information in patients with chronic heart failure. However, there is little information available on long-term prognostic value of CONUT score and 6MWD for the prediction of severe ventricular tachyarrhythmias and cardiac death in implantable cardioverter defibrillator (ICD) patients.

Methods and Results:
We prospectively enrolled 233 consecutive outpatients with ICD (age: 66±14 years, male: 82%, NYHA class: 1.7±0.7, LVEF: 47±17%). At entry, laboratory data and 6MWD were obtained in all patients. During a follow-up period of 4.3±2.8 years, 75 patients had appropriate ICD discharge for severe ventricular tachyarrhythmias and 45 patients had cardiac death. At multivariate Cox regression analysis, 6MWD was significantly and independently associated with appropriate ICD discharge after adjustment with age, sex, NYHA class and LVEF, while CONUT score was not. Patients with short 6MWD (≤300m) had a higher risk of appropriate ICD discharge (42 % vs 23%, p=0.0002). On the other hand, at multivariate Cox regression analysis, CONUT score was significantly and independently associated with cardiac death after adjustment with age, sex, NYHA class and LVEF, while 6MWD showed the association with cardiac death at univariate analysis. Patients with higher CONUT score (≥4) had a higher risk of cardiac death (35% vs 15%, p<0.0001).

Conclusions:
CONUT score would be associated with cardiac death, while 6MWD might be associated with appropriate ICD discharge, in patients with ICD.
Abstract 9079: Omentin Reduces Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Apolipoprotein E Knockout Mice
Authors: FANG LIXIN , Ohashi Koji , Takikawa Tomonobu , Ozaki Yuta , Takahara Kunihiro , Murohara Toyoaki , Ouchi Noriyuki
Published: April 2024

Background:
Abdominal aortic aneurysm (AAA) is a life-threatening disease worldwide. Obesity is associated with an increased risk of AAA. Omentin is an adipokine, which is downregulated by obesity. Here we investigated the effect of omentin on angiotensin (Ang) II-induced AAA formation in apolipoprotein-E knockout (apoE-KO) mice.

Methods and Results:
ApoE-KO mice were crossed with transgenic mice expressing the human omentin in fat tissue (OMT-Tg mice). ApoE-KO/OMT-Tg and apoE-KO mice were subjected to continuous Ang II infusion. ApoE-KO/OMT-Tg mice exhibited a reduced maximal diameter of AAA compared with apo-E KO mice evaluated by macroscopic and ultrasound analyses. ApoE-KO/OMT-Tg mice showed a reduction of elastic fiber degradation in aorta compared with apoE-KO mice. ApoE-KO/OMT-Tg mice also displayed reduced expression levels of matrix metalloproteinase (MMP) 9, MMP2, pro-inflammatory mediators and macrophage surface marker, F4/80, in aortic walls compared with apo-E-KO mice. Conversely, intravenous administration of adenoviral vectors expressing omentin (Ad-OMT) significantly reduced maximal diameter and elastic fiber degradation of abdominal aorta after Ang II infusion in apoE-KO mice compared with control Ad-β-gal treatment. Treatment of human monocyte-derived macrophages with omentin protein attenuated activity and expression of MMP9 and NF-κB phosphorylation after stimulation with lipopolysaccharide. Treatment of human aortic smooth muscle cells with omentin protein attenuated activity and expression of MMP2 after stimulation with tumor necrosis factor α. The suppressive effects of omentin on MMP9 and MMP2 expression in macrophages and vascular smooth muscle cells were reversed by inhibition of PI3-kinase/Akt signaling or blockade of integrin αVβ3. Finally, continuous administration of PI3-kinase inhibitor LY294002 reversed the suppressive effects of Ad-OMT on maximal diameter and elastic fiber degradation of abdominal aorta in apoE-KO mice after Ang II infusion.

