bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14694: Effect of Saphenous Vein Graft on Multiple Arterial Grafting Survival
Authors: Ren Justin , royse colin , Boggett Stuart , Royse Alistair
Published: June 2023

Introduction:
Saphenous vein graft (SVG) is associated with increased mortality and adverse cardiac events compared to arterial conduits, but uncertainty exists whether its presence would influence the outcome in multiple arterial revascularization (MAG).

Hypothesis:
That use of SVG adversely affects survival even in the setting of MAG.

Methods:
All patients undergoing primary isolated CABG between June 2001 to Jan 2020 were identified through a national registry. Exclusion criteria were reoperations, concomitant or previous cardiac surgery, and the absence of arterial grafting. The primary outcome was long-term mortality reported as time-to-event from the date of the operation. We performed a complete case retrospective comparison between MAG and single arterial grafting (SAG). Additional analysis was performed in MAG patients with or without SVG.Propensity score matching (PSM) and Cox proportional hazard model were used with significance defined as two-tailed P<0.05.

Results:
A total of 72,444 eligible patients had 58,629 (80.9%) males with 32,966 SAG (45.5%) and 39,478 MAG (54.5%). Two PSM was used to generate 29,354 matched pairs for SAG vs. MAG and 12,314 matched pairs for MAG with or without SVG. At a mean follow-up duration of 6.7 years, long-term mortality was significantly lower for MAG than SAG (HR, 0.89; 95% CI, 0.85-0.93). The cumulative Kaplan-Meier survival was 60.6% for SAG and 63.3% for MAG at 15 years postoperative, (P=0.002). In the comparison of MAG with or without SVG, the group without SVG (total arterial revascularization) had a lower risk of late mortality (HR, 0.91; 95% CI, 0.85-0.96). The interaction term analysis confirmed a significant effect for the presence of vein graft on the observed mortality when using MAG, (P=0.02). Sensitivity analyses produced consistent outcomes as the primary investigation.

Conclusions:
Multiple arterial grafting is associated with significantly improved long-term survival compared to single arterial grafting, and when total arterial revascularization was achieved, there was an incremental survival benefit.
Abstract 14714: Marked Gradient Reduction Through a Transcoronary Alcohol Ablation of Septal Hypertrophy in a Patient With Cardiac Amyloidosis and Hypertrophic Cardiomyopathy
Authors: Isaac Daniel M , Klingel Karin , Landmesser Ulf , Heidecker Bettina
Published: June 2023

A 66-year-old male with a history of carpal tunnel syndrome and hypertension presented with dyspnea (NYHA III), angina pectoris, and sinus bradycardia. On clinical examination, the patient was stable and euvolemic. A systolic murmur (III/VI) was audible in the 4th left intercostal space laterally, augmented after a Valsalva maneuver. An electrocardiogram revealed normal sinus rhythm, heart rate of 81 bpm, normal voltage, and non-specific ST-changes in I, II, III, aVF, V5, and V6. The patient underwent a transthoracic echocardiography, which revealed thickened ventricular walls (IVSd 23 mm, PWd 20 mm), hyperdynamic left ventricular ejection fraction (LVEF 75%), LVOT gradient of 150 mmHg maximum (after Valsalva maneuver), apical sparing on strain analysis, and a dilated atria. A coronary angiography ruled out coronary artery disease. A endomyocardial biopsy revealed hypertrophic cardiomyopathy combined with focal cardiac amyloidosis (Figure 1). Subtyping and genetic analysis revealed transthyretin (ATTR) wild-type amyloidosis. Accordingly, therapy with Tafamidis 61 mg daily was initiated. Given the relevant amount of hypertrophy depicted on the biopsy samples, the high LVOT gradient, and the patient’s debilitating symptoms despite maximal medical therapy, the decision was made to attempt a transcoronary alcohol ablation of the septal hypertrophy (TASH). The TASH reduced the LVOT gradient from 150 mmHg to 35 mmHg. After the procedure, the patient experienced significant symptom improvement (NYHA II) and was discharged the next day. This case illustrates the feasibility of marked LVOT gradient reduction in patients with amyloidosis and hypertrophic cardiomyopathy through a TASH procedure.
Figure 1:
Histology reveals hypertrophic cardiomyocytes and cardiac amyloidosis on Congo red staining.
Abstract 14723: A Rare Case of Constrictive Pericarditis: Inflammatory Myofibroblastic Tumor
Authors: Majid Muhammad , Parker Joshua , Kumar Ashwin , Mazumder Samia , Syed Alveena , Klein Allan L
Published: June 2023

Case Presentation:
A 14-year-old female presented with a 3-week history of lower extremity edema, abdominal distension, fatigue, and dyspnea on exertion. Her examination was notable for an elevated jugular venous pulse, abdominal distension with hepatomegaly, and 2+ pitting edema in the bilateral lower extremities. Laboratory findings were within normal limits. EKG showed low-amplitude QRS and echocardiogram confirmed bi-atrial enlargement, a dilated and non-compressible IVC, dyskinetic interventricular septum, and elevated right atrial pressures. Chest computed tomography demonstrated mediastinal mass with findings of a 6.2 x 4-centimeter mass in the pre-vascular space, diffuse necrotic mediastinal lymphadenopathy, and constrictive pericarditis with associated congestive hepatopathy. Cardiac magnetic resonance imaging revealed significant enhancement in T2 STIR with severe circumferential delayed enhancement, diastolic bounce, and respirophasic shift. A right heart catheterization was pursued which revealed elevated filling pressures but preserved cardiac index. The patient underwent video-assisted thoracoscopic biopsy of the mass with an initial histologic diagnosis of inflammatory myofibroblastic tumor (IMT). She underwent radical pericardiectomy for symptom resolution.

