bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10017: Which Thrombi at the Apex of the Left Ventricle Were More Prone for Embolization and Stroke?
Authors: Nguyen Thach N , Hsu Che Wei , PHAM THIEN , Nguyen Cardy , Nguyen Nga , Le Ha , Hoang Mai Q , Le Trang , Ha Quang Dat , Vu LOC , Vu Quang Phuc , Huynh Duong , Aggarwal Sarthak , Le Thoa , Mihas Imran
Published: June 2023

Introduction:
Patients with apical thrombus due to anterior wall ST segment Elevation Myocardial Infarction (AWMI) or dilated cardiomyopathy (DilCM) have high risk of emboli, including stroke.

Hypothesis:
Which factor of a thrombus at the apex of the left ventricle makes it vulnerable for or resistant to embolization? Is it its loose (or well organized) tissue formation as a fresh (or old) thrombus so it disintegrates quickly (or stays resistant) and becomes vulnerable for (or less prone to) embolization?

Methods:
Patients with AWMI or DilCM with apical thrombus by echo were consecutively enrolled. Patients with atrial fibrillation were excluded. The data to be collected included: (1) Time of discovery of apical thrombi by echo to time of stroke (2) result of treatment (thrombolysis with long term vit K antagonists vs novel oral anticoagulants (NOACs) and (3) pattern of recovery.

Results:
From 2010-2021, there were 32 patients identified with apical thrombus. 12 patients due to AWMI and 20 patients due to Dil CM. 3 AWMI patients developed stroke (25%) within a mean of 7.5 days after discovery while only 2 patients with Dil CM had stroke (10%) 21 days after discovery (p<0.05). At the time of stroke, all apical thrombi of AWMI patients were small, of round shape, protruding out and of heterogenous consistency (mixed black and white intensity on echo). The patients responded well to thrombolysis and recovered near completely. While for patients with Dil CM, all apical thrombi were moderately large, of flat surface incorporating into the contour of the apex, non-protruding and of homogenous consistency. When these patients had stroke, the size of stroke was large and more resistant to thrombolysis. Their recovery was slow with a lot of deficits.

Conclusions:
For apical thrombi from AWMI, the thrombi were fresh so they disintegrated quickly and could cause more stroke however because of their smaller size and loose consistency, the recovery was more complete. The apical thrombi from Dil CM were more organized so they dissolved more slowly, caused less stroke however they were more resistant to thrombolysis. Their recovery was more limited. Larger database needs to confirm the above findings and their clinical implications.
Abstract 10040: Impact of Periaortic Adipose Tissue Detected by Computed Tomography on Aortic Vulnerable Plaques Identified by Non-Obstructive General Angioscopy
Authors: Koyama Yutaka , Kojima Keisuke , Takahashi Kurara , Migita Shohei , Miyagawa Masatsugu , Tanaka Yudai , Fujito Hidesato , Ohgaku Akihito , Ebuchi Yasunari , Arai Riku , Monden Masaki , Fukumoto Katsufumi , Takei Norio , Murata Nobuhiro , Fukamachi Daisuke , Okumura Yasuo
Published: June 2023

Introduction:
Periaortic adipose tissue (PAAT) is related to the development of cardiovascular disease. However, the relationship between periaortic adipose tissue (PAAT) and aortic plaque instability has not been elucidated.
Hypothesis:
We hypothesized that PAAT would be associated with aortic vulnerable plaques derived non-obstructive general angioscopy (NOGA) in patients with cardiovascular disease.

Methods:
We investigated 117 patients who underwent NOGA of the aorta and CT. PAAT volume was measured using the volume-rendering method by extracting the area from -30 to -190 HU within the thoracic aorta. PAAT volume index (PAAT-I) was defined as PAAT volume divided by the body surface area. We evaluated the number of vulnerable plaques including ruptured plaques, ulcerations, thrombi, intense yellow plaques by NOGA in the whole aorta. All patients were divided into the median value of PAAT-I (16.9 [13.0 - 21.6] ml/m2)

Results:
The high PAAT-I patients had significantly greater number of vulnerable plaques in the thoracic aorta than the low PAAT-I patients (2 [1-4] vs 1 [0-3], p<0.05). The PAAT-I had a correlation with the number of vulnerable plaques in the thoracic and whole aorta (r=0.44, p<0.001, r=0.35, p<0.01, respectively)

Conclusions:
PAAT in the thoracic aorta was related to the number of NOGA derived-aortic vulnerable plaques in patients with cardiovascular disease. PAAT may play an important role in the development of aortic plaque instability.
Abstract 10063: Changes in Clinical Phenotype of Patients With ATTR Cardiac Amyloidosis During the Past 20 Years
Authors: Ioannou Adam , Patel Rishi , Razvi Yousuf , Porcari Aldostefano , Venneri Lucia , Masi Ambra , Massa Paolo , Knight Daniel , Martinez-Naharro Ana , Kotecha Tushar , Chacko Liza , Lachmann Helen , Wechalekar Ashutosh , Whelan Carol , Hawkins Philip , Gillmore Julian D , Fontana Marianna
Published: June 2023

Introduction:
Diagnostic and therapeutic advances have led to increased awareness of transthyretin cardiac amyloidosis (ATTR-CA). We sought to characterise the change in clinical phenotype of patients with ATTR-CA over the last 20-years.

Methods:
We studied 1967 patients diagnosed with ATTR-CA at the National Amyloidosis Centre (NAC) from 2002-2021.