Conclusion:
Our data indicate that omentin acts as an adipokine that can attenuate Ang II-induced development of AAA by reducing MMP9 and MMP2 expression through the integrin αVβ3/PI3-kinase/Akt signaling in the vascular wall.
Abstract 9100: Two-Dimensional Speckle Tracking Echocardiography in Assessing the Subclinical Myocardial Dysfunction in Patients With Gestational Diabetes Mellitus
Authors: Li Wei , Li Ziyao , Liu Wei , Zhao Peng , Wang Zhenzhen
Published: April 2024

Introduction and Hypothesis:
Gestational diabetes mellitus (GDM) refers to impaired glucose tolerance first diagnosed during pregnancy, which may increase the risk of incident cardiovascular disease. Asymptomatic subclinical myocardial dysfunction already exists before the GDM diagnosis. In this study, we hypothesize that the two-dimensional speckle tracking echocardiography (2D-STE) may identify the subclinical impairment of GDM on the maternal left ventricular function.

Methods:
We prospectively enrolled 47 women with GDM and 62 healthy pregnant women (control group) at their 24~28 weeks of gestation who underwent transthoracic echocardiography (TTE). GDM diagnosis was in agreement with the IADPSG criteria. TTE was performed according to the recommendations of the American Society of Echocardiography. Conventional and 2D-STE parameters were compared between the two groups.

Results:
Age, gestational weeks, heart rate, and conventional echocardiographic parameters had no difference between the two groups. LV global longitudinal strain (LV-GLS) was lower in GDM (18.14 ± 2.53 vs. 22.36 ± 6.33, p< 0.001). LA reservoir and conduit phasic strain also decreased in patients with GDM (32.71 ± 6.64 vs. 38.00 ± 7.06, 20.41 ± 5.69 vs. 25.56 ± 5.73, p< 0.001). However, there was no significant difference regarding LA contractile function between the two groups. In multivariate regression analysis, the LV-GLS and LA conduit strain independently associated with GDM. Furthermore, the LA conduit strain may be a predominant parameter to illustrate subclinical myocardial deterioration in patients with GDM.

Conclusions:
Two-dimensional speckle tracking echocardiography may sensitively provide quantitative parameters, such as LV-GLS and LA conduit strain, to illuminate subclinical myocardial dysfunction in patients with GDM.
Abstract 9104: Pulmonary Endothelial Nedd9 and the Prothrombotic Pathophenotype of Acute Respiratory Distress Syndrome Due to Sars-cov-2 Infection
Authors: Alba George A , Samokhin Andriy , Hariri Lida P , Shih Angela , Haley Kathleen J , Padera Robert F , Vargas Sara O , Thompson Taylor , Mitchell Richard N , Maron Bradley A
Published: April 2024

Background:
The pathobiology of
in situ
pulmonary thrombosis in acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is incompletely characterized. In human pulmonary artery endothelial cells (HPAECs), hypoxia upregulates expression of a pro-thrombotic NEDD9 peptide (N9
p
) on the extracellular plasma membrane surface. We hypothesized that increased pulmonary endothelial N9
p
is a novel feature of the SARS-CoV-2 pathophenotype.

Methods:
Paraffin-embedded autopsy lung specimens were acquired from patients with ARDS due to SARS-CoV-2 infection (n=13), ARDS of other causes (n=10), and non-disease controls (n=5). Immunofluorescence characterized expression of N9
P
, fibrin, and TCF12, a putative binding target of SARS-CoV-2 and known transcriptional regulator of
NEDD9
. We performed RNA-Seq on mRNA isolated from control HPAECs treated with normoxia or hypoxia (0.2% O
2
) for 24 hr. Immunoprecipitation-liquid chromatography-mass spectrometry (IP-LC-MS) profiled protein-protein interactions involving N9
p
relevant to thrombus stabilization.

Results:
Compared to non-SARS-CoV-2-ARDS lungs, pulmonary endothelial N9
P
expression and N9
P
-fibrin colocalization was increased by 174% (P<0.002) and 212% (P<0.001) in SARS-CoV-2-ARDS, respectively. Compared to normoxia, hypoxia increased TCF12 mRNA quantity significantly in HPAECs
in vitro
[+1.19-fold, P=0.001; false discovery rate (FDR)=0.005]. Pulmonary endothelial nuclear TCF12 expression was also increased by 370% in SARS-CoV-2-ARDS vs. controls. In HPAEC plasma membranes, IP-LC-MS identified a novel protein-protein interaction between NEDD9 and the β3 subunit of the αvβ3 integrin, which regulates fibrin anchoring to endothelial cells.

