bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17696: Perm1 Stabilizes Nrf2 via Keap1 Oxidation to Protect the Heart Against Reperfusion Injury
Authors: Huang Chun Yang , Oka Shinichi , Sadoshima Junichi
Published: December 2023

Introduction:
Reperfusion after ischemia (IR) produces reactive oxygen species (ROS) that promote myocardial injury. Nrf2 is a transcription factor that promotes transcription of antioxidant enzymes. Keap1 is a negative regulator of Nrf2. When oxidated by ROS, Keap1 releases Nrf2, leading to Nrf2 activation. Perm1 (PPARGC-1 and ESRR-induced regulator, muscle specific 1) is a scaffold or adaptor protein that maintains cellular metabolism. However, whether and how Perm1 protects the heart against IR injury via Nrf2 remains unknown.

Methods:
We used systemic Perm1 knockout (KO) mice and adeno-associated virus (AAV)-induced cardiac-specific Perm1 overexpression to investigate the pathological role of Perm1 in IR injury.

Results:
IR-induced myocardial infarction was greater in Perm1KO mice than in control mice. Consistently, infarction was smaller in mice with Perm1 overexpression (Infarction size/area at risk (AAR): AAV-GFP as a control 0.41 and AAV-Perm1 0.28*; p<0.05). Myocardial oxidative stress, evaluated via increases in dityrosine, 4HNE and GSSG/GSH, after IR was greater in Perm1KO but less in Perm1 overexpression mice. Expression of IR-induced Nrf2 target genes, such as catalase, superoxide dismutase 2, heme oxygenase 1, NADH quinone dehydrogenase 1 and thioredoxin 1, was inhibited in Perm1KO but promoted in overexpression mice. The detrimental effects observed in Perm1KO mice were normalized by ML334, an inhibitor of Keap1-Nrf2 interaction (Infarction size/AAR: Wild 0.42; Perm1KO 0.58; Wild with ML334 0.37 and Perm1KO with ML334 0.42*; p<0.05 vs. Perm1KO), suggesting that Perm1 protects the heart via Nrf2. In primary cultured rat cardiomyocytes, Perm1 was bound to Keap1 and promoted its oxidation, thereby stabilizing and activating Nrf2. Perm1-induced Nrf2 activation was verified with reporter gene assays using a consensus binding sequence of Nrf2, termed antioxidant response element. In an
in vitro
system using recombinant proteins, Perm1 directly bound to Keap1.

Conclusions:
These results suggest that Perm1 is a novel regulator of cellular redox homeostasis through Nrf2 activation via Keap1 oxidation that protects the heart against IR injury.
Abstract 17703: Sequential Validation of a Cuffless Photoplethysmography-Based Wristband for Blood Pressure Measurement: Algorithm Building to Regulatory Standard Trial
Authors: Ronner Eelko
Published: December 2023

Introduction:
Hypertension increases cardiovascular risk. Measuring reliable blood pressure (sBP and dBP for systolic and diastolic BP) is challenging. A photoplethysmography (PPG)-based wristband with a custom BP algorithm could provide continuous BP. The algorithm was made by PPG channel aggregation, band-pass filtering and segment creation and evaluated the different PPG colors. Noise and interference were removed. PPG segments were created with a quality factor based on pulse quality. The AI model learned patterns from structured data, including pre-processed features and initialization measurements, ranking their importance.

Hypothesis:
cuffless PPG-based-wristband method for continuous BP monitoring is compatible with ISO 81060-2:2019.

Methods:
Compare PPG-guided BP algorithm predictions with subclavian arterial reference measurements during cardiac catheterization. Consecutive patients meeting ISO 81060-2:2019 criteria were included. Reference measurements used a validated invasive BP device (100Hz). PPG signals were collected at 128Hz using six light emission diodes and two photodiodes. Three initialization measurements with a validated cuff were taken before catheterization. Machine learning-based BP algorithm utilized 100+ features. Correlation, mean error, and standard deviation (SD) and sBP and dBP were determined.

Results:
97 patients provided 420 samples. Mean age, weight, and height were 67 years, 183.7 lbs, and 5'8.5" respectively. sBP swas ≤100mmHg (11%) and ≥160mmHg (25%). dBP was ≤70mmHg (53%) and ≥85mmHg (24%). BP algorithm predictions correlated strongly with reference measurements for sBP (r = 0.985) and dBP (r = 0.961) BP. Mean error was ±3.7mmHg (SD 4.4 mmHg) for sBP and ±2.5mmHg (SD 3.7 mmHg) for dBP. Results were consistent across gender and skin color categories (Fitzpatrick I-VI), but also for different strata of BP values.

Conclusions:
Wristband-based PPG with the developed BP algorithm provides accurate continuous BP monitoring across various BP ranges. It offers a valid and less burdensome alternative to cuff BP measurements for in-hospital and at-home monitoring. Further research is needed to evaluate algorithm precision during movement and for long-term prediction stability.
Abstract 17715: Heart Rate Reduction Alone Produces Reverse Remodeling in Heart Failure Patients Refractory to Beta-Blockers: The PROBE-IT Trial
Authors: Altman Natasha , Meyer Leslie K , Kahwash Rami , Karimpour-Fard Anis , Wagner Jessica , Gill Ed , Kao David P , Minobe Wayne , Abraham William T , Emani Sitaramesh , Jonas Eric , Ellis Sam , buttrick peter , Bristow Michael R
Published: December 2023