Results:
Analysis by 5-year quartiles revealed a substantial incremental increase in patients diagnosed, with the most marked increases seen in wild-type ATTR. Increased diagnoses were accompanied by greater proportions of patients referred following bone scintigraphy and cardiac magnetic resonance imaging (3% vs 44% vs 67% vs 76%, P<0.001). Over time, median duration of symptoms prior to diagnosis diminished from 36-months between 2002-2006 to 12-months between 2017-2021 (P<0.001) and a greater proportion of patients had milder disease at the time of diagnosis across the 5-yearly quartiles (NAC stage 1: 34% vs 42% vs 44% vs 53%, P<0.001). The latter was associated with more favourable echocardiographic parameters of structure and function, including an incremental decrease in interventricular septal thickness(18.0±3.8mm vs 17.2±2.6mm vs 16.9±2.3mm vs 16.6±2.4mm, P=0.01), which was associated with improved survival. The improved survival associated with the year of diagnosis remained significant when censoring at trial or disease modifying medication start date (2012-2016 vs. 2017-2021: HR=1.05, 95%CI[1.03-1.07], P<0.001).

Conclusions:
Increased awareness and advances in cardiac imaging have been associated with a substantial increase in diagnosis of ATTR-CA and at a progressively earlier stage of the disease, which has contributed to improved survival in recent years. These changes may have important implications for initiation and outcome of therapy and urgently need to be factored into clinical trial design.
Abstract 10075: Hematopoietic Mosaic Chromosomal Alterations and Cardiovascular Disease-Related Deaths Among Cancer Survivors: An Analysis of the UK Biobank
Authors: Sun Maxine , Cyr Marie-Christyne , Sandoval Johanna , Lemieux Perreault Louis-Philippe , Busque Lambert , Tardif Jean-Claude , Dube Marie-Pierre
Published: June 2023

Introduction:
Cancer survivors are at an increased risk for cardiovascular (CV)-related deaths. Recently, clonal hematopoiesis (CH) was described as a novel risk factor for both cancer and CV disease. However, the influence of CH on CV outcomes in cancer survivors has not been explored.

Hypothesis:
We hypothesized that CH captured by mosaic chromosomal alterations (mCA) could predict the risk of CV outcomes and death following cancer diagnosis.

Methods:
In the UK Biobank, we identified patients with a history of selected cancer types known for their high CV risk. mCAs were detected using DNA genotyping array intensity data. The association of mCA with CV-death, coronary artery disease (CAD)-death, and any cause death was performed using Cox proportional hazards regression, adjusting for age, sex, smoking, chemotherapy, radiotherapy, and ancestry. Exploratory analyses also included incident CV phenotypes. The specificity of the effect was assessed using a model with an interaction term between mCA and cancer history.

Results:
Among 48 919 unrelated individuals with a cancer diagnosis, 10 070 patients (20.6%) carried ≥1 mCA clone. Of those, 2432 were autosomal carriers and 1910 had a mCA in ≥10% of peripheral leukocytes. mCA prevalence increased with age: from 4.8% among those aged <49 years old to 30.4% for those aged ≥70 years old. mCA was associated with an increased risk of CAD-death (HR 1.37, 95% CI 1.09-1.71,
P=
0.006) and overall mortality (HR 1.07, 95% CI 1.02-1.11,
P
=0.006). In exploratory analyses, mCA was associated with higher risks of incident STEMI (HR 1.18, 95% CI 1.02-1.37,
P
=0.022) and peripheral vascular disease (HR 1.17, 95% CI 1.04-1.31,
P
=0.007). The effect of mCA was specific to cancer survivors for any cause of death (
P
interaction
<0.001) but not for CAD-death (
P
interaction
=0.96).

Conclusions:
Our findings indicate that among cancer survivors, CH captured by mCA was associated with a higher risk of CAD death and overall mortality. Cancer survivors with CH may benefit from targeted CV screening and preventive measures to better manage individual CV risk.
Abstract 10085: Troponin Release is Associated With Mortality and Poor Fluid Resuscitation in Patients With Sepsis
Authors: Ma Zhiyuan , Krishnamurthy Mahesh , Modi Vivek , Allen David , Shirani Jamshid
Published: June 2023

Introduction:
Septic patients are predisposed to myocardial injury manifested as cardiac troponin release (TnR). Prognostic significance and management implications of TnR in this setting has not been fully elucidated. We aimed to determine the impact of admission TnR and fluid resuscitation on outcomes of patients with sepsis admitted to intensive care units (ICU).

Methods:
A total of 24,778 patients with sepsis from eICU-CRD (n=11,992), MIMIC-III (n=6,638) and MIMIC-IV (n=6,148) databases were examined for mortality and 1-year survival by multivariable logistic, Cox regression analysis, or Kaplan-Meier survival analysis with overlap weighting adjustment, as well as generalized additive models for fluid resuscitation.

Results:
TnR on admission was associated with higher in-hospital mortality [adjusted odds ratios (aOR)=1.33; 95% confidence interval (CI)=1.23-1.43; p< 0.001 in unweighted analysis and aOR=1.39; 95% CI=1.29-1.50; p< 0.001 with overlap weighting]. One-year survival was lower in patients with admission TnR (Kaplan-Meier survival analysis; p=0.002). A trend was noted for association between admission TnR and 1-year mortality [aOR=1.16; 95% CI, 0.99-1.37; p = 0.067 in unweighted analysis] while the association was statistically significant after overlap weighting (aOR=1.25; 95% CI=1.06-1.47; p=0.008). We also found that patients with admission TnR were less likely to benefit from more liberal fluid resuscitation. Adequate fluid resuscitation within a range of 70 to 90 ml/kg in the first 24 hours of ICU stay was associated with lower in-hospital mortality in septic patients without TnR but not in those with admission TnR.

Conclusions:
Admission TnR was significantly associated with higher in-hospital mortality and worse 1-year survival among septic patients. Adequate fluid resuscitation improved in-hospital mortality in septic patients without but not with admission TnR.
Abstract 10090: Computed Tomography is Non-Inferior to Cardiac Angiography in Differentiating Dual- versus Single- Supply Major Aortopulmonary Collaterals Among Patients With Pulmonary Atresia or Critical Stenosis
Authors: Shalhoub Khayri , Prakash Ashwin , Ali Mohsin , Gauvreau Kimberlee , Ghelani Sunil J , Maschietto Nicola
Published: June 2023

Introduction:
Anatomic characterization of pulmonary blood flow is of paramount importance in patients with major aortopulmonary collaterals (MAPCAs). Although computed tomography angiography (CTA) is an appealing alternative to cardiac angiography (CA), its ability to differentiate between single- versus dual-supply MAPCAs is not well-established. We investigated whether CTA is non-inferior to CA in defining MAPCAs supply.