Discussion:
IMT is composed of spindle cells mixed with infiltrates of varying numbers of inflammatory cells. Although IMT can present in any age group, most patients who develop IMT are in adolescence. IMT is incredibly rare and its etiology still remains unclear. It remains difficult to distinguish IMT from a malignant tumor on the basis of imaging. As a result, in most cases, a definitive diagnosis is made based on the histopathological findings from either a resected tumor or a needle biopsy. Management of IMTs presents a challenge as treatment protocols have not clearly been established; radical local excision of the tumor is the mainstay of treatment.
Abstract 14726: Serial Assessment of Cardiac Biomarkers and Risk of Cardiovascular Death or Hospitalization for Heart Failure in DECLARE-TIMI 58
Authors: Berg David D , Wiviott Stephen D , Raz Itamar , Jarolim Petr , Goodrich Erica , Mosenzon ofri , Cahn Avivit , Bhatt Deepak , Leiter Lawrence , McGuire Darren K , WILDING JOHN , Gause-nilsson Ingrid A , Sabatine Marc S , Morrow David A
Published: June 2023

Introduction:
Circulating cardiovascular (CV) biomarkers, including N-terminal pro-B type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT), are associated with risk of heart failure (HF) events in patients (pts) with type 2 diabetes (T2D). Less is known about the prognostic significance of changes in these biomarkers over time or the early effects of the SGLT2i dapagliflozin (dapa) on these markers.

Methods:
DECLARE-TIMI 58 was a randomized, placebo-controlled trial of dapa in 17,160 pts with T2D (median f/u = 4.2y). NT-proBNP & hsTnT (Roche) were measured at baseline & 6 mo. The outcome of interest was CV death (CVD) or hosp for HF (HHF). Outcome analyses were performed from a landmark of the 6-mo study visit with pts categorized by change in each biomarker over the first 6 mo. Hazard ratios were adjusted for baseline biomarker value, randomized treatment, age, sex, race, smoking, eGFR, prior HF, BMI, T2D duration, insulin use, CAD, prior MI, ischemic stroke, PAD, dyslipidemia, & hypertension. Linear mixed models were used to assess the effect of dapa on log-transformed NT-proBNP & hsTnT.

Results:
Serial NT-proBNP & hsTnT values were available in 13,459 pts (78%). Among pts allocated to placebo (n=6,698), NT-proBNP was more dynamic than hsTnT (≥20% change from baseline in 71% vs. 33% of pts; p<0.001). In the full cohort, independent of randomized treatment, there was a stepwise graded relationship between change in NT-proBNP & hsTnT and risk of CVD/HHF, whereby increases in either biomarker were associated with higher risk and decreases in either biomarker were associated with lower risk (p-trend for adj-HR <0.001 for each). Considered together, changes in the 2 markers were complementary (
Fig
; p<0.001). Dapa significantly reduced NT-proBNP (relative LS mean change, -6% [-4% to -8%]; p<0.001) but not hsTnT (0% [-1% to +1%]; p=0.92) over 6 mo.

Conclusions:
Early changes in hsTnT & NT-proBNP are associated with subsequent risk of CVD/HHF in pts with T2D.
Abstract 14740: Racial Disparities in Adverse Pregnancy Outcomes and Cardiovascular Health After Delivery: A Mediation Analysis in Numom2b-hhs
Authors: Petito Lucia , Huang Xiaoning , Bairey Merz C. Noel , Bello Natalie A , Catov Janet , Chung Judith , Lane-Cordova Abbi D , Haas David , Levine Lisa D , McNeil Rebecca , Miller Eliza C , Saade George , Theilen Lauren , Wiener Laura E , Yee Lynn , Greenland Philip , Grobman William , Khan Sadiya S
Published: June 2023

Introduction:
Racial disparities in risk of adverse pregnancy outcomes (APOs) and cardiovascular health (CVH) after delivery are well-established. Therefore, we sought to quantify the extent to which APOs explained racial differences in CVH.

Methods:
We included non-Hispanic (NH) Black and NH White individuals from the prospective, longitudinal nuMoM2b-HHS cohort. Race and ethnicity, which represent social constructs, were self-reported. APOs (hypertensive disorders of pregnancy [HDP], small for gestational age [SGA], preterm birth [PTB], and gestational diabetes mellitus [GDM]) were centrally adjudicated via medical records. The primary outcome was CVH score based on 4 metrics: body mass index, blood pressure, cholesterol, and glucose assessed at follow-up. Using a life-course approach, APOs were considered on the pathway between racial identity and CVH. Mean difference in CVH score was estimated via targeted maximum likelihood estimation (TMLE). Sensitivity analyses included alternative causal inference methods. All models were adjusted for age, study site, insurance, and fetal sex.

Results:
Among 2,987 birthing individuals, NH Black individuals were significantly more likely than NH White individuals to experience HDP, SGA, and PTB, and had lower (worse) CVH scores at follow-up (mean difference 0.52 [0.38-0.66]). Counterfactual disparity measures were estimated, which represent the adjusted racial difference in CVH score that would remain if no one experienced a particular APO (
Table
). Approximately 2% of the racial difference in CVH scores was due to racial differences in APOs when estimating with TMLE. Similar estimates were observed with other methods.

Conclusions:
A small proportion of the racial disparity in CVH years after delivery was mediated via APOs. Mitigating racial inequities in CVH will require interventions upstream of the first pregnancy (before an APO occurs) in addition to downstream risk factor control.
Abstract 14745: Recurrent Cardiogenic Shock Secondary to Shoshin Beriberi in s Patient With Heavy Alcohol Use
Authors: Asturias Karla M , Sangoi Matthew , Kinniry Paul , Gandler Alan
Published: June 2023

Introduction:
Thiamine is an essential enzyme cofactor in cellular metabolism. Its deficiency can manifest as wet beriberi with high-output heart failure. Its more severe and fulminant form is known as shoshin beriberi, characterized by cardiogenic shock, hemodynamic collapse, and multiorgan failure.

Case Description:
A 67-year-old male presented with dyspnea on exertion and orthopnea. On exam, he was tachycardic and cold to the touch. Initial workup showed metabolic acidosis, elevated lactate, acute kidney and liver injury, and elevated NT proBNP. ECG showed atrial fibrillation with RVR. His past medical history included heavy alcohol use and a similar presentation two years prior with new-onset heart failure complicated by shock and acute kidney injury, requiring CRRT. At that time, he improved with high-dose thiamine and decompensation was attributed to shoshin beriberi.