In a 2-center trial (
P
ulse
R
eduction
o
n
Be
ta-Blocker and
I
vabradine
T
herapy (PROBE-IT)) we tested the hypothesis that failure to adequately reduce heart rate (HR) contributes to non-response to beta-blockers. Twenty-two dilated cardiomyopathy patients (DCM) with a sinus rhythm (SR) heart rate (HR) ≥70 bpm without reverse remodeling after target doses of beta-blockers were randomized 2:1 to 5±2.5 mg b.i.d of ivabradine (IVB) or matching placebo, and treated for 24 weeks with continuation of beta-blockers. Echocardiograms for LVEF measurements and endomyocardial biopsies for measurement of global gene expression by RNA-Sequencing were performed at baseline and end of study. The protocol design aimed for approximately equal numbers of patients with a HR reduction (HRι) and a control group with no change in HR (HRν), with the predefined statistical analysis plan comparing subjects above and below the median HR change. Characteristics and changes from baseline in the 17 patients who completed the trial were (*P <0.05,
†
P <0.01 vs. HRν):HRν patients had a longer duration of HF,, 112 months vs. 35 months in HRι (P = 0.005). In HRι vs. HRν, gene expression findings included 18 mRNAs at a P <0.0005 and 39 at a P of <0.001 with higher abundance, and 34 (P <0.0005) and 94 (P <0.001) lower abundance. The classification of these genes was distinct from molecular changes described for reverse remodeling from beta-blockers alone, with only a 2.1% overlap. Gene expression changes that could have contributed to reverse remodeling in HRι included: increases in
NRG1
(neuregulin 1),
PP1R3C
(protein phosphatase 1), and multiple mitochondrial electron transport genes; and lower expression of genes encoding cardiotrophin-1 cytokines (CTF1 and CLCF1).

Conclusions:
In NDC patients meeting the PROBE-IT entry criteria, HR lowering produces a substantial increase in LVEF accompanied by gene expression changes that differ from those associated with beta-blocker therapy.
Abstract 17721: Loss of p22
phox
Exacerbates Heart Failure Through Increased Oxidation and Proteasomal Degradation of SERCA2a
Authors: Titus Allen S , Nakada Yasuki , Mizushima Wataru , Zhai Peiyong , Oka Shinichi , Sadoshima Junichi
Published: December 2023

Introduction:
Downregulation of sarcoplasmic/endoplasmic reticulum (SR/ER) Ca2+ ATPase 2a (SERCA2a) accentuated by oxidative stress is a major driver of heart failure. NADPH oxidase (NOX) complexes are the key sources of reactive oxygen species (ROS) in cardiomyocytes. p22
phox
, a transmembrane partner of NOX1-4, plays an essential role in mediating ROS production in multiple NOX complexes. We investigated the role of p22
phox
in oxidative stress and SERCA2a levels during pressure overload (PO).

Question:
Does loss of p22
phox
alleviate heart failure through reduction of oxidative stress and stabilization of SERCA2a levels during PO?

Methods:
Cardiac-specific

p22
phox

knockout (

p22
phox

-cKO) mice were subjected to sham operation or transverse aortic constriction (TAC). The p22
phox
interactome was analyzed by co-immunoprecipitation and mass spectrometry. Protein cysteine oxidation was probed by biotinylated iodoacetamide labelling.

Results:
The

p22
phox

-cKO mouse heart showed a 50% reduction in H
2
O
2
levels compared to WT after 1-week TAC (p<0.01). Unexpectedly,

p22
phox

-cKO mice had 20% higher mortality (p<0.05), lung congestion (2-fold, p<0.05), and fibrosis (>40%, p<0.01) and a lower (40%, p<0.01) left ventricle ejection fraction than WT after TAC. p22
phox
directly interacted with SERCA2a. Lack of p22
phox
led to oxidation of SERCA2a at cysteine 498 and promoted degradation of SERCA2a. SERCA2a C498S knock-in mice have better cardiac function and stable SERCA2a protein levels after TAC compared to WT mice. Further, p22
phox
aided thioredoxin 1 (TRX-1) interaction with SERCA2a and prevented cysteine oxidation. SERCA2a was co-immunoprecipitated with Smad ubiquitination regulatory factor 1 (Smurf1) and HMG-CoA reductase degradation protein 1 (Hrd1) E3 ubiquitin ligases in the absence of p22
phox
or TRX-1.

Conclusion:
p22
phox
recruits TRX-1 to SERCA2a, prevents SERCA2a cysteine 498 oxidation, promotes its stability, and maintains cardiac function.
Abstract 17724: Myocardial Extracellular Matrix Proteins Involved in the Overloaded and Unloaded Heart After Myocardial Infarction
Authors: Mavropoulos Spyros Archimedes , Sakata Tomoki , Mazurek Renata , Marx Jonas , Ravichandran Anjali , Ishikawa Kiyotake
Published: December 2023

Introduction:
The cardiac extracellular matrix (ECM) is a dynamic scaffold that transmits and responds to forces that act on the heart during the cardiac cycle. While acute left ventricle (LV) unloading by catheter-based LV assist device (pLVAD) is now a therapeutic option, its impact on ECM is unknown.

Hypothesis:
The composition of LV ECM proteins changes in response to wall stress.

Methods:
Ten Yorkshire pigs underwent the protocol in figure 1. Non-ischemic remote myocardium was processed for ECM specific proteomics. Volcano plots were constructed to determine proteins of interest and differential expression was considered as (-log10(p)>1.3 and |log2(fold-change)| >0.5). Gene ontology (GO) analysis was performed to identify associated molecular processes and biological functions. A group of age-matched pigs (n=6) that did not undergo MI induction served as reference. Immunofluorescence microscopy was performed to validate differential expression.

Results:
Of the 986 proteins analyzed, 39 were significantly differentially expressed between overloaded and unloaded hearts. GO analysis by molecular function revealed that differences tending towards RNA binding and lipid binding proteins. Analysis by biological process showed that cell differentiation, vesicle transport, and programmed cell death were the processes most favored. Staining for three of the identified differentially expressed proteins (figure 2) had results congruent with proteomic analysis.

Conclusions:
There were significant differences in the protein composition of the cardiac ECM between acutely unloaded and overloaded myocardium, suggesting that it actively responds to altered LV load.
Abstract 17742: Anterior Papillary Muscle Rupture After a Motor Vehicle Collision: A Rare Case of Torrential Tricuspid Regurgitation After Blunt Cardiac Injury
Authors: Potarazu Deepika , Peer Syed , ferrada paula
Published: December 2023

Introduction:
Blunt cardiac injury is difficult to diagnose in the setting of polytrauma. Here we present a rare case of a torrential tricuspid regurgitation from a ruptured anterior papillary muscle after a motor vehicle collision (MVC).