Methods:
Retrospective analysis of patients who underwent both CTA and CA for MAPCA delineation between 2016-2021. Diagrams were created for patients labeling MAPCAs numerically for consistency in data collection. Images were independently reviewed by blinded CTA and CA readers. The diagnostic performance of CTA was compared to CA as the gold standard. Nonparametric paired tests were used for statistical analysis, and 95% confidence intervals were calculated using exact methods.

Results:
Seventeen patients, with 55 MAPCAs, met the study criteria. The median age at CTA and CA was 7 days (1-745) and 74 days (7-751), respectively. CA was performed under general anesthesia (GA) in all patients compared to 17% of CTAs (p=0.0001). Contrast load (median 2 vs 7.1 ml/kg) and adverse events (0 vs 47%) were lower in CTA than diagnostic CA (p <0.0001 and p.=0.008, respectively). Fifty-three MAPCAs (96%) were concordantly classified as single or dual supply (95% CI, 87-100%). Compared to CA, CTA detected dual-supply MAPCAs with sensitivity of 97% (95% CI, 84-100%) and specificity of 96% (77-100%); similarly, PPV was 97% (84-100%) and NPV was 96% (77-100%). The proportion of MAPCAs labeled discordantly was non-inferior at both the 10% margin (p=0.0001) and 5% margin (p=0.031).

Conclusions:
CTA is accurate in differentiating single- versus dual-supply of MAPCAs. Additionally, CTA required a lower contrast load, less frequent use of GA, and resulted in fewer adverse events. Our results suggest that CTA may be used as the initial diagnostic modality for complete MAPCAs delineation, with CA reserved when an intervention or hemodynamic assessment is necessary.
Abstract 10142: Stratification of the Risk of Developing Heart Failure in Patients With Left Bundle Branch Block: Approach Using Artificial Intelligence
Authors: Yagi Ryuichiro , Goto Shinichi , Macrae Calum A , Deo Rahul C
Published: June 2023

Introduction:
Left Bundle Branch Block (LBBB) is a common ECG abnormality associated with impaired ventricular function. However, large individual variation in heart failure (HF) risk in patients with LBBB has been observed.

Hypothesis:
Subtle phenotypic changes reflecting cardiac dysfunction are present on ECG and are detectable using artificial intelligence (AI).

Methods:
All 12-lead ECGs with LBBB recorded from 1/1/2015 to 12/31/2019 were identified in our institution, and analyzed as a matrix of the dimension of 12 (representing twelve leads) x 2500 (representing 250Hz x 10 seconds). A 2-dimensional convolutional neural network was trained to detect ECG features related to HF. The model was then applied to an external cohort of patients with LBBB but without history of known HF. Cumulative incidences of HF admission were compared by stratifying according to tertiles of the model output (low, intermediate and high AI score groups) using Kaplan-Meier curves, log-rank test, and Cox proportional hazard model.

Results:
The test cohort consisted of 2,664 individuals with LBBB and 490 (18.4%) were admitted for HF during median follow-up of 1,091 days (IQR 209-1,666). While 12.6% in the low score group experienced HF hospitalization, 18.0% in the intermediate score group and 24.5% in the high score group were admitted due to HF (high vs low AI score group: hazard ratio (HR) 2.11 [95%CI 1.68-2.65]; intermediate vs low AI score group: HR 1.44 [95%CI 1.13-1.83]; log rank p <0.0001;
Figure
). The association between AI score and HF admission was significant after adjusting for patient characteristics and conventional ECG parameters (high vs low AI score group: adjusted HR 1.94 [95%CI 1.52-2.47], p<0.0001; intermediate vs low AI score group: HR 1.34 [95%CI 1.05-1.72], p=0.02), and in a subpopulation with at least 2-years of follow-up (log rank p=0.002).

Conclusions:
The AI model exhibited excellent discrimination for HF admission risk in patients with LBBB.
Abstract 10151: Detection of Cardiac Involvement in Eosinophilic Granulomatosis With Polyangiitis (EGPA) With Multiparametric Cardiovascular Magnetic Resonance (CMR)
Authors: Hua Alina X , Sularz Agata , Dhariwal Jaideep , Nanzer Alexandra , Jackson David , Ismail Tevfik F
Published: June 2023

Background:
EGPA is a rare small-vessel vasculitis. Cardiovascular (CV) involvement is an important predictor of adverse outcomes but is challenging to detect. CMR is as an excellent tool to detect cardiac EGPA but is not widely available. It is unknown who would benefit most from comprehensive CV assessment with CMR. We aimed to determine the prevalence of cardiac EGPA with multiparametric CMR and to identify potential clinical/biochemical predictors of CV involvement.

Methods:
This single-center study was performed in EGPA patients who underwent CMR as part of routine clinical evaluation including comprehensive tissue characterization with T1 mapping, T2-STIR, T2 mapping, and late gadolinium enhancement imaging, in accordance with SCMR guidelines.

Results:
Sixty-three EGPA patients were included (Table 1). CV involvement (defined by typical LGE, LV dysfunction or pericardial inflammation) was seen in 37%. The median LV and RV ejection fraction was 58% and 57%. Two (3%) patients demonstrated increased T2 signal and mapping values, suggesting acute cardiac injury. LGE was present in 18 (29%) patients with a predominant pattern of subendocardial fibrosis. Patients with CV involvement were younger when diagnosed with EGPA, had higher NT-pro-BNP level (sensitivity 30%, specificity 98%) and lower EF (sensitivity 48%, specificity 100%) (Table 1). Troponin levels were not predictive of CV involvement (Table 1) as defined by positive CMR.