Shortly after admission, the patient developed worsening shock, with liver failure, renal failure, and DIC. He was started on pressors, broad-spectrum antibiotics, high-dose thiamine and CRRT. TTE showed biventricular dysfunction and global hypokinesis with LVEF of 20%. Hemodynamic monitoring was consistent with cardiogenic shock. Infectious workup was negative. Within 96h of the initiation of thiamine, the patient’s mental status and hemodynamics significantly improved, with resolution of cardiogenic shock. He remained hemodynamically stable, his laboratory abnormalities improved, and he was started on GDMT. He required intermittent HD for several months, after which it was discontinued. He later underwent LHC that showed nonobstructive CAD.

Discussion:
The diagnosis of shoshin beriberi is challenging and requires a high index of suspicion for presumed thiamine deficiency, particularly in critically ill patients with many comorbidities. An empiric therapeutic trial of thiamine supplementation in this group of patients can lead to improvement of hemodynamics within hours to days, as in this case. Even though his LVEF has not yet fully recovered, we suspect that his presentation was due to an acute-on-chronic insult, in the setting of alcohol-induced cardiomyopathy. To the best of our knowledge, this is the first report of recurrent shoshin beriberi in the literature.
Abstract 14746: Pulse Pressure More Strongly Associates With Subclinical Myocardial Injury Than Do Systolic and Diastolic Blood Pressures
Authors: Young Juliet , Lyngbakken Magnus N , Hveem Kristian , Rørvik Røsjø Helge , Omland Torbjorn
Published: June 2023

Introduction:
Long-standing hypertension is associated with subclinical myocardial injury expressed as chronically elevated cardiac troponin concentrations. Subclinical myocardial injury and subsequent diffuse myocardial fibrosis may represent important intermediaries between hypertension and risk of heart failure and cardiovascular (CV) death. The relative strength of the associations between systolic blood pressure (BP), diastolic BP and pulse pressure and subclinical myocardial injury is unknown.

Aim:
To assess the relative impact of systolic BP, diastolic BP and pulse pressure on subclinical myocardial injury.

Methods:
Cardiac troponin I (cTnI) was measured by a high-sensitivity assay (Abbott Diagnostics) in 32,968 participants of the fourth wave of the Trøndelag Health Study (HUNT4) from 2017 to 2019. The longitudinal substudy included participants from HUNT4 who also had BP measurements from the third wave of HUNT (HUNT3) from 2006 to 2008. This included 18,681 study participants. All study participants with a history of CV disease were excluded prior to analysis. We defined subclinical myocardial injury as cTnI ≥4ng/L for women and ≥6ng/L for men, and used logistic regression models adjusted for established CV risk factors.

Results:
The mean age was 52 (SD±17) years, and 56.9% were female. Cross-sectionally, pulse pressure was more strongly associated with subclinical myocardial injury (adjusted odds ratio [aOR] 1.08, 95% confidence interval [CI] 1.06-1.10) compared to systolic BP (aOR 1.05, 95% CI 1.04-1.06) and diastolic BP (aOR 1.02, 95% CI 0.99-1.04). Longitudinally, change in diastolic BP was the only BP variable associated with subclinical myocardial injury (aOR 1.03, 95% CI 1.01-1.06), compared to change in systolic BP (aOR 1.01, 95% CI 0.99-1.02) and change in pulse pressure (aOR 0.99, 95% 0.97-1.01, p for all comparisons < 0.05).

Conclusions:
At a given time, pulse pressure is the superior BP variable in predicting subclinical myocardial injury. Over time, only change in diastolic BP is associated with subclinical myocardial injury. High pulse pressure and longitudinal changes in diastolic BP could represent hypertension phenotypes at high risk for subclinical myocardial injury and subsequent increased CV risk.
Abstract 14748: Genetic and Neurobiological Factors Link Chronic Stress to Earlier Onset Hypertension
Authors: Grewal Simran , Mezue Kenechukwu , Abohashem Shady , Zureigat Hadil , Gharios Charbel , Cardeiro Alexander , Liu Zhaowen , Choi Karmel , Smoller Jordan , Osborne Michael , Tawakol Ahmed A
Published: June 2023

Introduction:
Chronic stress conditions associate with a greater incidence of hypertension (HTN).

Hypothesis:
We tested whether genetic risk for or neurobiological features of vulnerability to chronic stress associate with the risk for and timing of HTN.

Methods:
Data were obtained from Mass General Brigham Biobank participants. HTN was defined as
>
2 International Classification of Disease codes at least one week apart. Those with secondary HTN and those diagnosed at age <18 years were excluded. Of this parent dataset, a validated polygenic risk score for neuroticism reflecting stress sensitivity (ssPRS) was assessed in 11,320 participants. Of the same parent dataset, stress-related neural network activity (SNNA), defined as a ratio of amygdalar to regulatory medial prefrontal cortical activity, was measured in 867 individuals who had undergone clinical
18
F-flurodeoxyglucose positron emission tomography imaging.

Results:
In the genetic subgroup, the median age [interquartile range] of participants was 60 [34-86] years and 56.3% were female. In a Cox regression model, standardized ssPRS predicted incident HTN (hazard ratio [95% confidence interval (CI)]: 1.05 [1.02, 1.08], p<0.001), when adjusted for principal components, age, and sex (Figure 1A). Similarly, standardized SNNA predicted incident HTN (1.44 [1.11, 1.85], p = 0.006) when adjusted for age and sex. The age of onset of HTN was significantly lower in those with high vs. low ssPRS (difference (years) [95% CI]: -1.65 (-2.45, -0.85], p < 0.001) and in those with high vs. low SNNA (-4.67 [-7.68, -1.66], p = 0.002, Figure 1B) in unadjusted models with findings of a similar magnitude and significance in multivariable models.

