bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 6907: Implementing Quality Improvement With Fellow-in-Training Super Users: Preventing Preventable Strokes Initiative
Authors: Xiang Kun , Morales Jose , Becoats Kyeesha , Mikulic Sebastian , Martinez Andres , Rivas Jose , Haddad-Lacle Judella , Catalano Christina , Ash Sue , Fry Patrick , Smith Anne Marie , Martin Lowe Mary , Araia Almaz , Sadiq Hammad , Kapoor Alok , Catanzaro John N
Published: April 2024

Introduction:
Quality improvement (QI) is an integral requirement of post graduate training. To reduce stroke by addressing lack of anticoagulation (AC) for patients with atrial fibrillation (AF), the Heart Rhythm Society (HRS) led QI initiatives at metropolitan area “safety-net” hospitals, health systems that deliver a significant level of service to medically and socially vulnerable populations. We incorporated a fellow-in-training “Superuser” team in the design of a QI initiative at University of Florida Health Jacksonville.

Hypothesis:
Our hypothesis was that the use of a team of fellows in training to conduct academic detailing can enhance the impact of QI intervention

Methods:
This initiative was designed to integrate guideline-based treatment algorithms and alerts into the Electronic Health Record (EHR) and to disseminate education for the provider and patient, with emphasis on shared-decision making. An interdisciplinary team was organized among divisions of cardiology, internal medicine, family medicine, information technology and pharmacy. The first stage was to collect benchmark data to identify gaps in guideline-directed AC. EHR records from July through December 2020 were reviewed. To assist with PDSA (Plan, Do, Study, Act) interventions, a Superuser team was formed by fellows-in-training in cardiology and electrophysiology, as well as residents in internal medicine. The information technology department generated bi-weekly data reports to monitor progress. Bi-weekly Superuser meetings were held to analyze data, identify improvement strategies, and form a plan of action. A total of five PDSA cycles were planned and conducted over a 6-month period.

Results:
At benchmark, 43.67% of AF patients with a CHA
2
DS
2
-VASc score of 2 or more were untreated with AC. This percentage was reduced to 42.16% after five PDSA cycles. There were 1.5% more patients treated with AC after six months, compared to the benchmark data. This improvement in AC percentage could have resulted in the prevention of 1.5 strokes.

Conclusion:
Appropriate and sustained interventions can improve quality measurement in guideline-based AF management. Fellows-in-training can be mobilized to support these efforts. The QI initiative achieved some success and built a foundation for future outcomes-based improvement, as well as an enthusiasm for QI by fellows-in-training.
Abstract 6916: The Right Ventricle in Adolescent Athletes: Standing up for the Smaller Side
Authors: Sivalokanathan Sanjay , Augustine Daniel X , Sharma Anushka , Willis James , pearce keith , Papadakis Michael , Sharma Sanjay , Malhotra Aneil
Published: April 2024

Introduction:
Athletic training often results in changes that may mimic features of pathological cardiomyopathies. These changes are influenced by age, ethnicity and sporting discipline. Studies detailing the physiological adaptation to exercise on the right ventricle (RV) of adolescent athletes are fewer compared to the left ventricle, with even fewer describing the impact of ethnicity on the RV. One such potential physiological overlap with pathological change is arrhythmogenic right ventricular dysplasia (ARVD). An erroneous interpretation may have profound consequences ranging from false reassurance in a vulnerable athlete to unfair disqualification in a healthy individual. Therefore, it is important for the clinician to distinguish physiology from pathology.

Results:
ECG and echocardiographic data of 3000 academy male footballers were analysed, aged between 13 and 18 years old (mean age 16.4 ± 0.5 years), who underwent mandatory cardiac screening. Ethnicity was categorised as white (n=1000), black (n=1000) and mixed-race (n=1000). Overlap between ECG changes expected in ARVD and the adolescent athlete was observed. ARVD major criteria for TWI was seen in (n=63) 6.3% of the cohort. This was more prevalent in black footballers (n= 37; 3.7%) when compared to mixed race footballers (n=20; 2%) or white footballers (n=6; 0.6%), p<0.05. In up to 67% of the overall cohort, RV values exceeded those for normal adult reference ranges. Overall, 0.2% of the cohort would fulfil diagnosis for ‘definite’ ARVD and 2.2% would fulfil diagnosis for ‘borderline’ ARVD. This was seen more frequently in black footballers (n=99, 9.9%) than mixed race footballers (n=39, 3.9%) or white footballer (n=6; 0.6%), P = 0.0005. Among athletes meeting definite or borderline ARVD criteria, no cardiomyopathy was identified.

Conclusion:
This is the largest study to our knowledge that reports RV dimension data among adolescent footballers of different ethnicities. Right heart sizes in excess of standard adult ranges occurred in as many as one in 5 athletes. It is not unusual to observe values that would overlap with criteria for ARVD. As with LV parameters, variations in terms of ethnicity should be accounted for when performing routine cardiac assessments of adolescent athletes.
Abstract 6945: A Pacemaker Red Herring and a Hypertrophic Cardiomyopathy Copycat
Authors: Raber Inbar , Palmeri Nicholas , Tahir Usman A , Zimetbaum Peter
Published: April 2024

A 53-year old man with a history of hypertension, atrial flutter, and complete heart block with a dual chamber pacemaker presented to the hospital due to concern for pacemaker malfunction. Remote pacemaker monitoring found over-sensing events. He works in an automobile repair shop and his family history is notable for a son with Wolf Parkinson White syndrome treated with ablation. On presentation to the emergency department, he had normal vital signs and no lab abnormalities. His electrocardiogram showed sequential atrioventricular pacing at 60 beats per minute. He underwent an echocardiogram which showed a newly reduced left ventricular ejection fraction of 40-45% with global left ventricular hypokinesis, and left ventricular hypertrophy.