Conclusion:
Clinical and biochemical markers had low sensitivity for detecting cardiac involvement which was present in over a third of patients. CMR is necessary to detect cardiac involvement and should be considered part of the baseline evaluation of patients with EGPA.
Abstract 10177: Pacing-Induced Cardiomyopathy: A Systematic Review and Meta-Analysis of Definition, Incidence, Risk Factors and Management
Authors: Somma Vincenzo , Ha Francis J , Palmer Sonny , Mohamed Uwais , Agarwal Sharad
Published: June 2023

Introduction:
Pacing-induced cardiomyopathy (PiCM) is a potential adverse sequela of right ventricular pacing. Definition varies between studies and the optimal management approach is uncertain. We aimed to characterize definition, incidence, risk factors and treatment strategies of PiCM.

Methods:
We performed a systematic review and meta-analysis of human studies that evaluated PiCM following pacemaker implantation identified through a literature search of PubMed and EMBASE up to March 2022. Included studies had fifty or more participants. We collected data regarding study definition of PiCM and calculated pooled prevalence across studies. Meta-analysis with random-effects modelling was used to assess association between risk factors and PiCM, reported as odds ratio (OR) with 95% confidence interval (CI).

Results:
Twenty-six studies (six prospective studies) with a total of 57993 patients (mean/median age 51-78 years, female 45%) were included in final analysis. Fifteen unique definitions of PiCM were reported; the most common definition was left ventricular ejection fraction (LVEF) <50% and LVEF decline ≥10% after pacemaker insertion. Pooled prevalence of PiCM was 12% (95%CI, 11-14%; Figure 1). On meta-analyses, risk factors included male sex (OR 1.23 95%CI 1.12-1.35), baseline LVEF (OR 0.95 per 1% increase, 95%CI 0.93-0.97), paced QRS complex duration (OR 1.02 per msec, 95%CI 1.01-1.03) and right ventricular pacing (RVP) burden (OR 1.02 per 1% increase, 95%CI 1.01-1.02). Treatment strategies identified included cardiac resynchronisation therapy (five studies) and his bundle pacing (three studies).

Conclusions:
Definition of PiCM varied significantly between studies. More than one in ten patients with a pacemaker with RV pacing developed PiCM. Risk factors included male sex, baseline LVEF, paced QRS duration and RVP. The optimal management strategy is not yet established. Further research is needed to define and treat this understated complication.
Abstract 10242: Right Atrial Function and Fibrosis in Relation to Successful Atrial Fibrillation Ablation
Authors: Hopman Luuk H , Visch Julia , Bhagirath Pranav , van der Laan Anja , Mulder Mark , Razeghi Orod , Kemme Michiel , Niederer Steven A , Allaart Cornelis , gotte marco J
Published: June 2023

Introduction:
Atrial remodeling, characterized by changes in atrial structure and function, is central to the development and maintenance of atrial fibrillation (AF). Besides left atrial (LA) remodeling, right atrial (RA) remodeling may also contribute to AF perpetuation, and its presence may affect clinical outcome of AF ablation. Bi-atrial remodeling in patients with AF is rarely assessed and data on the presence of RA fibrosis, the relationship between RA and LA fibrosis, and possible association of RA remodeling with AF recurrence after ablation is limited.

Methods:
110 AF patients undergoing initial pulmonary vein isolation (PVI) were included in the present study. Patients were in sinus rhythm during cardiac magnetic resonance (CMR) imaging performed prior to ablation. LA and RA volumes and function (volumetric and strain) were derived from cine CMR images. The extent of LA and RA fibrosis was assessed from 3D late gadolinium enhancement images. AF recurrence was followed-up for 12 months after PVI using either 12 lead ECGs or Holter monitoring.

Results:
Arrhythmia recurrence was observed in 39 patients (36%) after the 90-day blanking period, occurring at a median of 181 (IQR: 122-286) days. RA remodeling parameters were not significantly different between patients with AF recurrence as compared to patients without AF recurrence after ablation, whereas LA remodeling parameters were (volume, emptying fraction and strain). LA fibrosis had a strong correlation with RA fibrosis (r=0.88,
P
<0.001). Both, LA and RA fibrosis was not different between patients with and without AF recurrence.

Conclusions:
RA remodeling parameters were not predictive of AF recurrence after AF ablation. Bi-atrial fibrotic remodeling is present in AF patients and the amount of LA fibrosis had a strong correlation with the amount of RA fibrosis. The presence of bi-atrial fibrotic tissue may be an expression of disease state although no relation with AF recurrence after AF ablation was found.
Abstract 10265: Association of Myocardial Mechanical Markers of Extracellular Volume Expansion With Heart Failure and All-Cause Mortality: The Multi-Ethnic Study of Atherosclerosis
Authors: Varadarajan Vinithra , Dorbala Sharmila , Watson Karol E , Nguyen Hieu , Ambale Venkatesh Bharath , Ac Lima Joao A , Shea Steven , Post Wendy S , McClelland Robyn , Wu Collin
Published: June 2023

Introduction:
Characteristic myocardial deformation indices have been proposed to be associated with extracellular volume (ECV) expansion and differentiate cardiac pathologies that induce cardiac remodeling.

Hypothesis:
Our hypothesis was that such mechanical markers are associated with (1) pathologic ECV expansion and cardiac remodeling and (2) clinical outcomes of heart failure and mortality.

Methods:
Our analysis included 2778 participants who underwent cardiac MRI at the Multi-Ethnic Study of Atherosclerosis Exam 5 (2010-2012). The following deformation indices were calculated: relative apical strain ratio (RAS), septal apical basal ratio (SAB) and ejection fraction circumferential strain ratios (EFSR). We used linear regression to analyze the associations of these deformation indices with cardiac remodeling and ECV expansion. We used Cox proportional models to investigate the associations of mechanical deformation indices with incident HF and all-cause mortality.

