bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11929: Simultaneous Assessment of Myocardial Viability With
18
F-fluorodeoxyglucose Uptake and Late Gadolinium Enhancement by PET/MRI
Authors: Masuda Atsuro , Yamaki Takayoshi , Kunii Hiroyuki , Nanbu Takeyuki , Hara Takamitsu , Kubo Hitoshi , Ito Hiroshi , Takenoshita Seiichi , Takeishi Yasuchika
Published: April 2024

Introduction:
Both
18
F-fluorodeoxyglucose (FDG) PET and late gadolinium enhancement on cardiac MRI (LGE-CMR) have been utilized for myocardial viability evaluation. However, the association between these 2 modalities has not been fully investigated. The aim of this study was to compare FDG PET and LGE-MRI findings simultaneously using an integrated PET/MRI.

Methods:
Twelve participants (age 68.8 ± 7.9 years old, 11 males, left ventricular ejection fraction 40.5 ± 15.0%) with old myocardial infarction were enrolled. Total 204 segments were analyzed according to the 17-segment model. FDG PET/MRI was performed for each participant under hyperinsulinaemic-euglycemic state. The FDG uptake was semiquantitatively measured as %uptake. The transmural extent of LGE-CMR was evaluated by a 5-point scoring system (0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4 = 76-100%). Left ventricular (LV) wall thickness at end-diastolic phase and LV wall thickening were also measured by CMR. Viable myocardium was defined as less than 50% of the transmural extent of LGE-CMR.

Results:
Relative FDG uptake and the transmural extent of LGE-CMR were significantly correlated (P < 0.0001, Spearman ρ = -0.63). Relative FDG uptake was correlated with LV wall thickness (P = 0.003, ρ = 0.22) and LV wall thickening (P < 0.0001, ρ = 0.59). Receiver operating characteristic analysis demonstrated that the best cut-off value of FDG uptake to predict myocardial viability was 63% (area under the curve 0.90). When the cut-off value set to 63%, sensitivity was 81.6%, specificity was 80.8%, and accuracy was 81.4%.

Conclusions:
Relative FDG uptake was comparable to the transmural extent of LGE-CMR in assessing myocardial viability. Simultaneous evaluation using the integrated PET/MRI is feasible and may provide novel insights into evaluation of the myocardial viability.
Abstract 12022: LinkCPR Improves the Quality of Hands-only CPR Performed by Laypersons Following the 2015 AHA Guidelines
Authors: Yang Zhengfei , Chen Jinwu , Yu Tao , Peberdy Mary Ann , Ornato Joseph P , Tang Wanchun
Published: April 2024

Introduction:
The AHA 2015 Resuscitation Guidelines changed the guidelines for chest compression (CC) rate and depth. Manikin studies have demonstrated that feedback/prompt systems improve the quality of CPR. On the other hand, LinkCPR (SunLife, China) is a newly designed feedback/promt device that can provide the real-time CC depth, rate, chest recoil feedback and data review. In this study, we investigated the effects of LinkCPR on the quality of CCs during hands-only CPR performed by laypersons based on the 2015 AHA guidelines.

Hypothesis:
LinkCPR improves the quality of CCs performed by laypersons.

Methods:
Eighty laypersons were assigned randomly to perform CPR on manikins with (Link group) or without (C group) LinkCPR. Participants underwent manual CPR training and took a written basic life support examination; they were then required to perform two min of hands-only CPR. The quality of CPR was quantified as the percentage of correct CCs (appropriate depth, rate, and complete recoil) each minute.

Results:
Thirty-nine participants in the Link group and 37 participants in the C group completed the study. There were no significant differences in gender and body mass index between groups. Reductions in the mean depth of CCs and proportion of correct CCs after the first minute of CPR were observed in both groups. However, significantly better performance was achieved by rescuers in the Link group when compared with those in C group during each of the 2 minute CPR periods (Table).