The patient’s over-sensing events were initially concerning for pacemaker malfunction, particularly because he is known to be pacemaker-dependent. The differential diagnosis for the over-sensing events included battery depletion, insulation failure, insufficient programmed sensitivity value, and electromagnetic interference. An electrogram of one of the over-sensing events revealed simultaneous over-sensing of the both the atrial and right ventricular leads and otherwise stable lead parameters, which was consistent with electromagnetic interreference during arc-welding. The differential diagnosis for the left ventricular hypertrophy included sarcomeric hypertrophic cardiomyopathy, left ventricular hypertrophy secondary to hypertension, and hypertrophic cardiomyopathy phenocopies including Danon disease, Fabry Disease, Pompe disease, and PRKAG2 syndrome. Due to his family history of pre-excitation, genetic testing was conducted and demonstrated a pathogenic variant in the PRKAG2 gene. Shared decision-making with the patient informed his choice to upgrade his pacemaker to an implantable cardioverter defibrillator for primary cardiovascular prevention. The diagnosis of PRKAG2 syndrome served as the catalyst for his family members to undergo genetic testing. This case highlights the need for a high index of suspicion for hypertrophic cardiomyopathy phenocopies when pre-excitation and ventricular hypertrophy collocate to the same patient or family.
Abstract 6996: A Deep Neural Network Model for Predicting In-Hospital Postoperative Mortality and Complications of Open-Heart Surgeries: The Shiraz Open Heart Surgery Study
Authors: Yazdanpanah Mohammad Hosein , Mahmoodian Mahnaz , Ghanaat Fateme , Nemati Mohammad Hasan
Published: April 2024

Introduction:
A reliable model for the pre-op prognostic evaluation of open-heart surgery outcomes is a worthwhile pursuit. This study aimed to develop a model to select risk variables and predict mortality and complications after open-heart surgery using deep neural networks (DNN).

Methods:
In this retrospective cohort study, data from all patients aged more than 18 years old who underwent open-heart surgery at Shiraz Central Hospital (Iran) between Nov 2004-Sep 2018 were used. Model to predict postoperative mortality and complications were constructed using DNN. For calibration, a 5-fold cross-validation technique was used, and risk variables were ranked and minimized in number by calibrated DNN. The bootstrap technique obtained mortality prediction with 95% confidence limits for each patient. Evaluation of DeepScore and other models was based on sensitivity analysis and Area Under the Curve (AUC). All the statistical analyses were performed in the Python library (scikit-learn).

Results:
A total of 6787 patients that entered the study had a mean age of 61.06±11.1 years, and 4692 (69.1%) were male. Among these patients, 94 cases (1.38%) died in hospital, 120 cases (1.77%) had respiratory complications, 259 cases (3.82%) suffered from renal complications, and 114 patients (1.68%) had neurological complications. The proposed DeepScore model (
deep.artinanalysis.com
) predicts the risk of in-hospital postoperative mortality and complications from 36 baseline pre-op variables. The AUC of the DeepScore was 0.81, which was significantly higher than the values obtained for the other models(P<0.001). The AUC of the EuroScore II model, which was ranked second was 0.71, followed by logistic regression (LR), support vector machine (SVM), random forest (RF), and gradient boosting machine (GBM) models with AUC values of 0.68, 0.67, 0.55, and 0.54 respectively.

Conclusion:
In conclusion, our DeepScore model outperformed the RF, SVM, GBM, or LR models and EuroSCORE II to predict postoperative in-hospital mortality. This model can be used preoperatively to identify patients whose baseline characteristics suggest an elevated risk for mortality and complications. Also, these patients may benefit from additional support and monitoring allocation.
Abstract 8870: Hemodynamic Impact of Atrial Pacing in Patients with Fontan Physiology and Junctional Rhythm: A Cardiac Catheterization Study
Authors: Alnoor Mohammad , Burch Grant , Armsby Laurie , Balaji Seshadri
Published: April 2024

Introduction:
Sinus node dysfunction is a common problem and can adversely impact patients who have undergone the Fontan operation (FO). In FO patients with an adequate junctional escape rhythm (JR), the benefit of atrial pacing to restore atrioventricular synchrony remains unclear. We studied the impact of atrial pacing on hemodynamics in patients with FO and JR undergoing cardiac catheterization.

Methods:
Data was collected retrospectively on all FO patients with JR who underwent atrial pacing during cardiac catheterization. Hemodynamics (pulmonary artery pressure, left atrial pressure, and cardiac index) were obtained at baseline and after atrial pacing for 5-10 minutes.

Results:
Six patients, with a mean age of 11 years (range 3-21) met inclusion criteria. The type of FO was extracardiac in 5 and a lateral tunnel in one. A pacing catheter was placed through the Fontan fenestration in 4, via the IVC recess behind the right atrium in 1, and via the left pulmonary artery in 1. Patients were paced 10 bpm faster than their JR rate (100 bpm in 3, 88 bpm in 1 and 70 bpm in 2. With pacing, there was a significant decrease in left atrial pressure from (mean ±SEM) 9.4 ± 1.1 mmHg to 5.8 ± 1.4 mmHg (p=0.02), a significant increase in cardiac index from 2.7 ± 0.4 L/min/m
2
to 3.5 ± 0.5 L/min/m
2
(p=0.03) and no significant change in pulmonary artery pressure, from 13mmHg ± 1.4 to 12.2mmHg ± 2.2 (p=0.1)

Conclusion:
In FO patients with JR, atrial pacing acutely decreased the left atrial pressure, increased the cardiac output and did not result in a significant change in the pulmonary artery pressure. Our study supports further investigation into the utility of prophylactic atrial pacemaker implantation in Fontan patients with significant durations of JR on ambulatory monitoring.
Abstract 9022: Chronic Beta3-Adrenergic Receptor Antagonist Therapy Rescues Diabetic Cardiomyopathy Through Ca
2+
/Calmodulin-Dependent Protein Kinase II Inhibition in a Type II Diabetes Murine Model
Authors: Cheng Heng , Sun Xiaoqiang , Cao Jing , Chen Zhe , Liu Yixi , Herrington David M , Zhao David , McClain Donald , Kitzman Dalane W , Cheng Che Ping
Published: April 2024

Background:
Recent evidence showed that CaMKII inhibition with KN93 protects against diabetic cardiomyopathy (DCM). However, the off-target effects have limited its use. There are no CaMKII inhibitors available clinically. It may be best to use some complementary approaches for CaMKII inhibition. Previously we showed that diabetes produced upregulation of cardiac β
3
-AR-mediated inhibitory pathway promoting DCM progression. There is a significant crosstalk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β
3
-AR signaling in DCM. It is possible that the benefit of β
3
-AR antagonists (β
3
ANT) might involve modulation of CaMKII. We tested the hypothesis that chronic L-748-337, a selective β
3
ANT may inhibit CaMKII activity and limit DCM.