Results:
The mean (SD) age of the cohort at Exam 5 was 69.1 (9.3) years; 53% were female. MRI tagging and T1 mapping analyses showed that higher levels of EFSR were associated with 0.2% greater ECV and 4.4ms higher native T1. In addition, EFSR was associated with 3.59ml lower LV end-diastolic volume, 1.98g higher LV mass and 0.13
⃘
higher torsion. EFSR was associated with greater LA volume, decreased total emptying fraction and reduced maximal strain (Table 1). During a follow-up period of 7.5 years (Figure 1), there were 101 incident heart failure events, and 228 all-cause deaths. In the multivariable cox regression analysis, hazard ratios (95% CI) of incident HF and all-cause mortality for each unit increase of EFSR were 1.36 (1.04,1.78) and 1.31 (1.05,1.64) (Table 2), respectively.

Conclusion:
Mechanical markers of extracellular expansion are associated with adverse cardiac remodeling, incident HF and all-cause mortality.
Abstract 10279: Three-Dimensional Deep-Tissue Imaging of the Right Ventricle Reveals the Complex Remodeling of the Microvascular Network in Right Heart Failure
Authors: Ichimura Kenzo , Boehm Mario , Andruska Adam , Schimmel Katharina , Zhang Fan , Bonham Spencer , Kabiti Angela , Kheyfets Vitaly O , Reddy Sushma , Wang Gordon , MacArthur John , Woo Y. Joseph , Metzger Ross , Spiekerkoetter Edda F
Published: June 2023

Introduction:
Right ventricular (RV) failure is the leading cause of death in patients with pulmonary arterial hypertension (PAH). Capillary rarefaction has been proposed as the hallmark of RV failure, yet our understanding of the capillary architecture is limited by 2D image analysis. Three-dimensional (3D) confocal deep tissue imaging offers the unparalleled opportunity to characterize the architectural microvascular changes in relationship to cardiomyocytes in pressure-overloaded RV failure.

Methods and Results:
250 μm heart tissue slices from mice with RV failure, 7-weeks after Pulmonary Artery Banding (PAB) were harvested and the microvascular network was assessed for density, segment length, diameter, orientation, as well as microvasculature-cardiomyocyte contact area in regions with and without interstitial fibrosis using confocal 3D imaging. Human heart tissue from end-stage PAH patients was compared to controls with normal RV function. In PAB mice, 3D imaging of the RV free wall revealed tortuous, shorter, thicker and higher-branched microvascular segments as well as development of fibrosis compared to Sham animals (Fig A). When corrected for fibrosis, the microvascular density was preserved even in advanced stages of RV failure. Physical contact between the microvasculature and cardiomyocytes was preserved in areas without fibrosis, yet significantly impaired in areas with interstitial fibrosis (Fig B), accompanied by an overexpression of β-myosin heavy chain suggesting local ischemia (Fig C). 3D imaging of human RV tissue of end-stage PAH patients revealed architectural microvascular remodeling that varied depending on etiologies and length of disease yet showed preserved microvascular density. (Fig. D).

Conclusions:
3D deep tissue imaging revealed compensatory changes of the microvascular network to maintain a stable cardiomyocyte coverage in pressure-overloaded RV failure, which was impaired in areas of interstitial fibrosis.
Abstract 10305: A Bioresorbable Pacemaker With Transient Closed-Loop System
Authors: Choi Yeonsik , Yin Rose , Pfenniger Anna , Arora Rishi , Efimov Igor , Rogers John A
Published: June 2023

Introduction:
Conventional temporary pacemakers with percutaneous pacing leads limit patient mobility, create risks for infections, require removal procedures following completion of therapy and demand an additional collection of wired devices to monitor the status of the patient and to provide closed-loop operation. Recently reported wireless, bioresorbable pacemakers avoid the first set of disadvantages, but they must still be paired with conventional wired-based systems for cardiac monitoring, power delivery and control.

Methods:
We present a bioresorbable pacemaker that combines with a wirelessly networked collection of temporary, body-integrated devices to (1) power, control, and monitor processes of cardiac stimulation, (2) track cardiopulmonary status via comprehensive, multi-modal measurements, (3) provide patient-specific multi-haptic feedback on device and physiological status, and (4) support transient operation through bioresorption and gentle removal from the skin.

Results:
Data captured from various locations of the body yield detailed information of patient status, across various aspects of cardiopulmonary health and physical activity. The results define autonomous rate-adaptive pacing parameters to match metabolic demand via wireless powering of the bioresorbable module. Operation is possible over extended periods to match clinical needs, enabled by advanced mechanical designs and drug eluting configurations of the battery-free, bioresorbable pacemaker platform. Replacement of the cardiac module can occur in a manner that does not disrupt continuous pacing. The skin-interfaced devices can be easily peeled away for removal after patient recovery, due to their soft, flexible construction.

Conclusions:
We demonstrate for the first time that a bioresorbable pacemaker with transient closed-loop system is feasible in a clinically relevant, large animal and human whole heart model. Further improvements in this technology could open doors for out of hospital temporary pacing for varying periods of time, without the need for permanent hardware.
Abstract 10378: Metabolomic Signatures of Myocardial Glucose Uptake on FDG-PET
Authors: Vidula Mahesh K , Kelly Daniel P , Arany Zoltan , Margulies Kenneth B , Shah Svati H , Petucci Chris , Cappola Tom , Bravo Paco E , Selvaraj Senthil
Published: June 2023

Introduction:
FDG-PET is critical for evaluating myocardial inflammation, but requires preparation with a ketogenic diet (KD) to suppress physiologic myocardial glucose uptake (MGU). Even in monitored settings, incomplete suppression occurs in ~20% and remains the Achilles’ heel of the KD technique. We recently found in a crossover trial (NCT04275453; KEETO-CROSS) that despite achieving robust ketosis, ketone ester (KE) drink was inferior to KD to suppress MGU. We sought to understand whether a common metabolite signature might predict myocardial glucose suppression (MGS) irrespective of technique to ensure adequate myocardial preparation.