Conclusions:
This study identifies genetic and neurobiological factors linking chronic stress to HTN risk and its age of onset. Future studies should evaluate whether therapies targeting this neurobiological pathway may reduce HTN risk.
Abstract 14754: Peak Frequency Mapping in Low Voltage Zones Can Identify the Critical Isthmus in Atypical Atrial Flutters
Authors: Karatela Maham , Dowell Robert , Friedman Daniel , Thomas Kevin L , Jackson Kevin , Piccini Jonathan P
Published: June 2023

Introduction:
Atypical atrial flutters (AFL) are a heterogeneous group of reentrant arrhythmias and can be challenging to map. Peak frequency (PF) mapping is a novel method of identifying local conductivity and may help identify critical portions of myocardial substrate supporting reentry.

Hypothesis:
The critical isthmuses of left atrial (LA) AFLs demonstrate a combination of low-voltage and high PF.

Methods:
LA omnipolar voltage and PF maps were generated using the EnSite Precision Mapping System and HD-Grid catheter in 13 patients undergoing AFL ablation. For the purpose of this study, mapping was performed during AFL and normal voltage was defined as ≥ 0.5 mV, low-voltage (LV) 0.1 - 0.5 mV, and scar < 0.1 mV. PF distributions were analyzed in each tissue type. Conduction velocity (CV) was characterized across PF with correlational analysis. The 1-cm radius from sites of arrhythmia termination with ablation were analyzed to characterize mean PF and voltage in nearby myocardial tissue.

Results:
Mean age was 65.8 ± 9.3 years and 54% were female. A total of 37,331 points were analyzed. Sites of slow conduction included the mitral isthmus (46%), LA roof (23%), pulmonary vein antra (15%), posterior wall (8%), and anterior wall (8%). In normal voltage tissue, mean PF was 337.7 ± 115.4 Hz. LV and scar tissue had left-skewed PF distributions and lower mean PF (
p
< 0.0001). While CV had no trend across PF in tissue with normal voltage (

R
2

, 0.0002 to 0.1), there was moderate conduction slowing at higher PF in LV tissue (
R
2
, 0.07 to 0.30). In PF-LV overlay maps, all termination sites resided in regions of LV and high PF (
Figure
). Of the 1-cm areas neighboring termination, 77% had significantly higher PF than the global LA (
p
< 0.05), of which 80% had significantly lower mean voltage (
p
< 0.01) or mean voltage < 0.5 mV.

Conclusions:
Sites of arrhythmia termination can be identified in LV tissue at higher PF. Low-voltage, high-PF areas may be critical targets during catheter ablation of atypical AFL.
Abstract 14764: Cardiac Cta Utilization for Chest Pain Stratification Increased During and After the Covid-19 Pandemic: Experience of a Latin-American Center
Authors: Medina-Rincon German J , Gallo Sebastian , Valderrama Achury Maria Daniela , Castañeda Joaquin , Abigail Montanez Dickens , Salazar Castro Gabriel , Gutierrez Claudia , Marín Victor , Jaimes Castellanos Claudia Patricia , Forero Julian Francisco , Medina Hector
Published: June 2023

Introduction:
During the COVID-19 pandemic, stratification of patients with chest pain with low-to-moderate probability of CAD (LMCP) became problematic due to fear of infection. We analyzed the impact in volume trends of modalities for stratification in these patients -including stress echocardiography (S-TTE), cardiac computed tomography (CCT), and single-photon emission CT (SPECT)- before, during, and after the pandemic

Hypothesis:
Usage of CCT increased during the COVID-19 pandemic due to the lower exposure of patients, during this test, to healthcare personnel.
Methods: R
etrospective chart review conducted between 2019 and 2021. We defined 3-time frames: pre-pandemic period (1/1/2019-12/31/2019), pandemic period (1/1/2020-12/31/2020), and post-pandemic period (1/1/2021-12/31/2021). The study included data of all 3 mentioned imaging modalities.

Results:
Our cohort included 19,637 LMCP patients evaluated using 1,369 CCTs (7%), 2,380 S-TTEs (13.6%) and 15,588 SPECTs (79.4%) -Fig 1a-. During the pre-pandemic period, CCT studies corresponded to 3.0%, while S-TTE and SPECT corresponded to 14.7% and 82.4%, respectively. In the post-pandemic period, CCT studies corresponded to 9.8%, while S-TTE and SPECT corresponded to 12.3% and 77.9%, respectively. An upward variation was observed regarding the utilization of CCT in the post-pandemic period compared to the pre-pandemic period (p<0.001), and a downward change was observed in S-TTE when the post-pandemic period was compared with the pre-pandemic period (p<0.001) -Fig 1b-.

Conclusions:
Since the beginning of the COVID-19 pandemic, the utilization of SPECT and s-TTE in LMCP patients decreased compared to the pre-pandemic period. In the post-pandemic period, both tests increased in use although their volumes are lower compared to the pre-pandemic period. Conversely, CCT had a linear increase since the beginning of the pandemic and this pattern has extended to the post-pandemic period.
Abstract 14772: Comparing Efficacy of Venous Closure Devices in Patients Undergoing Atrial Fibrillation and Atrial Flutter Ablation: A Retrospective Review
Authors: Ahmed Adnan , Garg Jalaj , Charate Rishi , Pothineni Naga Venkata K , Gopinathannair Rakesh , Natale Andrea , Lakkireddy Dhanunjaya
Published: June 2023

Introduction:
Vascular closure devices have shown marked improvement in patient comfort and time to ambulation after undergoing atrial fibrillation (AF) and atrial flutter (AFL) radiofrequency ablation. They have been proven superior to manual closure and Figure of 8 suture in terms of pain control and time to ambulate. However, data comparing different vascular closure devices is sparse.

Hypothesis:
To compare the efficacy of venous closure devices

Methods:
We retrospectively reviewed 100 patients at our institution who underwent AF and AFL radiofrequency ablation. We aimed to assess the difference in time to ambulation, device failure, pain control and vascular complication rate between the two commonly used venous closure devices (VASCADE and PERCLOSE).