Methods:
LV myocyte CaMKIIδ expression and activity and myocyte function were determined in 3 groups (7/group) wild-type female mice over 14 weeks (W):
Type 2 DM
(
T2
), 14 W fed high-fat diet (HFD), but after HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. 5 days);
T2β

3

ANT
, T2 mice at 10 W received L-748,337 (10
-7
M/kg/day, mini-pump) for 4 W; and
Vehicle controls
(C).

Results:
Versus C, T2 diabetes was induced in mice received HFD and low dose STZ with significantly elevated blood glucose. But only T2 myocytes had significantly increased protein levels of CaMKIIδ (T2: 29%, 0.53 vs C: 0.41) and CaMKIIδ phosphorylation (at Thr287) (PCaMKIIδ) (79%, 0.52 vs 0.29) followed by significantly reduced cell contraction (dL/dt
max
, 75 vs 134 μm/s), relaxation (dR/dt
max
, 60 vs 114 μ m/s) and [Ca
2+
]
iT
(0.16 vs 0.21). The isoproterenol (ISO, 10
-8
M)-stimulated increases in dL/dt
max
(38% vs 58%), dR/dt
max
and [Ca
2+
]
iT
(19% vs 30%) were also significantly reduced. By contrary, versus C, T2β
3
ANT myocytes had similar levels of CaMKIIδ (0.37) and PCaMKIIδ (0.31) with preserved cell contractility (131 μm/s), relaxation (109 μm/s) and [Ca
2+
]
iT
(0.21). ISO caused increases in dL/dt
max
(57%), dR/dt
max
(52%) and [Ca
2+
]
iT
(30%) were also closed to control values.

Conclusions:
Chronic β
3
ANT prevents Type II diabetes-caused upregulation of cardiac CaMKIIδ, thereby leading to the preservation of normal myocyte function, [Ca
2+
]
iT
, and β-adrenergic reserve in a DCM murine model.
Abstract 9026: Endogenous Ca2+/Calmodulin-Dependent Protein Kinase II Overactivation Exacerbates Cardiac Dysfunction and Beta-Adrenergic Desensitization in a Mouse Model With Type 2 Diabetes
Authors: Cao Jing , Sun Xiaoqiang , Liu Yixi , Chen Zhe , Li Tiankai , Herrington David M , Kitzman Dalane W , Zhao David , Cheng Che Ping , Cheng Heng
Published: April 2024

Background:
Emergent evidence indicates that CaMKII overactivity in diabetes (DM) plays a crucial role in the pathophysiology of diabetic cardiomyopathy (DCM) by targeting a diverse array of proteins involved in cardiac electrical, structural and functional remodeling. CaMKII has been proposed to be a therapeutic target for DCM. However, although chronic inhibition of CaMKII has been associated with cardioprotection in several cardiovascular diseases, the direct cardiac effects of CaMKII activation in type 2 (T2) DM are unclear. Moreover, whether and how DCM alters cardiac responses to CaMKII are undefined. We tested the hypothesis that in DCM, CaMKII is upregulated, which alters cardiac contractile behavior. Endogenous CaMKII activation may produce direct depressions in LV myocyte basal function and β-adrenergic reserve. Acute inactivation of CaMKII with KN93 would have a beneficial impact in DCM.

Methods:
LV myocyte CaMKIIδ expression and activity and myocyte functional responses were compared in 2 groups (n=9/group) of wild-type female mice:
Vehicle Control (C)
, animals fed chow for 14 weeks (W);
T2DM,
i
nduced with a high-fat diet (HFD) intake for 14 W, but after fed HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. for 5 days). In T2DM, we further assessed myocyte contractile and [Ca
2+
]
i
transient ([Ca
2+
]
iT
) responses with and without acute treatment of myocytes with KN93 (10
-6
M, 30 min).

Results:
Versus C, in T2DM myocytes, the CaMKIIδ protein levels (28%, 0.51 vs 0.40) and CaMKIIδ phosphorylation (79%, 0.52 vs 0.29) were significantly increased. These changes were followed by significantly reduced cell contraction (dL/dt
max
, 76.0 vs 137.3 μm/s), relaxation (dR/dt
max
, 61.7 vs 116.0 μm/s) and [Ca
2+
]
iT
(0.16 vs 0.21). ISO-stimulated increases dL/dt
max
(39% vs 58%), dR/dt
max
(35% vs 54%) and [Ca
2+
]
iT
(20% vs 30%) were also significantly reduced. Moreover, in T2DM myocytes, superfusion with KN93 significantly improved myocyte basal contraction (104.2 μm/s), relaxation (79.3 μm/s) and [Ca
2+
]
iT
(0.21).

Conclusions:
In T2 diabetes-induced DCM, upregulation of CaMKIIδ has adverse functional effects. Acute endogenous CaMKII activation exacerbates LV myocyte dysfunction. The inhibition of CaMKII has a significant beneficial impact.
Abstract 9035: Scavenger Receptor-BI: Implications in Lipoprotein(a) Metabolism
Authors: Kindy Mark S
Published: April 2024

Introduction:
Lipoprotein(a) [Lp(a)] is a unique lipoprotein that has emerged as an independent risk factor for developing vascular disease and stroke.