Case:
A 55-year-old male presented to the ED after an MVC. He was hemodynamically unstable and hypoxic en route complaining of severe chest and left leg pain. Imaging demonstrated multiple rib fractures, a left acetabular fracture, and left open distal femur fracture. EKG identified atrial fibrillation with RVR and nonspecific ST changes. Labs were significant for leukocytosis and a troponin elevation to 11.98 concerning for blunt cardiac injury. A TTE demonstrated a mobile density in the RA and RV consistent with papillary muscle rupture and severe tricuspid regurgitation. An underfilled left ventricle compressed by the right heart and dilated RV were noted with septal flattening consistent with RV pressure and volume overload. Cardiothoracic surgery was consulted and recommended delayed tricuspid valve repair after other acute injuries were addressed considering the need for full anticoagulation. While in the ICU, his orthopedic injuries were addressed though his hemodynamics were complicated by frequent orthopedic interventions requiring blood transfusions. He later underwent TV replacement and it was found that the anterior papillary muscle was ruptured at its base without leaflet perforation. One week post-operatively the patient suffered a hypoxic PEA arrest. The shock team was consulted and he underwent bedside ECMO cannulation with impella placement for LV failure. After ten days on ECMO he was decannulated. Ultimately, the patient recovered well and was discharged to acute rehab.

Discussion:
MVCs are a leading cause of traumatic tricuspid insufficiency. However, this life-threatening condition may go undetected due polytrauma and the presence of coexisting distracting injuries. Guidelines are needed for the specific management of traumatic tricuspid regurgitation and associated right heart dysfunction. Additionally, the need for multiple surgical interventions can preclude anticoagulation which is a unique barrier to urgent valve replacement in these patients.
Abstract 17755: Post-Cardiac Injury Syndrome From Robotic Atrial Septal Defect Closure: A Case of Recurrent Pericarditis
Authors: Yaker Zachary S , Syed Alveena B , Bayat Aqieda , Saraswati Ushasi , Ali Ambreen F , Dong Tiffany , Tornekar Vineet , Klein Allan L
Published: December 2023

Case Presentation:
A 23-year-old female rugby player presented for recurrent chest pain. She has a history of atrial septal defect (ASD) repaired with robotic ASD closure. She developed acute pericarditis postoperatively and was treated with naproxen and colchicine inpatient. Her subsequent recurrences occurred with playing rugby and were treated with ibuprofen, colchicine, and prednisone. Electrocardiogram showed sinus bradycardia at 59 beats per minute but without ST segment changes. Cardiac magnetic resonance (CMR) imaging showed mild-to-moderate circumferential pericardial late gadolinium enhancement (LGE) without signal hyperintensity on T2 STIR imaging. She was diagnosed with chronic recurrent pericarditis secondary to post-cardiac injury syndrome (PCIS) and was started on rilonacept. On follow-up after 1 year, the patient remained symptom-free. She gradually increased her activity level to walking 3 miles per day and weaned down to rilonacept monotherapy. Repeat CMR showed mild pericardial LGE that was improved from before.

Discussion:
PCIS is a known cause of pericarditis due to local and systemic inflammatory responses to cardiothoracic surgery. Robotic ASD closure is a minimally invasive endoscopic procedure that has a favorable safety profile; PCIS is not a previously documented complication. Treatment of pericarditis secondary to PCIS includes NSAIDs plus 3 months of colchicine for acute pericarditis, NSAIDs plus 6 months of colchicine for a first recurrence, with corticosteroids or interleukin-1 inhibitors added for further recurrences. Incomplete treatment of acute pericarditis, as in this patient's case, is a risk factor for recurrent pericarditis. The risk of recurrences with physical activity is debated and current guidelines recommend restriction from physical activity until there is no evidence of active disease, though the data is not robust. In clinical practice, a gradual return-to-play program is frequently utilized.
Abstract 17764: Clinical Outcomes and Predictors of Vasoplegia in Patients Undergoing Orthotopic Cardiac Transplantation at a High-Volume Single-Center
Authors: Wilbur Jameson G , Wright Jonathan , Navari Yasaman , Abdel-Rasoul Mahmoud , Modi Sujal , Britto Nevin , Binda Nkongho , Whitson Bryan , Ganapathi Asvin , Smith Sakima A
Published: December 2023

Background:
Patients undergoing heart transplantation are at significant risk of the developing post-operative vasoplegia, which is associated with poor outcomes. Despite significant burden to these patients, risk factors for development of vasoplegia are poorly understood. We assess these risk factors and outcomes in patients undergoing orthotopic heart transplant at our high-volume academic center.

Methods:
173 patients underwent cardiac transplantation between January 1
st
, 2015 and February 28
th
2022 at the Ohio State University Wexner Medical Center. Baseline demographics, operative characteristics, peri-operative management, and long-term follow-up data were obtained. Vasoplegia was defined as provider documentation of vasoplegia for patients with persistent hypotension requiring the use of one or more vasopressors to maintain mean arterial pressures >65 mmHg in the absence of other explainable causes (cardiogenic shock, sepsis, etc.) The two primary endpoints assessed were development of vasoplegia in the 48 hours post-transplant and all-cause mortality. Statistical significance was assessed using Chi-squared, analysis of variance, or Kruskal-Wallis where appropriate.

Results:
In total, 173 patients underwent cardiac transplantation. 89 (51.4%) developed vasoplegia in the post-operative period. 130 (75.1%) were males. The average age at transplant was 56 years. Patients with vasoplegia were more likely to have history of atrial fibrillation (p=0.01) and had higher BMI (p<0.01) compared to those without. There were otherwise no significant differences in demographic data such as past medical history and medication history in those with and without vasoplegia. Patients with vasoplegia had significantly higher cardiopulmonary bypass times (p=0.01), aortic cross-clamp times (p<0.01) and need for red blood cell transfusion peri-operatively (p=0.02). Patients with vasoplegia had higher 30-day mortality (p=0.03), however there was no significant difference in 1-year mortality for those with and without vasoplegia.