Results:
A total of 100 patients (50 in each arm) were included in the study. The mean age was 67.6
+
9.3 years and 73% patients were men. The two groups were well balanced with respect to baseline demographics and clinical characteristics except for coronary artery disease (24%
VASCADE vs. 14% PERCLOSE, p <0.001).
No significant difference was observed in time to ambulate between PERCLOSE (2
+
0.21 hours) vs VASCADE (2
+
0.23 hours); p=0.74. 8% patients (n=4) in VASCADE arm required additional PERCLOSE to achieve hemostasis. 4% (n=2) patients in PERCLOSE arm required opioids for pain management; compared to none in VASCADE arm. No closure device related complications were observed in either arm.

Conclusions:
Both venous vascular closure systems offer similar efficacy in terms of time to ambulate. However, PERCLOSE was used in addition to VASCADE in a few instances to achieve hemostasis.
Abstract 14781: Simultaneous Profiling of Genotype and Transcriptome at Single Cell Resolution Identifies Cellular Programs Underlying Clonal Hematopoiesis Pathology
Authors: Heimlich Brett , Bhat Pawan , Parker Alyssa C , Ulloa Jessica , Olson Sydney , Ferrell P. Brent , Bick Alexander G
Published: June 2023

Introduction:
Clonal hematopoiesis of indeterminate potential (CHIP) results from a clonal expansion of hematopoietic stem cells due to somatic mutations in genes such as DNMT3A or TET2. Patients with CHIP have poor cardiovascular outcomes. TET2 CHIP clones that make up >20% of blood increases risk. Whether CHIP mutated cells confer risk directly or through polarizing other cells is presently unknown as prior work has been unable to simultaneously resolve mutational status and transcriptome of an individual cell.

Methods:
We performed single cell RNA-seq on blood from patients with DNMT3A CHIP (N=9), TET2 CHIP (N=8), and controls (N=6). We identified individual cell CHIP mutational status with a novel method that leverages mitochondrial mutations to identify cell lineage.

Results:
Across 104,556 single cells, CHIP patients had a higher proportion of CD14 monocytes (32% vs. 18%). Within individuals, CHIP mutated cells exhibited a strong myeloid bias. At the extreme, 93% of TET2 mutated cells were monocytes in one patient. Comparing TET2 CHIP monocytes to controls identified a hyper-inflammatory phenotype with increased expression of inflammatory cytokines and their downstream targets, and elevated expression of adhesion molecules. Comparing TET2-mutated CD14 monocytes to unmutated monocytes within the same individual localized the inflammatory phenotype to the mutated cells. Conversely, this phenotype was not observed in DNMT3A CHIP monocytes either in aggregate or within the same individual.

Conclusions:
Simultaneous, high-throughput, single-cell resolution of DNA mutation status and RNA transcriptomes identifies aberrant cellular programs in TET2-mutated CD14 monocytes. Our data support a simple mechanistic model for CHIP cardiovascular disease risk that is proportional to the number of mutated cells present. Differences observed between TET2 and DNMT3A provide a potential explanation for the differential pathogenicity of these two mutations.
Abstract 14790: Impact of Pre-Frailty and Frailty in Women Undergoing TAVR: Insights From the WIN-TAVI Registry
Authors: Petrovic Marija , Spirito Alessandro , Sartori Samantha , Snyder Clayton , Vogel Birgit , Nicolas Johny , Cohen Rebecca M , Cao Davide , Tchetche Didier , Petronio Anna S , Mehilli Julinda , Lefevre Thierry , Presbitero Patrizia , Capranzano Piera , IADANZA ALESSANDRO , Sardella Gennaro , Van Mieghem Nicolas M , meliga emanuele , DUMONTEIL Nicolas , Fraccaro Chiara , Trabattoni Daniela , Mikhail Ghada , Ferrer-Gracia Maria-Cruz , Naber Christoph , Kievit Peter C , Sharma Samin K , Morice Marie C , Dangas George , Chieffo Alaide , Mehran Roxana
Published: June 2023

Background:
Frailty has been shown to significantly affect outcomes after transcatheter aortic valve replacement (TAVR). The impact of pre-frailty on TAVR outcomes in women is still unclear.

Aim:
To assess the impact of pre-frailty and frailty on outcomes in women enrolled in the Women's InterNational transcatheter aortic valve implantation (WIN-TAVI) registry.

Materials and methods:
WIN-TAVI was a multinational, prospective, observational registry, which enrolled women at intermediate or high preoperative risk undergoing TAVR. Patients included in this registry were divided into three groups, based on the number of fulfilled Fried frailty criteria: non-frail (no criteria, reference group), pre-frail (1-2 criteria) and frail (≥3 criteria). The primary outcome was the Valve Academic Research Consortium (VARC)-2 efficacy endpoint at 1-year after TAVR. The key secondary outcome was VARC-2 safety endpoint.

Results:
Out of 1,019 patients, 264 (25.9%) were pre-frail and 33 (3.2%) frail. The risk of VARC-2 efficacy endpoint at 1-year was increased in pre-frail (19.7%, HR 1.36, 95% CI 0.98-1.89) and frail (24.2%, HR 1.74, 95% CI 0.85-3.57) as compared to non-frail patients (14.9%, reference group), although it didn’t reach statistical significance. The risk of VARC-2 safety endpoint was significantly higher in pre-frail (25.8%, HR 1.43, 95% CI 1.07-1.91) and frail (42.4%, HR 2.77, 95% CI 1.60-4.80) than in non-frail subjects (19%, reference group); this difference was driven by an excess of major vascular complications and life-threatening or major bleeding in the pre-frail and frail group. In addition, in pre-frail patients hospitalizations for heart failure or valve-related symptoms at 1-year were higher than in non-frail patients.