Hypothesis:
We hypothesize that SR-BI is critical to the regulation of Lp(a) metabolism and that mutations in SR-BI contribute to the pathogenesis of CVD and stroke in relationship to Lp(a).

Methods:
Transgenic mice carrying the human Lp(a) [hLp(a)] on the SR-BI (mSR-BI) deficient mouse background, Lp(a) transgenic mice on the human SR-BI (hSR-BI) with and without the mSR-BI, and Lp(a) transgenic mice on the mutant hSR-BI with and without mSR-BI were used to determine the impact on Lp(a) catabolism and atherosclerosis.

Results:
We determined the levels of Lp(a) in wildtype and SR-BI KO mice, lipid levels and profiles and oxidized state of the Lp(a). In addition, studies on the impact of SR-BI and Lp(a) on atherosclerosis were examined. We showed that Lp(a) was elevated in SR-BI deficient mice and Lp(a) was reduced in hSR-BI tg mice, compared to wildtype SR-BI mice. Lp(a) mice with the mutant hSR-BI protein, showed significantly elevated Lp(a) levels. When Lp(a) levels were increased, Lp(a) was highly oxidized, lipid profiles were altered and mice develop significant atherosclerosis. We also showed that Lp(a) mice showed a higher incidence of hemorrhagic strokes and had worse outcomes following ischemic strokes.

Conclusions:
These studies will lay the ground work for both basic and translational studies to understand the impact of Lp(a) in CVD and stroke.
Abstract 9046: Effects of Acute Doses of Cocaine on Arterial Left Ventricular Coupling and Left Ventricular Mechanical Efficiency in Conscious, Chronically-Instrumented Dogs
Authors: Cheng Che Ping , Zhang Xiaowei , Li Tiankai , Zhang Zhi , Sun Xiaoqiang , Cao Jing , Herrington David M , Zhao David , Cheng Heng
Published: April 2024

Background:
Cocaine, one of the most commonly used illegal drugs, exaggerates sympathetic nervous activity and has profound effects on the cardiovascular system. It is well known that acute doses of cocaine raise the heart rate, and cause acute hypertension, arrhythmia, and reduce coronary blood flow. However, its role and mechanism on the arterial-left ventricular (LV) coupling (ALVC) and LV mechanical efficiency remain to be critically examined. We hypothesized cocaine may impair ALVC and produce myocardial contractile and metabolic abnormalities, and thus impair LV ability to convert metabolic energy to external work.

Methods:
We examined the effect of cocaine (4 mg/kg/iv) on ALVC and the conversion of metabolic energy [measured as myocardial oxygen consumption (MVO
2
)] to mechanical work [measured as pressure (P)-volume (V) area (PVA)], and PVA to external work (SW) in 6 conscious chronically instrumented dogs. The control MVO
2
-PVA relation was generated by altering loading conditions using three graded doses of Phenylephrine after autonomic blockade with hexamethonium and atropine.

Results:
Ten minutes after cocaine administration, blood cocaine level was 7.3±2.4 mg/L. There were significant decreases in the slope (E
ES
) of LV end-systolic P-V relation (5.0±0.09 vs 6.7±1.4 mmHg/ml, p<0.05), SW (1379±284 vs 1739±204 mmHg•ml, p<0.05) and increases in arterial elastance (E
A
) (13.6±2.6 vs 7.6±1.8 mmHg•ml, p<0.05). Despite the decrease in E
ES
, energy utilization as calculated from LV MVO
2
was increased (0.13±0.01 vs 0.10±0.02 ml O
2
/beat/100g LV, p<0.01) and the MVO
2
-PVA point was shifted above the control MVO
2
-PVA relation by 0.010±0.002 ml O
2
/beat/100g LV, (p<0.05). The SW/PVA ratio decreased (56±8% vs 75±12%, p<0.05) as impaired arterial-LV coupling indicated by a significantly increased the ratio of E
A
to E
ES
(from 1.2±0.4 of baseline to 2.8±0.05 after cocaine (p<0.05). Thus, SW/MVO
2
, representing LV mechanical efficiency, decreased from 11.0±1.9 to 8.8±1.2% (p<0.05) with cocaine.

Conclusions:
Acute doses of cocaine impair arterial LV coupling and decrease LV mechanical efficiency due to the decreased conversion of mechanical energy (PVA) to external work (SW) which mainly resulted from the deterioration of arteria-LV coupling.
Abstract 9053: ASIC3 Knockout Alleviates Exaggerated Blood Pressure Response Induced by P2X3 Activation in Hindlimb Muscle Afferent Nerves of Rats With Experimental Peripheral Artery Disease
Authors: Qin Lu , Li Qin , Li Jianhua
Published: April 2024

Background:
In peripheral artery disease (PAD), the metaboreceptor and mechanoreceptor in muscle afferent nerves contribute to accentuated sympathetic outflow via a neural reflex. Particularly, lactic acid and ATP produced in exercising muscles respectively stimulate acid sensing ion channel subtype 3 (ASIC3) and purinergic subunit P2X3 receptors in muscle afferent nerves, inducing the reflex sympathetic and arterial blood pressure responses during exercise.

Methods:
We examined that the P2X3 protein expression in the dorsal root ganglion (DRG) and P2X currents in DRG neurons using western blotting and patch-clamp methods, and the pressor response to P2X3 stimulation using the whole animal preparations. Four groups were included: 1. Wild type (WT) rats; 2. ASIC3 knockout (KO) rats; 3. WT-PAD rats with three days of femoral artery occlusion; 4. KO-PAD rats with three days of femoral artery occlusion.