Conclusion:
LinkCPR improves the quality of hands-only CPR performed by laypersons following the standards of the 2015 AHA guidelines.
Abstract 12023: The Effectiveness Teaching Continuous Chest Compression CPR Using a Combined Program of Watching a Brief Video, Seeing a Live CPR Demonstration Performed on a Mannequin and Using the Celtic Cell Phone Application for Real Time Feedback
Authors: Nayak Srishti , Nuno Tomas , Burns Whitney , Beskind Daniel L
Published: April 2024

Introduction:
CPR training via cell phone application is an effective way to train laypersons in CPR. However, it is unclear whether using a combination of watching a brief video and live demonstration of CPR as well as receiving real time feedback via a cell phone application improves CPR quality, responsiveness and confidence.

Objective:
To determine if viewing a brief chest compression only (CCO) CPR video, watching a live demonstration and receiving real time feedback via the Celtic cell phone app. is an effective modality in training laypersons CCO-CPR leading to improved performance, responsiveness, and confidence.

Methods:
This was a prospective cohort control analysis from June 2014 till January 2016. Participants had little or no previous CPR training. Participants were consented and filled out an 8-question survey regarding baseline confidence in performing CPR. A CPR content quiz was answered to determine fluency in CPR. All participants then performed CPR on a mannequin while receiving real time feedback via the Celtic cell phone app. Finally they received formal “verbal” and “visual” training on CCO-CPR. Compression rate was categorized as very good if their compressions per minute (cpm) were >90, Ok if CPM was 80-89 and poor if CPM was <80. Compression depth categories were: Excellent: >2.0 inches, Good: 1.5-2.0 inches and Poor: <1.5 inches.

Results:
There were statistically significant improvements in percentage of participants (N=67) with very good compression rates (OR=49.1; 95% CI: 17.8, 135.0) and excellent compression depth (OR=26.5; 95% CI: 7.3, 96.1) from before to after the training and feedback using the Celtic app. Average score for confidence questions (difference=4.34; 95% CI: 3.67, 5.00); willingness to perform CPR in cardiac arrest patients (OR=6.83; 95% CI: 2.75, 17.01); and percent of content knowledge (difference=30.2; 95% CI: 25.0, 35.4) were significantly improved.

Conclusions:
CCO-CPR training via a combined program of watching a brief CCO video and live demonstration as well as getting real-time feedback via the Celtic cell phone application demonstrated statistically significant improvements in both target compression rate and depth as well as confidence in laypersons attempting to perform CCO-CPR.
Abstract 12072: Damage to Coating Polymer Can Cause Serious Complications After Drug-Eluting Stent Implantation: A Pathological Study in Human Coronary Arteries
Authors: Inoue Katsumi , Imai Masao , Kimura Takeshi
Published: April 2024

Introduction:
Polymer coating is indispensable to optimize controlled drug release kinetics following drug-eluting stent (DES) implantation. However, how it can be damaged during the stenting procedure and the subsequent clinico-pathological events are not well studied.

Hypothesis:
We histopathologically assessed the hypothesis that damage to polymer coating can hinder DES efficacy.

Methods:
The study sample comprised 32 DES-implanted lesions obtained by autopsy from 2.5 to 49 months after stenting: 27 with durable polymers (Cypher, 12; Taxus, 6; Endeavor, 4; and Xience, 5) and 5 with biodegradable polymers coated only on the abluminal surface (Nobori, 3 and Ultimaster, 2). Tortuous lesions accounted for 60% and calcified lesions for 88%. We examined microscopically at least six slices from each lesion.