Conclusions:
Vasoplegia is common following orthotopic heart transplant, and short-term mortality is high. Appropriate risk-stratification is paramount in caring for these high-risk patients.
Abstract 17788: Long-Term Impact of Previous Severe Preeclampsia on Heart and Large Artery Structure and Function
Authors: Bortolotto Luiz , Verardino Renata , Andrade De Macedo Thiago A , Rodrigues Sara , Costa-Hong Valeria , Baptista Fernanda , Francisco Rossana , Bortolotto Maria
Published: December 2023

Introduction:
Women with previous history of preeclampsia (PE) are at risk of cardiovascular events.

Hypothesis:
To evaluate subclinical cardiovascular repercussions by noninvasive methods in women with previous severe PE.

Methods:
Cross-sectional study was carried out in a tertiary hospital. Women evaluated 2 to 5 years after delivery and divided into 3 groups: isolated preeclampsia (IPE=30), superimposed preeclampsia and/or chronic hypertension (Sup/HC)=60 and normal gestation (NG) =30. Variables analyzed: age, body mass index (BMI), systolic blood pressure (SBP) and diastolic BP (DBP) by ambulatory blood pressure monitoring (ABPM-24h) and office, central pressure (BPc) by Sphigmocor®; pulse wave velocity-PWV by Complior® e echocardiogram (ViviDI-GE®).

Results:
Clinical
: Age (years): (Sup/HC=38 vs NG=34,6 vs IPE= 31, p <0,001). BMI (kg/m2): Sup/HC=32,6 vs NG=27,1 vs IPE=28,4, p< 0,001); SBP (mmHg): ABPM-24h (awake): (Sup/HC=128,4 vs NG=117,5, p<0,004); office: (IPE=124,8, Sup/HC=133,6 vs NG=114,6, p <0,001). DBP (mmHg) : office (IPE=80,4;Sup/HC=87,8 vs NG= 73,3) and (Sup/HC=87,8 vs IPEH= 80,4), (p<0,001); SBPc (IPE=115,4, Sup/HC=124,4 vs NG 105,8, p < 0,001). DBPc: (Sup/HC=88,8 vs NG= 75; Sup/HC=88,8 vs IPEH=81,8, p<0,001);
Vascular
: PWV (m/s) (Sup/HC=8,1 vs NG=6,8, IPE=7,0, p<0,012);
Echocardiogram
: Septum wall thickness (mm) (IPE=9,2 vs Sup/HC=9,7, NG=8,4, p<0,004); left atrium (mm) (Sup/HC=38 vs IPE=36 vs 34, p<0,005); left ventricle mass index (g/m2) (Sup/HC=81 vs IPE=80 vs. NG=66, p<0,002),

Conclusions:
Women with previous IPE had elevated BP values and cardiac repercussions compared to previous normal gestation while previous superimposed or chronic hypertension had also elevated BP, vascular and cardiac impairment compared to other previous gestational conditions.
Abstract 17801: Age-Specific Normal Values for Myocardial Blood Flow on 82rb Positron Emission Tomography
Authors: Metzinger Mark P , Ibrahim Ali , McGhie A I , Thompson Randall C , Bateman Timothy M , Sperry Brett W
Published: December 2023

Introduction:
Positron emission tomography (PET) myocardial perfusion imaging (MPI) is utilized to evaluate ischemia along with myocardial blood flow (MBF). The ability to adequately augment blood flow, measured by myocardial blood flow reserve (MBFR), is a measure of overall health of the coronary circulation and associated with lower major adverse cardiovascular events (MACE) and all-cause mortality. The age-specific ranges of MBFR in patients without demonstrable coronary artery disease (CAD) has not been well established.

Hypothesis/Aim:
To determine the effect of age on MBF and MBFR in a cohort of patients without demonstrable CAD.

Methods:
Patients who underwent PET MPI studies from 2012-2022 on Siemens PET/CT cameras were included if Summed Stress Score=0, coronary calcium score=0, and left ventricular ejection fraction ≥50%. Those with prior history of MI or coronary intervention, heart/kidney/liver transplant, cirrhosis, or CKD stage IV+ were excluded. MBF was calculated using a net retention model (ImagenQ, Cardiovascular Imaging Technologies, Kansas City, MO) and multivariable linear regression models were developed to predict MBF.

Results:
Among 3,235 patients (age 59.5+/-12.6 years, 24.2% male) with median rest MBF 0.74 [0.61-0.92] and stress MBF 1.71 [1.41-2.10], MBFR was 2.28 [1.93-2.72]. With increasing age, rest MBF remained fairly stable while stress MBF and MBFR decreased, such that for every 10 years of age, stress MBF decreased by 0.07 [95% CI 0.05-0.08] mL/min/g and MBFR decreased by 0.12 [95% CI 0.11-0.14] after multivariable adjustment. Age-specific predicted MBFR values are documented in the Table.

Conclusions:
In patients without demonstrable CAD, the MBFR decreases with age. Abnormal MBFR values under 2.0 may be seen in a significant number of older patients.
Abstract 17826: Plasma Biomarkers of Endothelial Dysfunction and Myocardial Fibrosis in Relation to Measures of Coronary Microvascular Disease in Ischemia With No Obstructive Coronary Arteries
Authors: Shekarestan Shajan , Ekenback Christina , Jokhaji Fadi , Lorstad Samantha , Wallen Hakan , Törnerud Mattias , Ljungman Petter , Samad Bassem , Linder Rickard , Persson Jonas
Published: December 2023

Background:
Increased hyperemic microcirculatory resistance and/or low coronary flow reserve (CFR) diagnostic criteria for coronary microvascular disease in ischemia with no obstructive coronary arteries (INOCA). For optimal therapy pathophysiological mechanisms need to be determined.