Methods:
Twenty healthy participants were first randomly assigned to acute KE ingestion or KD (24/72 hour visits) with subsequent crossover. Targeted plasma metabolomic profiling of 61 metabolites was performed at these 3 visits paired with FDG-PET. The association between metabolites and MGU was assessed using mixed effects linear regression.

Results:
The mean age of the participants was 30±7 years (50% women and 45% non-white). The
Figure
shows volcano plots for the relationship between metabolites and MGU. In both arms, two C4-OH carnitine species (markers of ketone/fatty acid oxidation) were strongly and inversely associated with MGU. Both species (C4-OH isobutyrylcarnitine and C4-OH butyrylcarnitine) were predictive of MGS in all patients (c-statistic 0.83, 95% CI 0.65-1.00 and 0.81, 95% CI 0.70-0.92, respectively) and much stronger than ketone/fatty acid levels. C4-OH isobutyrylcarnitine levels were higher during 24/72 hour KD visits than KE (p=0.018 and p=0.003).

Conclusions:
Metabolite markers of ketone and fatty acid oxidation strongly predict MGS, have robust discriminatory value, and may be used upstream of FDG-PET to reduce false positive scans. Strategies to enhance ketone/fatty acid oxidation (rather than circulating ketone/fatty acid levels) may improve MGS.
Abstract 10388: Impact Of Right Ventricular Function On Cardiopulmonary Exercise Capacity In Mitral Regurgitation Patients Undergoing Transcatheter Mitral Valve Repair
Authors: Gercek Muhammed , Ivannikova Maria , Gerçek Mustafa , Goncharov Arseniy , Friedrichs Kai P , Rudolph Volker , Dumitrescu Daniel
Published: June 2023

Background/Objectives:
To investigate the role of right ventricular (RV) function on exercise capacity in patients undergoing transcatheter mitral valve repair (TMVR) we aimed to perform cardiopulmonary exercise testing (CPET) and to show a correlation between an improved RV function and maximal and submaximal exercise capacity.

Methods:
Constant work rate exercise time testing (CWRET) reflects submaximal/endurance exercise capacity, which is more likely to be relevant for daily life activities, and gives a more differentiated physiologic insight into the nature of exercise intolerance. Thus, 28 Patients with mitral regurgitation (MR) and symptomatic heart failure (NYHA≥II) underwent CPET by assessment of maximal oxygen uptake (peak VO
2
) and submaximal exercise capacity (at 75% of maximal achieved work rate in the initial incremental exercise test) accompanied by echocardiography prior to TMVR and 3 months post-procedure.

Results:
Mean age of the patients was 75.0±8.7 years and 32.1% of them were female. One patient presented a reduction of MR <2 grades. RV function (assessed with fractional area change, tricuspid annular plane systolic excursion, longitudinal strain of the RV free wall and S`) was at least moderately impaired in 25% of the patients. The submaximal exercise capacity of these patients was impaired, but did not significantly differ (416.4±359.6sec vs. 296.1 ±216.5sec; p=0.152) compared to patients without a deteriorated RV function. Three months after intervention, exercise time at 75% of maximal achieved work rate significantly improved (from 337.4±262.2sec to 517.4±393. sec p=0.006), reflecting a gain in submaximal exercise tolerance. peak VO
2
showed a positive trend, but no statistically significant difference (10.3±3.1ml/min/kg vs. 11.3±3.4ml/min/kg; p=0.056). RV function (at least 2 of 4 parameters) improved in 35.7% and these patients showed a significantly higher submaximal exercise time increasement (471.7±153.9sec vs. 82.7±47.0sec, p=0.003).

Discussion/Conclusions:
TMVR may have a beneficial effect on RV remodeling. Furthermore, submaximal exercise capacity is significantly increased, reflecting an improvement especially regarding daily life activities in MR patients and impaired RV function.
Abstract 10439: Assessment of Left Atrial Deformation in Patients With Total Anomalous Pulmonary Venous Connection by Two-Dimensional Speckle-Tracking Echocardiography - A Single-Center Retrospective Cohort Study
Authors: Numata Ryusuke , Takigiku Kiyohiro , Takei Kohta , Akazawa Yohei , Obinata Haruka
Published: June 2023

Background:
Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease of newborns characterized by insufficient left ventricle growth and diastolic dysfunctions. We hypothesized that reduced blood flow into the left heart in the uterus could also affect left atrium (LA) growth, leading to anomalies after birth. We compared the age-related changes in LA parameters detected using two-dimensional speckle-tracking echocardiography (2DSTE) in patients with TAPVC.
Method:
The LA datasets of 28 neonates with isolated TAPVC were analyzed before surgery and during follow-ups and compared with those of age-matched healthy controls (January 2009–2022). The LA strain (ε), indicating LA function, was analyzed using QLAB represented by reservoir (εR), conduit (εCD), and contractile (εCT) functions. LA pressure was determined by performing catheterization.

Results:
Compared to the control group, the TAPVC group had significantly smaller LA maximum size preoperatively and normal and larger time-dependent increase in the LA maximum and minimum size, respectively. All 2DSTE-determined LA functions showed significant reductions at all time points in the TAPVC group compared to those in the control group (median εR, εCD, and εCT; before surgery: 17.0 vs. 26.0, 12.9 vs. 15.9, and 6.3 vs. 10.4; follow up at 1-2 years: 30.0 vs. 45.7, 23.2 vs. 29.6, and 6.1 vs. 16.3; follow up at 5-7 years: 31.2 vs. 43.1, 25.0 vs. 31.2, and 5.2 vs. 10.8, respectively;
p
< .01). However, compared to before surgery, εR and εCD did represent a significantly increased trend at follow-ups (median εR and εCD: 16.8→27.5 and 1.1→23%, respectively). Patients with pulmonary venous obstruction (PVO) at birth showed significantly decreased εR and εCD and higher LA pressure compared to those without PVO.