Results:
First, P2X3 expression was significantly increased in KO rats compared with that in WT rats (optical density: 6.51±2.20/n=5;
P
<0.05
vs.
WT). However, the levels of P2X3 expression were not significantly increased in KO-PAD rats compared with the KO rats (optical density: 7.99±1.99/n=6;
P
>0.05
vs.
KO) . Second, in WT rats, as 10, 30 and 50 μM of αβ-me ATP (P2X3 agonist) were applied, peak amplitude of both transient and sustained P2X currents was increased by femoral artery occlusion (all
P
<0.05 WT-PAD
vs.
WT). Insignificant differences in both transient and sustained P2X currents were found between KO rats and KO-PAD rats (all
P
>0.05
vs.
KO) when αβ-me ATP was applied except of the transient P2X current amplitude at 50 μM of αβ-me ATP. Third, there were insignificant differences in the mean arterial pressure response to 0.0625, 0.125 and 0.25 mM of αβ-me ATP injected into the hindlimb circulation between KO rats and KO-PAD rats (all
P
>0.05
vs.
KO).

Conclusions:
Compared with WT rats, augmented P2X3-mediated pressor response is blunted by ASIC3 KO in PAD rats and this is accompanied with downregulated P2X3 expression and suppressed activities in P2X3 signaling pathways in muscle afferent neurons.
Abstract 9062: A Rapid and Point-of-Care Device for Real-Time Monitoring of Pulmonary Hypertension Biomarkers
Authors: Noushin Tanzila , Tabassum Shawana
Published: April 2024

Introduction:
Pulmonary hypertension (PH) is a life-threatening condition that remains undetected at an early stage because diagnosis relies heavily on physiological presentations. The gold standard for biomolecular analysis is a blood test, which is invasive and increases the risk of infections, particularly in rural areas. To narrow this gap, we used a low-cost fabrication method to develop a sensor for real-time and bedside monitoring of a PH biomarker, B-type natriuretic peptide (BNP) in serum.

Hypothesis:
The sensor will facilitate research on early identification of the risk of PH from dynamic measurements of biomarkers, which will reduce cardiac failures resulting from delayed and missed diagnoses of PH

Methods:
We used a low-cost screen-printing technique to fabricate a 3 electrode-based electrochemical sensor on a flexible polyimide substrate (Fig. 1a). The working electrode (WE) was functionalized with anti-BNP. The sensor was interfaced with a potentiostat that applied a potential between the WE and reference electrode (RE) and measured the resulting current from the WE to counter electrode (CE). The BNP/anti-BNP binding on the WE resulted in variations in the redox current.

Results:
The sensor detected BNP in only 50 μl of fetal bovine serum. Fig. 1b shows the current vs. potential scan for BNP concentrations ranging from 0.1 to 500 pg/mL. The amount of current flow between WE and CE was proportional to the serum BNP levels. The sensor exhibited a sensitivity of 0.584 μA (pg/mL)
-1
cm
2
(from Fig. 1c) and a response time of 4s. The sensor also showed high selectivity against common interfering species (Fig. 1d) and good repeatability with a response variability of <1% between identical sensors (Fig. 1e).

Conclusions:
The project will advance the field of bedside monitoring of PH biomarkers. The low-cost and plug-and-play feature of the sensor allows adoption by rural communities. The sensor can be readily reconfigured and expanded to monitor other biomarkers.
Abstract 9081: Fatal Occlusive Pulmonary Vasculopathy in Rats Late After Perinatal Hypoxia: Hyperproliferative and Pro-Inflammatory Phenotypes and Related Differential Dna Methylation in Cultured Pulmonary Arterial Smooth Muscle Cells as the Potential Substrate
Authors: Oshita Hironori , Sawada Hirofumi , Mitani Yoshihide , TSUBOYA NAOKI , Kabwe Jane , Maruyama Junko , Yusuf Ali , Ito Hiromasa , Okamoto Ryuji , Yodoya Noriko , Otsuki Shoichiro , Ohashi Hiroyuki , Oya Kazunobu , Kobayashi Yuhko , Kobayashi Issei , Dohi Kaoru , Nishimura Yuhei , Saitoh Shinji , hirofumi sawada , Hirayama Masahiro
Published: April 2024

Background:
Perinatal insults increase the risk of developing various adult-onset vascular diseases. Although we recently established a fatal SU5416/hypoxia-induced model with worsening pulmonary vascular disease (PVD) in rats late after exposure to perinatal hypoxia, the mechanisms are elusive.

Hypothesis:
In rats with fatal occlusive PVD late after perinatal hypoxia, cultured pulmonary arterial smooth muscle cells (PASMCs) from rats before SU5416/hypoxia treatment exhibit phenotypic and epigenetic changes.

Methods:
PVD was induced in 7-week-old rats exposed to perinatal hypoxia or ambient air by injecting SU5416 followed by exposure to hypoxia for 3 weeks (SU5416/hypoxia). Rats were assessed at the baseline (7 weeks of age) and 8 weeks after SU5416 injection (15 weeks of age). Proliferation, cytokine production and genome-wide DNA methylation profile were evaluated in PASMC isolated from the baseline rats with/without perinatal hypoxia.

Results:
In SU5416/hypoxia rats, perinatal hypoxia reduced body weight gain and survival, and increased right ventricular systolic pressure, Fulton index and occlusive PVD (p<.05), which were associated with an increase in perivascular macrophages, expression of prepro-endothelin-1 mRNA and eNOS protein in the lung (p<.05) but not with impaired alveolarization or worsening right ventricular fibrosis. In PASMCs isolated from the baseline rats, perinatal hypoxia enhanced PDGF-BB-induced cell proliferation and phosphorylation of extracellular signal-regulated kinase as well as TNFα-induced expression of IL-6, monocyte chemotactic protein 1 and phosphorylation of p38 (p<.05). DNA methylation profiling identified 35 differentially methylated regions (DMRs). Methylation in the region encoding phosducin like protein (Pdcl) was associated with decreased PDGF-BB-induced expression of
Pdcl
mRNA in PASMCs with perinatal hypoxia. Functional enrichment analysis of DMRs revealed the relation to cell proliferation and inflammatory process (ie, Wnt5A and ROR1).