Aim:
To investigate plasma levels of markers of i) endothelial dysfunction (syndecan-1, E-selectin, thrombomodulin and hyaluronan) and ii) myocardial fibrosis (procollagen type I carboxy-terminal propeptide [PICP], suppression of tumorigenicity 2 [ST2], and tissue inhibitor of metalloproteinases-1[TIMP-1]) in relation to the index of microcirculatory resistance (IMR) and CFR in INOCA.

Methods:
Measurements of corrected IMR and CFR were determined in the LAD using thermodilution technique during coronary angiography (CA) in chronic coronary syndrome (CCS) patients. Plasma biomarkers were quantified using an ELISA and the association between each biomarker and i) IMR and ii) CFR was analyzed using linear regression.

Results:
We selected 162 random patients with INOCA from a cohort of 503 all-comer CCS patients with no congestive heart failure that underwent CA with measurements of CFR and IMR in the LAD. The mean age was 65 ±10 years and 101 (62.3%) were male. Median IMR and CFR were 19.1 (interquartile range [IQR] 11.9-30.7) and 3.5 (IQR 2.3-5.1) respectively. IMR was associated with syndecan-1 (Figure 1A) but not with PICP (Figure 1C) or the other biomarkers. CFR was inversely associated with syndecan-1 (Figure 1B), PICP (Figure 1D), and E-selectin (p=0.049).

Conclusion:
IMR is associated with increasing plasma levels of syndecan-1 but not with myocardial fibrosis, indicating endothelial dysfunction, with glycocalyx shedding, to be involved in high hyperemic microcirculatory resistance in INOCA. Low CFR is also associated with PICP indicating involvement of myocardial fibrosis in coronary microvascular disease in INOCA.
Abstract 17829: Improving Access to Cardiac Rehabilitation for Minorities and Vulnerable Patients With a Multidisciplinary Program in a Large Metropolitan Public Hospital Network
Authors: Padilla Lopez Mireia , Alviar Carlos , Glenn Matthew , LeRoy Erik , Kang Susan , dunham-hoshida nikki , Keller Norma , Signorastri Alaina , Vorsanger Matthew H
Published: December 2023

Introduction:
Cardiac rehabilitation (CR) improves outcomes after myocardial infarction, cardiac surgery or in chronic heart failure with reduced ejection fraction. However, access to CR is often limited to insured patients or those who can pay out-of-pocket, leaving uninsured or undocumented patients without access to these benefits. Our aim is to describe the implementation and outcomes of a multidisciplinary comprehensive CR program in the largest public health system in the country, as a strategy to mitigate healthcare disparities and improve access to care for minorities.

Methods:
Our CR program started in March 2021 as a virtual program and opened for in-person care in November 2022. We collected clinical, demographic, socioeconomic, and immigration data as well as data on clinical outcomes such as hospital readmission, mortality, and program completion rates.

Results:
A total of 202 patients were included (35.6% women, mean age 62), with 83.7% of patients in virtual CR and 16.3 % in in-person CR. The most common ethnic group was Black (41.6%) followed by Hispanic (38.6%). A total of 23.8% were uninsured, 21.3% were undocumented and 52.5% lived below the poverty level reported for New York City. The highest level of education was
<
8th grade in 16.8%, high school in 22.8%, at least 2 years of college in 5.5%, > 4 years of college in 7.9% and unknown in 47%. The hospital readmission rate at 6 months was 12.4% and mortality was 1.5%. There were no significant differences in survival or readmission by ethnic group. Of patients completing at least one visit, 72% were active or graduated from virtual CR and 90% were active or graduated for in-person CR (Figure).

Conclusions:
Our multidisciplinary CR program demonstrates feasibility in providing care to underserved and vulnerable populations, showing excellent results and providing a strategy to decrease healthcare disparities in access to an intervention which improves outcomes across a broad spectrum of cardiac disease.
Abstract 17833: Characterization of Central versus Peripheral Predominance of Exercise Limitation in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Prasad Cheshta , Campain Joseph , Minasian Alexandra , Griskowitz Catharine , Giverts Ilya , McGinnis Shaina , Rouvina Jennifer , Kowal Alyssa , Kelly Katherine , White Casey , Wagner Peter , Malhotra Rajeev , Lewis Gregory
Published: December 2023

Background:
Heart failure with preserved ejection fraction (HFpEF) is a heterogenous disorder in which abnormalities in both cardiac output (CO) and peripheral oxygen extraction (CavO
2
) contribute to impaired oxygen uptake (VO
2
). We investigated the predominant limitation to VO
2
, according to distinct HFpEF criteria, by examining the CO vs. VO
2
relationship during incremental exercise.

Methods:
Participants underwent Cardiopulmonary Exercise Testing (CPET) with invasive hemodynamic assessment and were diagnosed with HFpEF based on characteristic symptoms and NTproBNP ≥125pg/mL, Supine PCWP ≥15mmHg, PCWP/CO ≥2mmHg/L/min or Peak PCWP ≥25mmHg. Calculated direct Fick CO versus VO
2
slope and peak exercise data were stratified by the expected relationship of CO(L/min) = 5хVO
2
(L/min) +5. The Mann Whitney U Test and t-test characterized those limited by cardiac output (Slope <5L/min) vs. peripheral extraction (Slope >5L/min).
Results:
In 425 dyspneic individuals meeting biomarker and/or hemodynamic criteria for HFpEF, 36% had predominantly peripheral limitation (Measured Peak CO > Expected). Among those with NTpro-BNP ≥125pg/mL or resting PCWP ≥15mmHg, or both
(N=220)
, 31% were peripherally limited. 41% of those with a PCWP/CO ≥2mmHg/mL/min or Peak PCWP ≥25mmHg, or both
(N=205)
, were peripherally limited. Among all peripherally limited patients (N=151), the percentage of females, NTpro-BNP levels, Hb levels, rest and peak Ca-vO
2
, and rest and peak PVR were significantly lower compared to the cardiac limited group (Table, N=274), while resting PCWP, LVEF and HR were similar (Table).