Conclusions:
Compared to non-SARS-CoV-2-ARDS, SARS-CoV-2-ARDS is associated with increased pulmonary endothelial N9
p
expression and N9
p
-fibrin colocalization in microthrombi
in situ
. Increased hypoxia signaling or SARS-CoV-2-mediated regulation of TCF12 are potential mechanisms by which to explain these findings. Identifying N9
p
in the pulmonary microthrombi of SARS-CoV-2 lungs may have important pathobiological and, potentially, therapeutic implications for ARDS patients.
Abstract 9110: Use of a Genetic Risk Score to Predict Atrial Fibrillation in Patients With Cardiovascular Disease
Authors: Garfinkel Amanda C , Marston Nicholas A , Kamanu Frederick K , Melloni Giorgio M , Roselli Carolina , Bhatt Deepak L , Bonaca Marc P , Cannon Christopher P , Giugliano Robert P , Odonoghue Michelle L , RAZ Itamar , Scirica Benjamin M , Braunwald Eugene , Ellinor Patrick T , Lubitz Steven A , Sabatine Marc S , Ruff Christian T
Published: April 2024

Background:
Early detection of atrial fibrillation (AF) could permit earlier anticoagulation and thus potentially reduce risk of embolic stroke. A validated genetic risk score (GRS) has been shown to predict AF risk but its clinical utility beyond established AF risk factors is unclear.

Methods:
We performed a prospective cohort analysis in pts w/o prior AF from 4 TIMI trials [SOLID-TIMI 52, SAVOR-TIMI 53, PEGASUS-TIMI 54, FOURIER (TIMI 59)]. Pts were divided into genetic risk quintiles using a validated 1,018 SNP GRS for AF. Clinical risk for AF was also calculated using the validated CHARGE-AF model (age, ht, wt, SBP, DBP, anti-HTN med, DM, CHF, MI, smoking). 3-year KM rates and adjusted HRs were calculated across clinical and genetic risk groups. C-index was used to determine if the addition of GRS improved AF prediction compared with clinical risk and NT-proBNP.

Results:
In 36,663 pts followed for a median of 2.3 yrs, 1,018 new AF cases (2.8%) were identified. AF GRS predicted a significant risk gradient for AF with a 33% increased risk per 1-SD increase in GRS (HR 1.33 [95%CI 1.26-1.41]; p<0.001). Those in the top quintile of AF GRS were more than 2-fold more likely to develop AF (HR 2.26 [1.84-2.78], p<0.001) compared with the bottom quintile. This risk prediction was on par with age and stronger than any other clinical risk factor. Further, GRS provided an additional gradient of risk stratification on top of the CHARGE-AF clinical risk score, such that pts with high GRS and CHARGE-AF score had an 8.1% 3-year AF risk
(Fig)
. The C-index for CHARGE-AF was 0.64 (0.63-0.66); addition of NT-proBNP raised the C-index to 0.67 (0.65-0.69), and inclusion of GRS increased it further to 0.69 (0.67-0.71) (p<0.001).

Conclusion:
In pts with CV disease, AF GRS is a strong independent predictor of incident AF that provides complementary predictive value when added to a validated clinical risk score. AF GRS may be a clinically useful tool to identify very high-risk pts for consideration of AF screening.
Abstract 9122: Polyvalvular Heart Disease in Children Associated With FilaminA Mutations
Authors: Deng Ellen S , Araten Sarah B , Yamada Jessica M , Walsh Michelle L , Lai Abbe , Choudhury Sangita , Chen Ming
Published: April 2024

Introduction:
FilaminA (
FLNA
), an X-linked gene encoding an actin binding protein, is one of the only known causative genes for periventricular nodular heterotopia (PVNH) and mitral valve (MV) prolapse.
FLNA
mutations have been well associated with familial MV prolapse and polyvalvular disease in adults. There is limited data, however, on the type and distribution of valve disease in children with
FLNA
mutations. We aim to assess the frequency of polyvalvular disease in a predominantly pediatric cohort.

Methods:
We retrospectively enrolled subjects from a large registry at Boston Children’s Hospital of patients and families with PVNH and
FLNA
mutations with at least one transthoracic echo and clinical phenotyping of their cardiovascular and neurologic status. Additionally, data from published subjects with
FLNA
mutations and PVNH were included in the cohort. Imaging data about valvular heart disease were extracted for all subjects.