Conclusion:
In women at intermediate or high preoperative risk undergoing TAVR, pre-frailty and frailty increased the risk of safety endpoints such as vascular complications and major bleeding.
Abstract 14796: Fifteen-Year Trend in Antiplatelet Treatment Among Drug-Eluting Stent Recipients: Newer Drugs Are Replacing the Older Ones
Authors: Kim Sunwon , Lee Jong-Seok , Song Woo Hyuk
Published: June 2023

Backgrounds:
Drug-eluting stent (DES) recipients require 6-12-month P2Y12 inhibitor (P2Y12i)-based dual antiplatelet treatment (DAPT) and long-term aspirin mono antiplatelet treatment (MAPT). Given the diversity of contemporary antiplatelet agents, antiplatelet treatment (APT) selection is becoming more complicated in this patient population. Herein, we evaluated 15-year APT trends among DES recipients nationwide.

Methods:
Nationwide prescription data of 79,654 patients who underwent percutaneous coronary intervention (PCI) using DESs from 2002 to 2018 in Korea were analyzed. APT claim data were collected longitudinally at multiple time-points post-PCI. Fifteen-year longitudinal APT pattern changes were analyzed at 3-year intervals.

Results:
DAPT (80.7%) was the most preferred initial APT, followed by MAPT (7.8%) at 3 months post-PCI. A substantial number of patients received prolonged DAPT post-PCI (3 years: 41.0%; 10 years: 27.7%). There was a noticeable delay in DAPT-to-MAPT conversion from the mid- to late-2000s; the conversion was similar during the 2010s, occurring most robustly at 12-18 months post-PCI. Clopidogrel had long and increasingly been used for long-term MAPT, surpassing aspirin from 2013-2015. Recent increases in newer P2Y12i (mostly ticagrelor) prescription were noted. However, P2Y12i use was still low (2013-2018: 25.8%) and peaked immediately post-PCI. The patients treated with newer P2Y12is were more likely younger men and presented with acute myocardial infarction, suggesting that physician-directed newer P2Y12i use remained limited to patients with low bleeding risks.

Conclusions:
Real-world APT is evolving, however guideline-practice gaps exist. Newer drugs were replacing the older ones, even challenging role of aspirin as chronic maintenance monotherapy. Further studies exploring the impact of diverse APT strategies on patient outcomes are expected to provide insights into optimal APT that can sophisticatedly balance the ischemic and bleeding risks.
Abstract 14801: Protective Associations of Dairy Foods and Cardiometabolic Markers Differ by Food Type and Fat Content: The Boston Puerto Rican Health Study
Authors: Mangano Kelsey M , Kenny Sophie , Zhang Xiyuan , Bigornia Sherman , Mattei Josiemer , Tucker Katherine L
Published: June 2023

Introduction:
The relation of dairy intake with cardiometabolic (CM) markers remains unclear due to a complex nutrient profile across dairy types. This study aimed to evaluate associations between dairy intake and CM markers among Puerto Rican adults with excessive CM burden.

Methods:
Baseline and 2-y follow-up data on diet and CM markers were available for 1110 participants aged 46-78y. Diet was assessed with a validated food frequency questionnaire. Dairy groups (total, milk, yogurt, cheese, cream, total with any fat, total without fat) were created from disaggregated foods and presented as servings/d/2000 kcal (s/d). Mean dietary intakes across two visits were used. CM biomarkers were assessed from fasted blood at 2-y and included waist circumference (WC), HDL and LDL cholesterol, TG, insulin, HbA1c, HOMA-IR, homocysteine (Hcy), C-reactive protein (CRP), blood pressure (BP) and Framingham risk score (FRS). Generalized linear and logistic regression were used to determine associations between dairy variables and each CM marker, adjusted for age, sex, BMI, kcal, alcohol and fruit /vegetable intakes, CVD/diabetes medications, language acculturation score, smoking, perceived stress, and physical activity. Multiple comparisons were adjusted by FDR correction.

Results:
Mean age was 59.3±7.7y, 70% female, 80% with metabolic syndrome. Total dairy intake was 2.3±1.1 s/d; 2.1±1.0 from dairy with fat and 0.2±0.5 without fat. Total dairy, dairy with fat, and milk intakes were associated with lower Hcy (β -0.37, SE 0.12,
P
=0.0012; β -0.39, SE 0.13,
P
=0.003; β -0.42, SE 0.13,
P
=0.002; respectively); non-fat dairy with lower WC (β -1.41, SE 0.44,
P
=0.001); milk with lower odds of high BP (OR 0.84,
P
=0.04); cheese with lower TG (β -18.5, SE 9.2,
P=
0.04); yogurt with lower HbA1c (β -0.46, SE 0.17,
P
=0.008); cream with lower HbA1c (β -0.20, SE 0.10,
P
=0.04) and HOMA-IR (β -1.33, SE 0.56,
P
=0.02). No associations were seen with cholesterol, CRP, insulin, or TG. After FDR correction, findings remained significant for total dairy, dairy with fat, and milk with Hcy.

Conclusions:
Protective associations of dairy with specific CM markers vary by type of dairy and fat content. Associations were independent of overall dietary pattern and other risk factors for CM disease.
Abstract 14815: Clinical Prediction Model of Growth Rate in Type B Aortic Dissection Using 4D Flow MRI
Authors: Maroun Anthony , Jarvis Kelly , Baraboo Justin , Pradella Maurice , Weiss Elizabeth , Chu Stanley , Kilinc Ozden , Berhane Haben , mehta chris , Malaisrie S , Hoel Andrew , Markl Michael , Allen Bradley D
Published: June 2023

Introduction:
Chronic type B aortic dissection is often associated with aneurysmal degeneration and rupture of the descending aorta (DAo). Early identification of patients at risk for aneurysmal degeneration could identify candidates for prophylactic surgical intervention. Clinical and static imaging measures (age, early aortic dilation, etc.) have been unable to reliably predict DAo growth rate (GR). Importantly, these measures do not account for dissection hemodynamics, an important driver of GR. We therefore aimed to build a multivariate linear regression model that combines baseline clinical, morphologic, and hemodynamic metrics to predict GR.