Conclusion:
Despite meeting concurrent biomarker and/or hemodynamic criteria for HFpEF, peripheral-predominant limitation to exercise capacity is common which merits consideration when deploying interventions to augment exercise capacity in HFpEF.
Abstract 17843: Direct Oral Anticoagulants versus Low Molecular Weight Heparin for Venous Thromboembolism in Cancer Patients: An Updated Systematic Review and Meta-Analysis
Authors: Akbar Usman , Mughal Ahmad Kabir , Khan Ahmad Ali , Umer Ahmed Muaaz , Malik Saad U , Shamshad Talha , ALI AHMED , Shafique Nouman , Danish Ali , Anwar Rana Usman , Rasool Muhammad Wajid , Taj Sobaan , Qazi Shaheryar , Muhibullah - , Basit Jawad , Dani Sourbha
Published: December 2023

Introduction:
Patients with cancer have an increased risk of venous thromboembolism (VTE). We aim to evaluate the risk of recurrent VTE and major bleeding in patients with cancer when started on DOACs versus low molecular weight heparin (LMWH).

Methods:
We conducted a systematic literature search according to PRISMA guidelines to identify studies using the terms: “venous thromboembolism,” “low molecular weight heparin,” and “direct oral anticoagulants.” After the screening, We extracted the data until May 2023 in a data extraction sheet. Our inclusion criteria were: adult patients, and cancer patients, who were on DOACs or LMWH for VTE or atrial fibrillation. We used a variance-weighted random-effects model to analyze data on DOACs vs. LMWH, estimating event rates and odds ratios while assessing heterogeneity. Data were analyzed using the ‘meta’ package in R.

Results:
Our analysis included 16 studies (n= 12216 patients). Cancer patients on DOACs significantly reduced the risk of recurrent VTEs compared to LMWHs OR 0.69 (95% CI: 0.56- 0.86, I 2:23% ). However, for major bleeding and clinically relevant non-major bleeding, although the statistical significance was not reached, a consistent trend favoring DOACs was observed (OR = 0.92, 95% CI: 0.65-1.30) and OR=1.19 (0.90-1.59) respectively. (Figure1)

Conclusions:
Among cancer patients, DOACs are associated with a significantly lower risk of recurrent VTEs than LMWHs. Although the statistical significance was not reached for major bleeding and clinically relevant non-major bleeding, there was a trend favoring DOACs over VKA. Increased recruitment of cancer patients in clinical trials is needed to provide us with updated data to refine treatment strategies.
Abstract 17845: Logic-Based Natural Language Processing Identifies VT Recurrence in the Electronic Health Record
Authors: Brennan Kelly A , Feng Ruibin , Goyal Jatin , Azizi Zahra , Baykaner Tina , Rogers Albert J , Narayan Sanjiv M
Published: December 2023

Introduction:
With the advent of integrated electronic healthcare record (EHR) systems, it is increasingly important to identify patients who may suffer a clinical endpoint to allocate resources and develop predictive models. For the endpoint of VT recurrence after ablation, outcomes are currently assessed manually by experts, which is time consuming with few automated tools. We set out to develop a robust natural language processing model to parse cardiology and electrophysiology notes to detect VT.

Hypothesis:
We hypothesize that natural language processing (NLP) with logic-based algorithms can be used to accurately extract specific information on VT recurrence from complex clinical notes, compared to experts.

Methods:
We studied N=639 full-text clinical notes written by board certified cardiologists from N = 125 patients (32.0% female, LVEF 48.9±13.9%, 61±14.0 years). Notes were labeled as “No” or “Yes” for VT recurrence, and split into a development set of N=303 (median word count = 236) from N=75 patients and a test set of N=336 (median words = 297) from N=50 patients. We developed an NLP rule based expert system that uses hierarchical groups of keywords to identify sentences related to VT, then uses negation and quantifier functions to interpret context and assign a label.

Results:
The logical flow is shown in figure A. This approach achieved an 93.73% accuracy in the development set (precision = 57.14%, recall = 69.56%), and 90.48% accuracy (precision = 36.84%, recall = 63.63%) in the test set (figure B).

Conclusions:
An NLP logic-based approach can identify VT recurrence post ablation from complex clinical notes. NLP can thus be used to accelerate data extraction for clinical purposes or for semi-supervised learning. Future work will determine if logic-based NLP need to be augmented for noisier data, such as the entire EHR system.
Abstract 17853: Efficacy of Grace Score for Prediction of Mortality in Patients of Acute Coronary Syndrome: A Meta-Analysis
Authors: Basit Jawad , Zaheer Zaofashan , Yasmin Farah , Khan Laiba , Cheema Huzaifa Ahmad , Hamza Mohammad , Aamir Muhammad , Akbar Usman , dhama kuldeep , Rajeshkumar Chitra Shanjeev Kumar K , Saeed Sajeel , Rehman Mohammad E , Malik Jahanzeb , Alamzaib Sardar Muhammad , sattar yasar , Alraies M Chadi C
Published: December 2023

Introduction:
The Global Registry of Acute Coronary Syndrome (GRACE) is a validated risk prediction model for acute coronary syndromes (ACS). However, discrimination ability of this model for predicting mortality in ACS remains unclear. The aim of this meta-analysis is to determine the predictive accuracy of GRACE score for mortality in ACS patients.

Methods:
A comprehensive literature search was conducted across MEDLINE, Embase & the Cochrane Library from inception till May 2023. All studies that reported the C-statistic for predicting in-hospital, 6-month, 1 year & 2-year mortality in ACS patients were included. The generic inverse variance weighted random effects method was used to pool C-statistics & corresponding standard errors (SEs) from each study. Subgroup analysis was conducted based on whether the patients required percutaneous coronary intervention (PCI) or not.