Conclusions:
In SU5416/hypoxia rats late after perinatal hypoxia, hyperproliferative and pro-inflammatory phenotypes and functionally related differential DNA methylation in PASMCs may be the substrate for the fatal occlusive PVD.
Abstract 9099: Echocardiographic Score versus Conventional Clinical Risk Score to Predict Thromboembolic Events at Younger Ages or First Thromboembolic Events in Patients with Non-valvular Atrial Fibrillation in Japan: The Fushimi AF Registry
Authors: Tezuka Yuji , DOI KOSUKE , Hamatani Yasuhiro , ISHII MITSURU , Iguchi Moritake , Masunaga Nobutoyo , Esato Masahiro , Wada Hiromichi , Hasegawa Koji , Ogawa Hisashi , Abe Mitsuru , Akao Masaharu
Published: April 2024

Introduction:
In patients with atrial fibrillation (AF), age and history of stroke are the strongest risk factors of thromboembolism events (TE). However, in patients with AF, especially in those with younger age or without previous TEs, preventing TEs is of clinical importance. We reported that echocardiographic (Echo) parameters such as enlarged left atrial diameter (LAD) or increased relative wall thickness (RWT) of left ventricle (LV) or smaller LV end-diastolic diameter (LVDd) were associated with incidence of TEs. We assessed whether the score based on Echo parameters (Echo score) can discriminate TEs, and compared its performance with a conventional clinical risk score.

Methods:
In the Fushimi AF Registry, follow-up data were available for 4,472 patients. Of them, Echo data at enrollment were available for 3,246 patients with non-valvular AF (NVAF). We investigated the relationship between Echo score [RWT ≥0.409, LVDd <50 mm, LAD >45 mm, each 1 point] and incidence of ischemic stroke (IS)/systemic embolism (SE) during 3 year follow-up in all patients, and patients with younger age and without previous stroke/SE, respectively.

Results:
During the median follow-up period of 1,095 days, 149 IS/SE events occurred. The incidence of IS/SE according to the groups stratified by Echo score is shown (Figure). Even in those with younger age or without previous stroke/SE, Echo score nicely discriminated the risk of TEs and the c-statistic was higher than that of CHA
2
DS
2
-VASc score (Table).

Conclusions:
Echo score better discriminated TEs in NVAF patients even with younger age or without previous TEs, than CHA
2
DS
2
-VASc score. Further research is needed to generalize the result.
Abstract 9103: Electrophysiological Arrhythmia Characterization of a Stress-Induced Idiopathic VF IPS-CMs Using Fluorescent Optical Mapping
Authors: Kalluri Manasa , Lang Di , Anderson Corey , Glukhov Alexey , Eckhardt Lee L , Reilly Louise
Published: April 2024

Background:
Idiopathic ventricular fibrillation (IVF) is a clinically challenging disease entity as phenotypic characteristics are lacking. We studied induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) from a patient with stress-induced IVF to define the cellular arrhythmic behavior and create a path to test therapeutics.

Methods:
iPS-CMs were generated from control (WT) and stress-induced IVF (si-IVF) patient-specific iPSC lines. Cells were characterized by single-cell optical mapping using calcium sensitive dye (Fluo-4) and electrical pacing (0.5Hz), with β-adrenergic stimulation (1x10
-6
mM isoproterenol (ISO)).

Results:
si-IVF cells had longer CaT rise time (ms) at baseline (BSL) (p<0.05) (86 +/- 5.45, n=54) and after ISO (83.88 +/- 5.12, n=41) than WT cells (BSL: 64.5 +/- 3.72, n=40) (ISO: 72 +/- 9.92, n=10). si-IVF cells had shorter CaT duration (ms) at BSL (1,069 +/- 36.00, n=54) than WT cells at BSL (1,280 +/- 37.59, n=40), with no significant difference after ISO (IVF: 1,073 +/- 44.51, n= 41 and WT: 1,230 +/- 32.79, n=10). Following ISO, 11.5% of si-IVF cells showed arrhythmic behavior with rapid continuous spontaneous Ca
2+
release (Fig. 1), compared to 0.0% of WT cells.

Conclusion:
We demonstrate feasibility of differentiating iPS-CMs from patients while investigating arrhythmogenicity of si-IVF cells compared to controls using optical mapping. Insights from CaT duration, rise time, and arrhythmogenic behavior helps establish the arrhythmogenic behavior, and begins to provide mechanistic insights into si-IVF. This methodology can be applied to test therapeutics for IVF patients with β-adrenergic triggers.
Figure 1:
Patient #1-specific si-IVF iPS-CM.
A)
Representative optical mapping recordings of iPS-CMs baseline paced at 1Hz (each trace is a separate cell)
B)
Application of ISO caused arrhythmic behavior and failure to capture paced beats in black, red, blue, and yellow traces but retention of paced response in green and grey traces.
Abstract 9112: Dexmedetomidine Reduces Incidences of Ventricular Arrhythmias in Adults
Authors: Zhong Qiaonan , Kumar Ashish , Deshmukh Abhishek , Bennett Courtney
Published: April 2024

Introduction:
Ventricular arrhythmias, including ventricular tachycardia (VT) and ventricular fibrillation (VF), are associated with high mortality and morbidity. Sedation through agents like benzodiazepines, propofol, and opiates are mainstays of treatment but are limited by side effects. Dexmedetomidine is a α2-presynaptic receptor agonist with a safe and efficacious sedative profile. Furthermore, it has been recently proposed as a sedative agent in VT due its additional antiarrhythmic properties.

Methods:
A systemic literature review was conducted of MEDLINE, EMBASE, Cochrane, and Scopus. Randomized controlled trials comparing the incidence of ventricular arrhythmias of dexmedetomidine with placebo or an alternative sedative agent were included. Two researchers independently extracted the data and performed quality assessments.