Methods:
Patients who underwent 4D-flow MRI and had ≥9 months of imaging follow-up were identified. Baseline clinical features were obtained from medical records. Morphologic metrics were assessed on baseline imaging and GR (mm/y) was calculated by comparison to follow-up scans. Baseline 4D-flow MRI was used to measure the following parameters in the true lumen: pulse wave velocity (PWV), peak velocity (PV), and forward flow. False lumen thrombus (FLT) was assessed in percentage quartiles (0, 1-25%, 26-50%, 51-75%, >75%) and scored from 0 to 4. Stepwise multivariate regression was conducted to identify a model for best prediction of GR (Figure 1).

Results:
Thirty-four patients were included (70.0 ± 16.5y; 21 M). On multivariate analysis, we detected a model that significantly correlates with GR (r
2
= 0.55 p < 0.001) by using PWV, FLT, and PV as predictors. In fact, PWV was the strongest predictor overall (r = - 0.54 p = 0.001). Clinical features and other imaging measures showed no association with GR and hence were excluded by stepwise regression analysis.

Conclusions:
The regression model identified two hemodynamic parameters and FLT as the strongest predictors of GR. This finding suggests that a multitude of hemodynamic factors impact GR and that 4D flow parameters have the potential to improve clinical risk models.
Abstract 14824: Life-Space Assessment Score is a Prognostic Factor in Older Adults With Cardiovascular Disease
Authors: Hirashiki Akihiro , Shimizu Atsuya , Kokubo Manabu , Nomoto Kenichiro , Kondo Izumi , Arai Hidenori
Published: June 2023

Introduction:
Older adults with cardiovascular disease (CVD) often have multiple comorbidities. However, to our knowledge, no studies have investigated the association between prognosis and life-space assessment (LSA) score, an indicator of the degree of use of the surrounding home and wider environments by patients, in older adults with CVD. The aim was to investigate whether LSA scores were associated with prognosis in older adults with CVD.

Methods:
Eligible subjects were aged over 65 years (average age 79.2 ± 7.6 years; left ventricular ejection fraction 56.7% ± 13.2%) and had been admitted to our hospital for worsening CVD. Receiver operating characteristic (ROC) analysis determined the cutoff LSA score (0-120 points, with higher scores reflecting greater life-space activity) in cardiovascular hospitalization. The calculated cutoff value was used to investigate the relationship between LSA score and cardiovascular events by survival analysis (Kaplan-Meier method) and Cox proportional analysis. The points at each level are totaled to achieve LSA scores from 0 to 120, with higher scores reflecting greater life space activity.

Results:
Over a 2-year period there were 44 cardiovascular hospitalizations and 10 cardiovascular deaths. ROC analysis revealed that the cutoff LSA score in cardiovascular hospitalization was 53.0 points (sensitivity, 55.9%; specificity, 82.1%, P = 0.003). Cardiovascular hospitalization and mortality rates were significantly higher in the low LSA group (P < 0.001 for both,
Figure
). Cox proportional analysis revealed that low LSA score was independently associated with cardiovascular hospitalization (hazard ratio; 2.540, 95% CI; 1.135 to 5.680, P = 0.023) and cardiovascular death (hazard ratio; 15.223, 95% CI; 1.689 to 137.180, P = 0.015), even after adjustment for age, sex, and log-transformed BNP level.

Conclusions:
LSA score is associated with prognosis in older adults with cardiovascular disease.
Abstract 14840: Performance of Quality Measures for Patients With Heart Failure in a Learning Health System
Authors: Liu Albert Y , Lu Alice , Petito Lucia , Persell Stephen D , Gleason Lacey , Pawlowski Anna , Wu Tingqing , Tibrewala Anjan , Kho Abel , Smith Justin D , Mutharasan Raja K , Wilcox Jane E , Yancy Clyde W , Ahmad Faraz S
Published: June 2023

Introduction:
Distinguishing heart failure (HF) patients who have suboptimal care quality due to physiological limitations vs non-clinical reasons (i.e. clinical inertia) may facilitate deployment of limited resources in a learning health system. We sought to evaluate the impact of accounting for physiological limitations on quality measures (QMs) using electronic health record (EHR) data.

Methods:
We developed EHR-based QMs for guideline-directed medical therapies (GDMT) for patients with HF with reduced ejection fraction (HFrEF), adapted from the 2020 ACC/AHA report on quality measures. In a cohort of HFrEF patients from primary care and cardiology clinics at an integrated health system, we compared the 2021 monthly rate of prescription of beta blockers (BBs), ACEis/ARBs/ARNIs, mineralocorticoid receptor antagonist (MRAs), and SGLT2 inhibitors (SGLT2is), with and without available clinical exclusions based on vitals, renal function, and medical history.

Results:
A cohort of 4186 patients with HFrEF (mean age 69, 35% female, 18% Black) had at least one eligible encounter in 2021. The monthly prescription rates of GDMT were high for BBs (79.1-84.8%) and ACEIs/ARBs/ARNIs (69.1-77.0%), but low for MRAs (39.4-52.0%) and SGLT2is (6.9-23.2%). With the addition of clinical exclusions, the performance on each QM was higher for BBs (83.1-88.0%), ACEIs/ARBs/ARNIs (78.1-84.7%) MRAs (48.3-60.2%), and SGLT2is (8.8-28.7%) (Figure).

Conclusions:
The addition of EHR-based clinical exclusions resulted in higher QM performance and identified a narrower population that may benefit more from quality improvement strategies.
Abstract 14860: Quantitative Whole Blood Platelet Aggregation Predicts Occurrence of Subacute Thrombosis in Patients After Percutaneous Coronary Intervention
Authors: Funabashi Nobusada , Akaza Shin , Nakamura Kohki , Misumi Kazuo
Published: June 2023

Introduction:
The risk of subacute thrombosis (SAT) after percutaneous coronary intervention (PCI) is high if patients show high whole blood platelet aggregation.

Hypothesis:
For such high-risk patients, even though dual antiplatelet therapy is performed, whole platelet aggregation should be quantitated and if high, the indication for additional antiplatelet therapy determined.