Results:
A total of 22 studies with a patient population of 132856 were included. For in-hospital mortality (n=99774), the GRACE score showed a good discrimination ability to predict mortality (summary C-statistic 0.86 [0.85-0.87], I
2
=58%). The pooled C-statistic for 6-month mortality (n=24174) was 0.80 (0.70-0.84; I
2
=93%). For 1-year mortality (n=13517), the predictive accuracy of the GRACE score was moderate (summary estimate= 0.77 [0.70-0.83]; I
2
=94%). The GRACE score proved to be moderately accurate in predicting 2-year mortality (n=4972) in ACS patients [0.75 (0.66-0.83); I
2
=66%]. All the findings were consistent across the two subgroups of PCI vs no PCI (p for interaction >0.05).

Conclusion:
The GRACE score is a simple scoring system that demonstrated good predictive ability for in hospital mortality, & at 6-months while moderate predictive ability for the risk of death at 1-year, & 2-year in patients of ACS with & without PCI.
Abstract 17855: Improvement of Mitral Valve Regurgitation Severity Following Catheter Ablation for Atrial Fibrillation
Authors: Rahgozar Kusha , Apple Sam , MATHAI Sheetal vasundara , Alhuarrat Majd Al Deen , Marashly Qussay , Gabr Mohamed , Reynbakh Olga , Jorde Ulrich P , Di Biase Luigi
Published: December 2023

Background:
The presence of concomitant mitral valve regurgitation (MR) in patients with atrial fibrillation (AF) is well known, yet the degree of MR improvement after catheter ablation is not well studied. We investigated the effect of catheter ablation on the degree of MR in patients with baseline ≥moderate MR and AF.

Methods:
We retrospectively reviewed charts of AF catheter ablation patients at Montefiore Medical Center (2018-2019). Patients with prior or subsequent mitral valve surgeries were excluded. Degree of MR, assessed through echocardiograms, was compared at baseline and follow-up. Early follow-up was defined as 6 months post-ablation. Patients were stratified by left atrial size and left ventricular ejection fraction (LVEF) to assess the influence of these parameters on MR severity after ablation.

Results:
A total of 202 patients were included in our analysis with an average age of 64 years. At baseline there were 149 patients (74%) with <moderate MR and 44 patients with ≥moderate MR (22%). There was a statistically significant reduction in the number of patients with ≥moderate MR following ablation both at early and late follow-up (p<0.0001, Figure 1). Our results remained statistically significant after stratification by LVEF (<40% vs ≥ 40%) and LA dimension (<4.5cm vs ≥ 4.5cm) (p<0.001, Figure 2).

Conclusions:
Catheter ablation of AF improved the degree of MR severity in patients with baseline ≥moderate MR and AF. Our findings were preserved across stratification by left atrial size and LVEF subgroups. Further investigation is necessary to validate our findings.
Abstract 17865: Machine Learning With Multimodal Pre Ablation Imaging for Predicting Recurrence in Atrial Fibrillation Patients
Authors: Midya Abhishek , Asaeikheybari Golnoush , Hiremath Amogh , Viswanathan Vidya Sankar , Sun Han , Harwood Samuel , Kim Hyun Su , Schilling Taylor , Telfer William , Jin Alison , Baraboo Justin , Pradella Maurice , Markl Michael , Passman Rod S , El-Harasis Majd , Shoemaker Ben B , Tandon Animesh A , Barnard John , Chung Mina K , Madabhushi Anant
Published: December 2023

Purpose:
Catheter ablation is a popular treatment option for atrial fibrillation (AF), but AF recurrence is common. Currently, no marker exists to reliably predict the risk or location of recurrence (AF+). In this work, a multimodal imaging approach was employed to identify surface of interest (SOI) associated with recurrence using pre-ablation MRI and CT scans.

Hypothesis:
Shape of the left atrium (LA) plays a critical role in AF recurrence. The difference between AF+ and AF- may be identified on pre-ablation scan and may find potential sites for additional pre-emptive ablation. Method: Two representative template scans were selected from each group and all patients were registered to these respective templates to develop an atlas for each group. The two atlases were then co-registered, and the difference areas were obtained using a t-test with 500 permutations. The SOI was identified as the area that showed statistically significant (p <0.05) differences between the AF+ and AF-. The process was repeated 5 times to obtain most frequent SOI. Since no ground truth for SOI exists, we used a multimodal imaging approach to construct atlases on CT and MRI; the corresponding SOIs were compared.

Results:
102 CT (51 AF+) and 160 MRI (79 AF+) scans collected from Cleveland Clinic and Vanderbilt University were randomly sampled 5 times. At each iteration 20 patients from AF+ and AF- patients were randomly chosen and employed to create atlases for generating SOIs. The dice sore of MRI and CT derived SOI were 0.75± 0.08 and 0.82±0.05, respectively. The SOI region was below the LA appendage and left inferior pulmonary vein on both CT and MRI. The ratio of significant region to LA volume were [9%-18%] and [8%-19%] for CT and MRI, respectively indicating a good agreement between two SOIs.

Conclusion:
We identified SOI associated with AF+ from CT and MRI and found correlation between them at sites expected to be near the vein of Marshall, an area increasingly targeted for recurrent AF after prior ablation.
Abstract 17879: Assessing the Safety of an Early Repatriation Strategy for Uncomplicated ST-Elevation Myocardial Patients After Primary Percutaneous Intervention
Authors: Brar Shanjot , Khan Razi , Hosseini Farshad , Chan Albert , Charania Jahangir , Philipp Roger , Vo Minh , Vuurmans Tycho , Kohli Natasha
Published: December 2023

Introduction:
Repatriation of patients with ST-elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI) is common in Canadian regional health care programs. However, the safety of early repatriation after PPCI in uncomplicated STEMI patients remains unknown. We aimed to compare the outcomes between uncomplicated STEMI patients repatriated early (transfer to home hospital ≤4hrs of PPCI completion) vs. those who remained at the PPCI-hospital until discharge.

Methods:
We performed a retrospective, cohort study examining consecutive, uncomplicated STEMI patients treated with PPCI between 2016-2018 in the Fraser Health Authority. Patients were designated as uncomplicated if there was no evidence of cardiogenic shock, prolonged cardiac arrest or congestive heart failure requiring mechanical ventilation. Outcomes of interest included discharge with guideline-based medical therapy (GBMT) and a composite of 1-year major cardiovascular events.