Results:
We identified 6 studies that met the selection criteria. Our meta-analysis demonstrated significant reduction of the overall risk of ventricular arrhythmias in patients receiving dexmedetomidine (RR 0.35, 95% CI 0.16, 0.76). Furthermore, there was no significant difference in risk of mortality (RR 0.59 95% CI 0.12, 3.02). Dexmedetomidine also significantly increased the risk of bradycardia (RR 2.78 95% CI 2.00, 3.87). There was no significant difference in risk of tachycardia (RR 0.59 95% CI 0.12, 3.02) or hypotension (RR 1.07 95% CI 0.64, 1.81).

Conclusions:
Our study demonstrates that the dexmedetomidine reduces the risk of VA by 65% compared to control. Further prospective research is necessary to clarify the antiarrhythmic and sedative properties of dexmedetomidine and its potential effect on patient outcomes.
Abstract 9126: Renal Venous Stasis Index Reflects Renal Congestion and Predicts Adverse Outcomes in Patients With Heart Failure
Authors: Ohara Himika , Yoshihisa Akiomi , Sugawara Yukiko , Ichijo Yasuhiro , Hotsuki Yu , Watanabe Koichiro , Sato Yu , Kimishima Yusuke , Misaka Tomofumi , Oikawa Masayoshi , KOBAYASHI ATSUSHI , Takeishi Yasuchika
Published: April 2024

Background:
It has been recently reported that the renal venous stasis index (RVSI) assessed by renal Doppler ultrasonography provides information to stratify pulmonary hypertension (PH) leading to right-sided heart failure. However, the clinical significance of RVSI on heart failure (HF) patients has not been fully examined. We aimed to clarify the associations of RVSI with parameters of cardiac function and right heart catheterization (RHC), as well as with prognosis, in patients with HF.

Methods:
We performed renal Doppler ultrasonography, echocardiography and RHC in hospitalized patients with HF (n = 388). The RVSI was calculated as follows: RVSI = (cardiac cycle time - venous flow time)/cardiac cycle time. These patients were divided into three groups based on RVSI: RVSI 0 group (RVSI = 0, n = 260, 67%), low RVSI group (0 < RVSI ≤ 0.21, n = 65, 17%) and high RVSI group (RVSI > 0.21, n = 63, 16%). We examined associations between RVSI and parameters of cardiac function and RHC, and followed up for cardiac events such as cardiac death and worsening HF.

Results:
There were significant correlations between RVSI and right atrial pressure (R = 0.253, P <0.001), right atrial end-systolic area (R = 0.327, P <0.001) and inferior vena cava diameter (R=0.327, P <0.001), but not with cardiac index (R = -0.019, P = 0.769). During the follow-up periods (median 412 days), cardiac events occurred in 60 patients. In the Kaplan-Meier analysis, accumulated cardiac event rate increased with advancing RVSI (Figure, log-rank, P = 0.001). In the multivariable Cox proportional hazard analysis, cardiac event rate was independently associated with RVSI (hazard ratio, 1.874; 95% confidence interval, 1.023-3.435, P = 0.042).

Conclusion:
RVSI assessed by renal Doppler ultrasonography reflects right-sided overload and is associated with adverse prognosis in HF patients.
Abstract 9139: Two Decade Trends in Cardiovascular Health Among Adults With Cardiovascular Disease in the United States Using a Revised American Heart Association Life's Simple 7 Framework
Authors: Gao Yumin , Isakadze Nino , Duffy Eamon , Sheng Qicong , Ding Jie , MacFarlane Zane , McClure Scott T , Sang Yingying , Selvin Elizabeth , Matsushita Kuni , Martin Seth S
Published: April 2024

Introduction:
The American Heart Association Life’s Simple 7 (LS7) framework is used to promote cardiovascular health. Trends in cardiovascular health of US adults with a history of cardiovascular disease (CVD) are not well characterized.

Hypothesis:
To assess trends in LS7 factors in US adults with CVD.

Methods:
In 4,233 adults with a self-reported history of CVD (i.e., myocardial infarction, stroke, angina, and heart failure) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, we constructed a revised 14-point LS7 score. The revision included Healthy Eating Index-2015 for scoring diet, non-HDL-cholesterol for cholesterol, hemoglobin A1c and self-reported diabetes for blood glucose, blood pressure cutoffs that reflect current guidelines for adults with CVD, and removal of medication use in scoring cardiovascular health (Figure). We used multivariable linear regression to examine trends in cardiovascular health, accounting for weights and the complex survey design.

Results:
After adjusting for age, sex, and race/ethnicity, the mean revised LS7 score in US adults with CVD remained low from 5.72 in 1999-2002 to 5.80 in 2015-2018 (p-for-trend=0.084) (Figure). Improvements were noted in cholesterol control (7.0% achieving ideal in 1999-2002 to 28.9% in 2015-2018, p-for-trend <0.001) and smoking cessation (32.8% ideal in 1999-2002 to 37.9% in 2015-2018, p-for-trend=0.037). There were declines in blood glucose and weight control (65.6% and 24.2% ideal in 1999-2002 to 52.6% and 14.7% in 2015-2018, p-for-trends <0.001). Proportions achieving ideal remained low and unchanged for diet and physical activity (1.4% and 2.8% in 1999-2002 to 0.7% and 3.9% in 2015-2018, p-for-trend=0.61 and 0.41).

Conclusions:
Over the last two decades in US adults with CVD, among LS7 factors, cholesterol and smoking improved, while glucose and weight worsened, with an overall concerning trend of persistently suboptimal cardiovascular health.
Abstract 9142: Predictors of New-Onset Atrial Fibrillation in the Setting of Acute Coronary Syndromes: A Nationwide Multi-Center Study
Authors: Ne Jia Yi Anna , Ng Austin Chin Chwan , HYUN Karice , Boroumand Farzaneh , Chow Clara K , Freedman Ben B , Brieger David
Published: April 2024

Introduction:
New-onset atrial fibrillation (AF) following acute myocardial infarction (AMI) is associated with adverse outcomes, though studies exploring the interaction between AF and the full spectrum of acute coronary syndromes (ACS) are scarce. We aim to identify predictors of new-onset AF in the setting of ACS by analyzing data from the prospective CONCORDANCE multi-center registry.