Conclusion:
This study showed that LA impairments existed even after repair in patients with TAPVC, suggesting that LA function loss mediated by less blood flow persist in childhood.
Abstract 10446: Prognostic Significance of Left Ventricular Ejection Fraction in Atrial Fibrillation Patients Without Pre-Existing Heart Failure
Authors: Hamatani Yasuhiro , Iguchi Moritake , Minami Kimihito , Ishigami Kenjiro , Ikeda Syuhei , DOI KOSUKE , Fujino Akiko , Masunaga Nobutoyo , Esato Masahiro , Tsuji Hikari , Wada Hiromichi , Hasegawa Koji , Ogawa Hisashi , Abe Mitsuru , Akao Masaharu
Published: June 2023

Introduction:
Atrial fibrillation (AF) increases the risk of heart failure (HF). However, little focus has been placed on the prevention of HF in patients with AF.

Hypothesis:
Left ventricular ejection fraction (LVEF) is an established echocardiographic parameters in patients with HF. We hypothesized that LVEF is a useful predictor for incident HF in AF patients even without HF.

Methods:
The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. After excluding patients without pre-existing HF (defined as having one of the following; prior HF hospitalization, New York Heart Association class ≥2, or LVEF <40%), we investigated 2,459 patients with the data of LVEF at enrollment. We divided the patients into 3 groups stratified by LVEF (mildly reduced LVEF [40-49%], below normal LVEF [50-59%], and normal LVEF [≥60%]), and compared the backgrounds and incidence of HF hospitalization between the groups.

Results:
Of 2,459 patients (mean age: 72.4±10.5 years, female: 917 [37%], paroxysmal AF: 1,405 [57%], and mean CHA
2
DS
2
-VASc score: 3.0±1.6), the mean LVEF was 66±8% (mildly reduced LVEF: 114 [5%], below normal LVEF: 300 [12%] and normal LVEF: 2,045 [83%], respectively). Patients with lower LVEF demonstrated lower prevalence of female and paroxysmal AF (both P<0.01). During the median follow-up period of 6.0 years, 255 patients (10%) were hospitalized for HF (annual incidence: 1.9% per person-year). Kaplan-Meier curves revealed that LVEF at enrollment could stratify the incidence of HF hospitalization in AF patients without pre-existing HF (
Figure
). Multivariable Cox regression analysis demonstrated that lower LVEF strata were independently associated with the risk of HF after adjustment by age, sex, AF type and CHA
2
DS
2
-VASc score (
Figure
).

Conclusion:
LVEF at enrollment could stratify the incidence of HF hospitalization in patients with AF, suggesting the importance of measuring LVEF in all AF patients even without HF.
Abstract 10480: Depression and Coronary Artery Disease Share Genetic Risk Factors Enriched in Inflammation and Cardiomyopathy-Associated Pathways
Authors: Singh Kritika , Miller-Fleming Tyne W , Lee Hyunjoon , Sealock Julia M , Gustavson Daniel E , Smoller Jordan W , Davis Lea
Published: June 2023

Coronary artery disease (CAD) and depression are highly prevalent (7% and 8% respectively), comorbid diseases. Approximately 40% of adults who are initially diagnosed with either CAD or depression will also develop the other condition. We have observed that the polygenic risk scores for depression were significantly associated with CAD in a large hospital population even in patients without any psychiatric diagnoses and after adjusting for known CAD risk factors. This suggests that some proportion of genes that increase susceptibility to depression act pleiotropically to increase CAD risk. To identify the genes increasing risk for both CAD and depression we performed a cross-tissue S-MultiXcan analysis on the summary statistics for CAD (CARDIoGRAMplusC4D Consortium) and depression (PGC and UK Biobank). We identified 185 genes associated with both depression and CAD, representing a three-fold enrichment of shared associations (
P
value <1.718e-43). Next we performed a pathway enrichment analysis and observed that these genes were enriched for inflammation and cardiomyopathy-associated pathways. We then used electronic health records at Vanderbilt, to test the prevalence of cardiomyopathy in patients with comorbid depression and CAD. We found that the depression-CAD cohort had a significantly increased prevalence of cardiomyopathy diagnoses ( OR = 1.27, 95%C.I. = 1.17-1.30,
P
value = 3.69 e-9) compared to patients with CAD after we controlled for Type 2 Diabetes, hypertension, smoking and median BMI. We replicated these findings across two external cohorts - All of Us and Massachusetts General Hospital health records. Using a Genomic structural equation model (GSEM), we observed that inflammatory markers white blood cell (WBC) count and platelet count explained 1% and 16% of the SNP-based genetic correlation between depression and CAD, respectively in a single factor. The mediation paths models using the summary statistics data show that WBC and platelets mediate approximately 1% and 13% of comorbidity and together explain 14.4% of the total genetic correlation between depression-CAD. These results highlight cardiomyopathy and inflammation as an important biological link in the comorbid manifestation of CAD and depression.
Abstract 10564: Angiovac for Vegetation Debulking in Right-Sided Infective Endocarditis: A Systematic Review and Meta-Analysis
Authors: Mhanna Mohammed , Beran Azizullah , Al-Abdouh Ahmad , Jabri Ahmad , Sajdeya Omar , Al-Aaraj Ahmad , Alharbi Abdulmajeed Abdullah , Khuder Sadik , Eltahawy Ehab
Published: June 2023

Objectives:
To investigate the utility of AngioVac-assisted vegetation debulking (AVD) in right sided infective endocarditis (RSIE)

Background:
AngioVac is a vacuum-based device that was approved in 2014 for the percutaneous removal of undesirable materials from the intravascular system. Although there are multiple reports on the use of the AngioVac device to aspirate right-sided heart chamber thrombi, data on its use to treat RSIE is limited.