Results:
165 patients with
FLNA
mutations formed our cohort (128 F, median age 9 yrs, range 0-71 yrs), with 53% ≤ 21 yrs. Valve disease was the most common type of isolated structural disease, presenting in 58% (62/110) of
FLNA
patients with congenital heart disease. Of these patients, 45% (28/62, 10 M) had polyvalvular disease and 36% (22/62, 8 M) underwent cardiac surgery. MV prolapse or dysplasia was present in 60% (37/62) of patients. Aortic valve abnormalities were equally common, also occurring in 60% (37/62) of patients (e.g. bicuspid aortic valves and aortic valve prolapse). Notably, tricuspid valve dysplasia did not occur independently (n=0), and always presented with involvement of other cardiac valves. In patients with polyvalvular disease, mitral and aortic valves were most commonly involved together, occurring in 23% (14/62) of patients. Males with
FLNA
mutations were more likely to have polyvalvular disease with more severe clinical phenotypes.

Conclusions:
In this largest cohort of predominantly children with
FLNA
mutations,
FLNA
patients frequently have polyvalvular disease on echocardiography. When polyvalvular disease is detected especially involving the tricuspid valve, pediatric cardiologists should consider genetic testing for
FLNA
mutations as a potential contributor of disease.
Abstract 9153: Predictive and Protective Factors of Early, Late, and Very Late Stent Thrombosis in Acute Coronary Syndrome Patients Undergoing Coronary Stent Implantation: Findings from the Atlas Acs 2-timi 51 Trial
Authors: Chi Gerald , Alkhalfan Fahad , Lee Jane J , Memar Montazerin Sahar , Fitzgerald Clara , Korjian Serge , Omar Wally , Barnathan Elliot , Plotnikov Alexei , Braunwald Eugene , Gibson C. Michael
Published: April 2024

Introduction:
Stent thrombosis (ST) is an uncommon but serious complication of stent implantation. The aim of this analysis was to explore predictive and protective factors of early, late, and very late ST.

Methods:
This was a post-hoc analysis of the ATLAS ACS 2-TIMI 51 trial, which included acute coronary syndrome patients who received stent placement. Incidence of ST was assessed by Kaplan-Meier estimates at 30 days, 31 to 360 days, 361 to 720 days, and up to 720 days, with day 1 defined as the day of stent implantation. Multivariable associations with ST were explored by fitting Cox proportional hazards models. The covariates included patient characteristics, baseline laboratory tests (i.e., cardiac biomarkers, hemoglobin, platelet count, white blood cell [WBC]), and ST treatment (i.e., drug-eluting stent [DES] vs. bare-metal stent and anticoagulant with rivaroxaban vs. placebo).

Results:
Among 8,741 stented patients, a total of 155 ST events (2.25%) occurred by day 720. The cumulative incidence of early, late, and very late ST was 0.80%, 0.81%, and 0.77%, respectively. After multivariable adjustment, age ≥75 years (HR=2.13 [95% CI: 1.26-3.60]), a history of prior myocardial infarction (MI) (HR=1.81 [95% CI: 1.22-2.68]), low hemoglobin (HR=2.34 [95% CI: 1.59-3.44]), high WBC (HR=1.58 [95% CI: 1.02-2.46]), DES (HR=0.56 [95% CI: 0.38-0.83]), and rivaroxaban (HR=0.63 [95% CI: 0.44-0.88]) were associated with overall ST. Low hemoglobin (HR=2.35 [95% CI: 1.34-4.12]) and high WBC (HR=2.11 [95% CI: 1.17-3.81]) were predictive of early ST. Low hemoglobin (HR=2.32 [95% CI: 1.26-4.27]), prior MI (HR=2.98 [95% CI: 1.67-5.31]), and DES (HR=0.33 [95% CI: 0.16-0.67]) were associated with late ST. Age ≥75 years was predictive of very late ST (HR=3.71 [95% CI: 1.12-12.3]).