Methods:
This is a retrospective analysis of 26,314 stents from 26,314 patients (20,028 males; mean age 70±11 years). The whole blood platelet aggregatory threshold index (PATI; WBA-Neo; ISK, Osaka, Japan) was calculated. PATI was used to determine the minimum concentration of adenosine 5'-diphosphate causing a non-reversible aggregation of platelets and indicated platelet aggregation (range 0-8 μM). The higher the PATI, the lower the platelet aggregation. All patients received single or double antiplatelet drug therapy according to physician choice.

Results:
SAT occurred in 35 (0.13%) of 26,314 patients after PCI. Total blood PATI was 5.25±2.46 in 35 patients with SAT and 7.14±1.75 in 26,279 patients without SAT (P<0.001). Receiver operating characteristic (ROC) curves of the PATI for detection of occurrence of SAT showed an area under the curve (AUC) of 0.721. Best cutoff point of PATI was 6.435μM (sensitivity of 81% and specificity of 66%) for detection of occurrence of SAT (Youden index=0.464, P<0.001). No significant differences existed in the percentage of each coronary risk factor between patients with and without SAT after PCI (63% vs 47% for diabetes mellitus, P=0.054, 66% vs 75% for hypertension, P=0.209, 46% vs 57% for hyperlipidemia, P=0.190, and 34% vs 28% for smoking habits, P=0.381).

Conclusions:
In patients after PCI, despite single or double antiplatelet drug therapy, the whole blood platelet aggregation should be checked, and if PATI is <6.435 the indication for additional antiplatelet therapy should be considered.
Abstract 14864: Impact of Lifestyle and Cardiometabolic Risk Factors on Atherosclerotic Cardiovascular Diseases Incidence Across Body Weight Categories: A Prospective Study of 321,259 UK Biobank Participants
Authors: Paulin Audrey , Manikpurage Hasanga D , Despres Jean-Pierre , Theriault Sebastien , Arsenault Benoit
Published: June 2023

Introduction:
Individuals with an elevated body mass index (BMI) are at higher atherosclerotic cardiovascular diseases (ASCVD) risk. While the impact of an elevated BMI on ASCVD risk in individuals who are “metabolically healthy” is still debated, the respective contributions of BMI and actionable lifestyle and cardiometabolic risk factors on ASCVD risk remains largely unknown. We investigated the respective contributions of lifestyle and cardiometabolic risk factors and BMI to ASCVD incidence in apparently healthy individuals.

Methods:
We developed a cardiovascular health score (CVHS) based on three lifestyle (smoking status, fruits and vegetables consumption and physical activity levels) and six cardiometabolic (blood pressure, HbA1c, LDL-C, HDL-C, C-Reactive Protein and triglyceride levels) parameters. The study sample included 321,259 participants of the UK Biobank, free of ASCVD recruited between 2006 and 2010. As of August 2021, 15,699 of them had incident ASCVD (fatal or nonfatal myocardial infarction, ischemic stroke or cardiac revascularization procedures. The impact of the CVHS on incident ASCVD alone and in BMI categories was assessed using Cox proportional hazards adjusted for age, sex, ethnicity and deprivation.

Results:
Compared to participants with a very high CVHS (CVHS=9), those with a very low CVHS (CVHS=0) had a higher ASCVD risk (hazard ratio = 12.2 (95% CI, 6.7-22.2, p<0.001). Figure 1 presents the association between the CVHS and hazard ratio for incident ASCVD in four BMI categories.

Conclusions:
In participants of the UK Biobank, a cardiovascular health score based on lifestyle and cardiometabolic risk factors was strongly associated with incident ASCVD in all BMI categories. The relationship between BMI and ASCVD incidence across CVHS categories was inconsistent. Strategies aimed at improving healthy lifestyle habits and cardiometabolic risk factors may decrease ASCVD risk in everyone, regardless of their body weight.
Abstract 14868: Identification of Novel Small Molecule Inhibitors of Calcium/Calmodulin-Dependent Protein Kinase II Delta for Treatment of Beta-Blocker Resistant Arrhythmia
Authors: Schulman Howard , Paraselli Bheema , Pellicena Patricia , Levy Daniel E
Published: June 2023

Introduction.
CaMKIId is a validated drug target in atrial fibrillation (AF), ventricular arrhythmia, and HF. As a key mediator of Ca
2+
action, it is hyperactivated by dysregulated Ca
2+
homeostasis with pathological consequences, which can be normalized by a variety of genetic and pharmacological manipulations.

Objectives.
Develop an ATP competitive CaMKIId inhibitor with nanomolar potency for initial efficacy in an AF mouse model and further optimization of selectivity, PK and low CNS penetration.

Methods and Results.
Molecular modeling using the crystal structure of human CaMKIId with several scaffolds as a starting point, led to development of a consistent structure activity relationship model and design of AS283. The molecule is an ATP competitive inhibitor with an IC
50
of 6nM and Ki of 1nM. Unlike KN-93, a common tool inhibitor of CaMKII in preclinical studies, AS283 inhibits the autophosphorylated, Ca
2+
-independent form of the kinase. AS283 shows preclinical proof of concept in both ventricular arrhythmia and AF models, with the latter described here. Mice with a gain of function mutation in the RyR2 receptor (R
178Q/+
) do not undergo spontaneous AF but have an increased vulnerability to AF in response to atrial pacing. Intracardial electrophysiology with recording of atrial and ventricular electrograms (Na Li and Xander Wehrens, Baylor College) were used to select mutant and wild-type mice that exhibited AF in pacing trials. AF-positive animals were randomly assigned to treatment with placebo or AS283, with KN-93 as control. AS283 completely suppressed incidence of AF in comparison to placebo and exhibited a dose response. Autophosphorylation of CaMKIId at Thr287 was used as a biomarker of target engagement. As anticipated, atrial pacing increases intracellular Ca
2+
leading to activation of CaMKII and increased P-Thr287. AS283 blocked the increase in P-Thr287.

Conclusion.
AS283 is a novel, potent CaMKIId inhibitor with robust preclinical efficacy, supporting its further optimization for PK and low CNS penetration. Consistent with studies using genetic and pharmacological tools, an optimized, small molecule inhibitor of CaMKII has a promise in treating arrhythmias that are sub-optimally managed with or contraindicated to beta blockers.