Methods:
We performed a comprehensive literature search for studies that evaluated the utility of AVD. The primary outcomes of our study were the procedural success, defined as the ability of AngioVac to produce residual vegetation size <50% (RVS<50%) without serious procedural complications, and the clinical success, defined as composite of RVS<50%, in-hospital survival, absence of recurrent bacteremia, and valve function not requiring further intervention. The secondary outcomes included the individual components of the primary outcomes and average length of hospital stay. The pooled means and proportions of our data were analyzed using random-effects model, generic inverse variance method, and represented with 95% confidence intervals (CIs).

Results:
A total of 44 studies, including 301 patients (mean age: 44.6±18.2 years, 71.6% males) were included. Procedural success was achieved in 89.2% of patients (95% CI:82.3%-93.6%, I
2
=0%). Clinical success was achieved in 79.1% of patients (95%CI:67.9%-87.2%, I
2
=15%). Overall survival rate was 89.7% (95% CI:83.1%-93.9%%, I
2
=9%).

Conclusions:
Our meta-analysis demonstrates that AVD is a promising therapeutic option for RSIE offering a high success rate with a low complication rate across a wide range of patients.
Abstract 10579: Prevalence and Morphology of Premature Ventricular Contractions on Routine Athletic Electrocardiogram Screening
Authors: Gomez Sofia E , Perez Marco V , Wheeler Matthew , Hadley David M , Hwang Calvin , Kussman Andrea L , Kim Daniel , Froelicher Vic
Published: June 2023

Introduction:
The clinical implications of incidental premature ventricular contractions (PVCs) are poorly understood. Though controversial, athletes often receive electrocardiograms (ECGs) during pre-participation exams. The prevalence and morphologies of PVCs in this cohort have not been widely reported. Recent studies have defined benign PVC morphologic patterns in athlete populations that may guide clinical evaluations.

Methods:
Digital ECGs were obtained from 10,728 screened athletes aged 14 to 35 at school and professional team screenings in California. Captured PVCs were analyzed using simultaneous frontal and horizontal plane leads, displaying each standard ECG lead in full-length, allowing for morphologic categorization. PVCs were coded for morphology and benign status using recommended criteria outlined in Figure 1.

Results:
Twenty-six of 10,728 athletes (0.24%) had at least one PVC (Figure 1); 7 of those (27%) had bigeminy and 3 of those (12%) had trigeminy. Overall, participants were 43% female, 62% White, 12% Black, 9% Asian, and 8% Hispanic. Of those with PVCs, 50% were female, 65% were White, 23% were Black, 8% were Asian, and 4% were Hispanic. Twenty-four ECGs (92%) had PVCs with benign patterns, including 17 with right ventricular outflow tract, 5 with left anterior fascicle, and 2 with left posterior fascicle morphology. Two ECGs had non-benign PVCs with left bundle branch patterns and superior axes. Both of these athletes had normal echocardiograms and exercise testing and are being followed closely.

Conclusions:
We found a low prevalence of PVCs on routine ECG screening of young athletes, although evaluation of PVC prevalence and frequency are limited by the short duration of an ECG. Most incidental PVCs among young athletes had benign patterns. This study also demonstrates the value of digital ECG recorders to display simultaneous frontal and horizontal plane leads for the morphologic categorization of PVCs which may guide further workup.
Abstract 10589: Effects Of 3-Hydroxybutyrate on Cardiac and Mitochondrial Function During Heart Transplantation
Authors: Seefeldt Jacob , Berg Katrine , Jespersen Nichlas R , Dalsgaard Frederik F , Ryhammer Pia Katarina , Pedersen Michael , Ilkjaer Lars Bo , Hu Michiel , Erasmus Michiel E , Nielsen Roni , Bøtker Hans Erik , Eiskjaer Hans , Moeslund Niels
Published: June 2023

Introduction:
Cardiac transplantation following circulatory death (DCD) and normothermic regional perfusion (NRP) is a new strategy that allows assessment of cardiac function and therapeutical interventions before cardiac transplantation. Sodium-3-hydroxybutyric acid (3-OHB) increases cardiac output by 40% in heart failure patients and diminishes ischemia and reperfusion (IR) injury, presumably by improving mitochondrial energy metabolism.

Hypothesis:
We hypothesize that infusion with 3-OHB during NRP improves cardiac hemodynamic function after NRP and mitochondrial function after cardiac transplantation.

Methods:
Pigs ~80 kg underwent a 15-minute anoxic cardiac arrest followed by NRP on a heart-lung cardiac bypass machine. During NRP pigs received 3-OHB or Ringer Acetate infusion. We measured hemodynamic function invasively using pressure-volume catheters and mitochondrial function by high resolution respirometry.

Results:
Infusion with 3-OHB (360mg/kg/h) increased plasma levels of 3-OHB from 0.05±0.06mM to 3.95±1.13mM (P=0.006) following NRP. 3-OHB increased cardiac output by 5.18±0.97 L min
-1
(P<0.0001) driven by a 60% reduction in afterload (3-OHB vs. control: 1.4±0.2 vs. 2.2±0.7 mmHg*mL
-1
, P=0.02) and an increase in stroke volume of 36±11mL (P=0.006). Following transplantation and 3-OHB infusion, maximally coupled mitochondrial respiration returned to baseline levels corresponding to a 50% improvement compared with control (3-OHB vs. control: 135±25 vs. 78±26 ρmol O
2
*s
-1
mg
-1
, P=0.0008). The increment was associated with uncoupling of the inner mitochondrial membrane (3-OHB vs. control: 122±19 vs. 70±34 ρmol O
2
*s
-1
mg
-1
, P=0.018). Transplantation caused a shift in mitochondrial substrate efficiency measured as the respiratory control ratio, favoring 3-OHB over glucose linked substrates (3-OHB vs. glucose: 22±12 vs. 8±4, p=0.0008).

Conclusions:
Infusion with 3-OHB improved cardiac hemodynamic recovery following NRP. The improvement was driven predominantly by afterload reduction and was associated with an improvement in mitochondrial respiratory capacity.