Conclusions:
The study identified factors with positive and negative associations with early, late, and very late ST that may be useful in constructing risk assessment models for ST.
Abstract 9166: Serum Level of Membrane Type 1-Matrix Metalloproteinase Inversely Corelates With Right Ventricular Systolic Pressure and Mean Pulmonary Artery Pressure in Pulmonary Hypertension
Authors: Sugimoto Koichi , Misaka Tomofumi , Yoshihisa Akiomi , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika
Published: April 2024

Introduction:
Pulmonary hypertension (PH) is defined as mean pulmonary arterial pressure (mean PAP) ≥ 25 mmHg and characterized by pulmonary vascular remodeling. Although right heart catheterization is essential for a definite diagnosis of PH, it is difficult to perform on all patients. Therefore, it is important to determine the new biomarker that predicts pulmonary arterial pressure. It has been reported that matrix metalloproteinase is associated with pulmonary vascular remodeling. Therefore, in this study, we focused on serum level of membrane type 1-matrix metalloproteinase (MT1-MMP) and examined its relationship with the hemodynamic indices in PH patients.

Methods:
Study subjects consisted of 44 patients with PH (idiopathic pulmonary arterial hypertension 9, chronic thromboembolic pulmonary hypertension 35). Serum level of MT1-MMP was measured by ELISA within 1 week before or after right heart catheterization.

Results:
The mean values of hemodynamic indices and MT1-MMP concentration of all patients were as follows: mean right atrial pressure, 6.5 ± 4.3 mmHg; right ventricular systolic pressure (RVSP), 74.0 ± 14.9 mmHg; mean PAP, 45.2 ± 9.5 mmHg; cardiac index, 2.5 ± 0.63 L/min/m
2
; pulmonary vascular resistance, 10.0 ± 4.1 Wood unit; pulse pressure (PP), 46.4 ± 11.2 mmHg; MT1-MMP, 0.383 ± 0.082 ng/ml. MT1-MMP inversely correlated with RVSP, mean PAP, and PP (RVSP, R = -0.405, P < 0.01; mean PAP, R = -0.316, P < 0.05; PP, R = -0.413, P < 0.01).

Conclusions:
Our results suggested that MT1-MMP might be a new biomarker reflecting the right ventricular pressure overload in pulmonary hypertension.
Abstract 9173: Perioperative Change in Left Ventricular Systolic Function Predicts Long-Term Mortality After CABG
Authors: Downey Michael , Hooks Matthew , Gravely Amy , Naksuk Niyada , Buelt-Gebhardt Melissa , Carlson Selma , Tholakanahalli Venkatakrishna N , Adabag Selcuk
Published: April 2024

Introduction:
Nearly 1/3
rd
of patients undergoing CABG have concurrent left ventricular systolic dysfunction (LVEF<50%). But the perioperative changes in LVEF is not well understood in these patients.

Hypothesis:
We hypothesized that patients with preoperative LV systolic dysfunction would have an improvement in LVEF post-CABG.

Methods:
We studied 549 patients with LVEF<50% who underwent CABG as part of the Surgical Treatment for Ischemic Heart Failure (STICH) trial and had pre- and post-operative (at 4 months) LVEF assessment using the same cardiac imaging modality. All imaging tests were interpreted at a core lab. Patients were classified into 3 groups according to change in LVEF: improved (>5% increase), unchanged, and worsened (>5% decrease).

Results:
Of the 549 patients (mean age 61.4±9.6 years, 13% women), 240 (43.7%) had improved LVEF (from 25.9±8.6% to 39.5±10.5%; p<0.001), 220 (40.1%) had unchanged, and 89 (16.2%) had worsened LVEF (from 34.4±7.8% to 23.6±7.8%; p<0.001) following surgery (Figure). On multivariate logistic regression, improvement in LVEF was inversely associated with baseline LVEF (OR 0.74, p<0.0001) and prior myocardial infarction (OR 0.56, p=0.028), but had a positive association with age (OR 1.10, p=0.045) and concurrent surgical ventricle restoration (OR 1.93, p=0.0004). Most notably, a >5% decrease in LVEF post-CABG was associated with higher long-term mortality (log-rank p=0.019).

Conclusions:
Almost 50% of patients with LV systolic dysfunction had a significant improvement in LVEF after CABG. However, 16% of patients, who had worsened LVEF perioperatively had a higher long-term mortality risk and may benefit from further investigation.