Methods:
Patients admitted to 41 Australian hospitals from 2009-2018 with ACS and had an angiogram were included. New-onset AF was defined as AF detected on index ECG and/or in-hospital AF. Independent predictors of new-onset AF were identified using multivariable logistic regression models.

Results:
Of 9070 consecutive patients admitted with ACS, 648 (7.1%) patients developed new-onset AF. These patients had higher rates of major adverse in-hospital events and all-cause mortality compared to patients without new-onset AF. Age (adjusted odds ratio [aOR] 1.04, 95% confidence interval [CI] 1.03-1.05), male sex (aOR 1.62, 95%CI 1.29-2.04), higher admission heart rate (aOR 1.02, 95%CI 1.01-1.02), cardiac arrest on admission (aOR 1.98, 95%CI 1.23-3.20), Killip classes 2 (aOR 1.38, 95%CI 1.10-1.73) and 3/4 (aOR 1.72, 95%CI 1.24-2.40) versus 1 were independent predictors of new-onset AF, whereas hypertension (aOR 0.81, 95%CI 0.67-0.99), higher minimum hemoglobin (aOR 0.98, 95%CI 0.97-0.98), pre-admission statins (aOR 0.71, 95%CI 0.56-0.89) and undergoing PCI (aOR 0.64, 95%CI 0.53-0.77) were associated with decreased risk of new-onset AF. When angiographic disease burden was included, double and triple-vessel disease were independent predictors of new-onset AF. However, sequential addition of CABG to the model nullified this association; (CABG (aOR 3.94, 95%CI 2.83-5.49), disease burden non-significant). In the CABG subgroup, peripheral arterial disease (aOR 1.98, 95%CI 1.20-3.27) was an independent predictor of new-onset AF (all p<0.05).

Conclusions:
This present study identified patients at risk of new-onset AF in the setting of ACS. Such patients could be targeted for increased surveillance for AF and related adverse outcomes during the post-infarct period. In addition, future studies should explore strategies to prevent new-onset AF after ACS.
Abstract 9163: Demographic Differences in Hypertension and Its Treatment in Malawi
Authors: Shakil Saate S , Price Alison J , Roth Gregory A , Crampin Amelia , Nkoka Owen , Kanjala Chifundo
Published: April 2024

Background:
Hypertension (HTN), a strong risk factor for cardiovascular disease (CVD), is highly prevalent in Sub-Saharan Africa. Health system interventions targeting demographic determinants of diagnosis and treatment may reduce downstream CVD burden. We investigated age, sex, and location-specific differences in HTN diagnosis and treatment in Malawi.

Methods:
We examined population-based household survey data (2013 - 2017) from the Malawi Epidemiology and Intervention Research Unit of 30,575 adults
>
18 years with self-reported HTN diagnosis/treatment status and resting blood pressure measurements using standardized protocols. We used logistic regression to explore associations between demographic variables (age, sex, rural/urban location) and two outcomes: (1) measured HTN (defined as SBP
>
130 mmHg, regardless of diagnosis/treatment status), and (2) treatment for previously diagnosed HTN.

Results:
The overall prevalence of diagnosed and undiagnosed HTN was 9% and 19.6%, respectively; 45.4% of those previously diagnosed were on antihypertensive treatment. The probability of measured HTN regardless of treatment for those aged >65 years was 80.8% (95% CI 79.1 - 82.5) and 66.5% (64.0 - 68.9) for urban women and men, respectively, and 65.6% (63.5 - 67.7) and 52.2% (49.7 - 54.7) for rural women and men, respectively. Among those with previously diagnosed HTN, probability of treatment was higher in older age groups, but did not differ between locations.

Conclusions:
We observed a high prevalence of undiagnosed HTN among rural- and urban-dwelling Malawians; over half of those reporting a diagnosis were untreated. Probability of measured HTN varied by sex and location, but probability of treatment did not. Population-level interventions that account for these patterns are needed in both rural and urban settings to increase effective HTN treatment coverage.
Abstract 9165: Relationship Between the Cholesterol and Triglyceride Content of Lipoprotein Subclasses and Carotid Imtima-Media Thickness: Results from the Kyushu and Okinawa Population Study
Authors: Ikezaki Hiroaki , Furusyo Norihiro , Ai Masumi , Okazaki Mitsuyo , HAYASHI JUN , Polisecki Eliana J
Published: April 2024

Introduction:
The association between 20 lipoprotein cholesterol and triglycerides subclasses and carotid intimal medial thickness (cIMT) progression has not been evaluated fully.

Objective:
Our goal was to assess which lipoprotein subclasses were associated with max cIMT levels.

Methods:
Levels of cIMT and 20 lipoprotein cholesterol and triglycerides subclasses using gel permeation high-performance liquid chromatography (GP-HPLC) were analyzed in 864 men and women (mean age 57 years, free of chronic liver or kidney diseases and off cholesterol-lowering, hormone replacement, or adrenocorticosteroid medications). Univariate and multivariate regression analyses were performed to examine the relationships between lipoprotein subclasses and max cIMT levels.

Results:
Max cIMT levels were 0.90 mm in women and 0.97 mm in men. After adjustment for age, gender, systolic blood pressure, smoking habits, diabetes, and hypertension treatment, elevated low-density lipoprotein cholesterol-2 and -3 were associated with higher max cIMT levels in both women and men. Decreased high-density lipoprotein cholesterol-7 were associated with higher max cIMT levels only in women (all
P
for trend < 0.05). However, no associations were found between any triglyceride subclasses and max cIMT levels.

Conclusions:
Our data indicate that elevated smaller LDL cholesterol levels separated by GP-HPLC were significantly associated with max cIMT in both men and women. Our results support the concept that small dense LDL cholesterol is the most atherogenic lipoprotein parameter.