Results:
A total of 787 patients were included for analysis, with 62% (n=492) being repatriated early. Early repatriated patients were similar in age and baseline characteristics when compared with those discharged from the PPCI-based hospital. Interestingly, early repatriated patients were more likely to be discharged on GBMT (89% vs. 83%, p=0.015) In multivariate analysis, early repatriation was not associated with worsened 1-year cardiovascular outcomes (OR 1.05, 95% CI 0.6782,1.6521, p=0.80). Independent predictors of 1-year major cardiovascular outcomes included hypertension (OR 1.75, 95% CI 1.0918-2.8349, p=0.02) and discharge with GBMT (OR 0.49, 95% CI 0.2831-0.8465, p=0.01). Amongst the subset of early repatriated patients, primary treatment by cardiologist vs internist did not result in differences in 1-year outcomes (10% vs. 8%, p=0.23) or discharge with GBM (87% vs. 83%, p=0.09).

Conclusions:
Early repatriation of uncomplicated STEMI patients after PPCI was associated with outcomes similar to those having ongoing care at the PPCI-based hospital. Therefore, early repatriation serves as a safe treatment strategy for regional STEMI programs and may be particularly relevant for PPCI centres with limited bed capacity.
Abstract 17896: Implantable Cardioverter Defibrillator in Cardiac Resynchronization Therapy Recipients With Advanced Chronic Kidney Disease
Authors: Goldenberg Ido , Kutyifa Valentina , Zareba Wojciech , Huang David T , ROSERO Spencer Z , Younis Arwa , Schuger Claudio D , McNitt Scott , Polonsky Bronislava , Steinberg John , Steinberg John S , Goldenberg Ilan , Aktas Mehmet K
Published: December 2023

Introduction:
The effectiveness of the implantable cardioverter defibrillator (ICD) in preventing sudden cardiac death (SCD) is well-established in heart failure patients with reduced ejection fraction (HFrEF). However, the benefit of the ICD in advanced chronic kidney disease (CKD) patients remains elusive, particularly in those who are cardiac resynchronization therapy (CRT) recipients.

Hypothesis:
In CRT recipients with CKD, the benefit of the ICD may be attenuated due to the competing risk of mortality before experiencing an arrhythmia.

Methods:
A total of 1015 patients receiving CRT with defibrillator (CRT-D) for primary prevention of SCD were included from the MADIT-CRT and RAID trials. Patients were categorized into two groups based on kidney disease (KD) stage: Stage 1-3a (S1-S3a) CKD and Stage 3b-5 (S3b-S5) CKD. The primary endpoint was the occurrence of ventricular tachycardia (VT) or ventricular fibrillation (VF).

Results:
The cumulative incidence of any VT/VF was 23.5% in patients with (S1-S3a)KD and 12.6% in those with (S3b-S5)KD (p<0.001 [Figure left panel]). Death without VT/VF occurred in 6.6% of patients with (S1-S3a)KD and 21.6% of patients with( S3b-S5)KD (p<0.001 [Figure right panel]). A multivariate competing risk regression model revealed that patients with (S3b-S5)KD had a 43% lower risk of experiencing any VT/VF compared to those with (S1-S3a)KD (HR=0.56, 95% CI [0.33-0.94], p=0.03). Over two years of follow-up, patients with (S3b-S5)KD had nearly a five-fold increased risk of death without VT/VF compared to those with (S1-S3a)KD (HR=4.63, 95% CI [2.46-8.72], p for interaction with time=0.012).

Conclusions:
The benefit of the ICD may be attenuated in CRT recipients with advanced CKD due to a lower incidence of arrhythmias and a higher risk of non-arrhythmic death. Future prospective trials should investigate whether CRT without a defibrillator is more suitable for these patients.
Abstract 17917: Effect of Transcatheter Aortic Valve Replacement (TAVR) on the Dicrotic Notch in Patients With Severe Aortic Stenosis
Authors: Iskandar Odette , Kathavarayan Ramu Shivabalan , Majeed-Saidan Maryam Muhammad Ali , Layoun Habib , Yun James J , Reed Grant W , Puri Rishi , Krishnaswamy Amar , Kapadia Samir R
Published: December 2023

Background:
The dicrotic notch in the aortic pressure waveform is seen around the time of closure of the aortic valve at the end of systole and the beginning of diastole. We aim to study the change in the dicrotic notch post TAVR in patients with severe AS and its impact on clinical outcomes.

Methods:
We included patients with severe AS who underwent TAVR consecutively between 2019-2020. Central aortic pressure waveforms were reviewed from the SyngoDynamics imaging software (Siemens Healthcare, Malvern, PA) for the invasive hemodynamic data obtained during TAVR. Heights of the systolic, diastolic blood pressure and dicrotic notch waveforms are measured. Dicrotic notch index (DNI) is calculated as the difference between the SBP and dicrotic notch divided by the pulse pressure (see figure 1). The invasive hemodynamics are compared between pre and post TAVR using independent samples t test. Statistical significance was defined as two-tailed p-value less than 0.05. Survival analysis is performed using cox regression.

Results:
A total of 724 patients (1448 studies) were evaluated. There is significant increase in dicrotic notch pressure (p<0.001) and DNI (p<0.001) post-TAVR in the overall population. Women (n=310) had a higher pre-TAVR and post-TAVR DNI (p<0.001 and p<0.01 respectively). Figure 1 shows hemodynamic characteristics of before and after TAVR. Heart failure hospitalization (HFH) or mortality at 3 years (composite outcome) was present in 146 patients (20.1%). DNI was lower in patients reaching composite outcomes compared to patients surviving without HFH (p<0.001).

Conclusion:
Higher DNI after TAVR is associated with lower HFH and mortality after TAVR. Simple measurement of DNI offer substantial prognostic value to patients with severe AS undergoing TAVR.