Results:
Polymer cracking or delamination was observed in about 6% of Cypher struts and 4% of Taxus struts. In two Cypher-implanted lesions with stent thrombosis occurring beyond one year after stent implantation, significant detachment of polymer fragments phagocytosed by giant cells was observed, and their arterial walls were aneurysmally dilated with extensive inflammatory infiltration of the intima, media, and adventitia, predominantly consisting of T cells, eosinophils, and considerable giant cells. In Xience-implanted lesions, polymer damage was little. In contrast, in most Endeavor-implanted lesions, large spallings of the polymer were found, and numerous phagocytosed polymer remnants scattered in the thickened neointima. In Nobori- or Ultimaster-implanted calcified lesions within 4 months after the procedure, remarkable detachment of polymer coating resulted in severe inflammatory reaction consisting of macrophages and lymphocytes.

Conclusions:
Polymer disruption may result in nonuniform drug distribution that may allow neointimal hyperplasia in the DES-implanted lesions. Moreover, polymer cracking may induce adverse and interrelated effects such as local inflammation and amplified cellular response, followed by very late stent thrombosis. Compared with polymer around the stent struts, delamination of abluminal polymer might occurr more easily when it is delivered through a calcified coronary artery.
Abstract 12101: Vectorcardiographic QRS and T Loop Roundness is Associated With Sudden Cardiac Death: The Atherosclerosis Risk in Communities and the Cardiovascular Health Study
Authors: Mai Tuan V , Kabir Muammar M , Sedeghat Golriz , Thomas Jason , Waks Jonathan W , Sitlani Colleen M , Biggs Mary L , Henrikson Charles A , Sotoodehnia Nona , Biering-Sørensen Tor , Siscovick David S , Post Wendy S , Soliman Elsayed Z , Solomon Scott , Buxton Alfred E , Josephson Mark E , Tereshchenko Larisa G
Published: April 2024

Introduction:
Vectorcardiography (VCG) analysis using QRS and T loop roundness has been shown to be associated with prior myocardial infarction, but their association with sudden cardiac death (SCD) remains unknown.

Hypothesis:
We hypothesized that QRS and T loop roundness are independently associated with sudden cardiac death (SCD).

Methods:
We prospectively analyzed reconstructed VCGs of 19,972 subjects at the baseline visit from the Cardiovascular Health Study (n=5374, age >65) and the Atherosclerosis Risk in Communities study (n=14,598, age 45-64). QRS and T loop roundness was measured by the roundness index (RI) and principal component analysis (PCA) ratio. We evaluated the association between these parameters and the risk of SCD using 3 multivariate Cox Models. Model 1 adjusted for demographic characteristics (age, sex, race, study center/cohort), model 2 additionally adjusted for prevalent cardiovascular disease (coronary heart disease, heart failure, stroke, atrial fibrillation, use of beta blocker) and traditional cardiovascular risk factors (BMI, hypertension, diabetes, smoking, alcohol, cholesterol, HDL, triglycerides, physical activity index, creatinine), and model 3 further adjusted for ECG parameters associated with SCD (heart rate, QRS QTc, sex-specific Cornell product, BBB/IVCD).

Results:
Smaller QRS loop RI (SD) was independently associated with SCD in model 3 (HR 0.89 [95%CI 0.81-0.97]; p=0.01). Larger T loop RI (SD) was associated with SCD only in minimally adjusted model 1 (HR 1.14 [95%CI 1.06-1.23]; p=0.01). Larger T loop PCA ratio (SD) was associated with SCD in all three models (model 1, HR 1.32 [95%CI 1.23-1.43]; model 2, HR 1.16 [95%CI 1.07-1.25]; model 3, HR 1.11 [95%CI 1.03-1.20], all p <0.01).

Conclusions:
Smaller QRS loop roundness and larger T loop roundness are associated with an increased risk of SCD. VCG analysis can help identify patients at increased risk of SCD.
Abstract 12190: Physiologic Dysregulation Experienced by Immigrants is Mitigated by Immigrating at a Younger Age and Family Reunification: The Africans in America Study
Authors: Bingham Brianna A , Duong Michelle T , Aldana Paola C , Ricks Madia , Mabundo Lilian S , Udahogora Margaret , Berrigan David , Sumner Anne E
Published: April 2024

Introduction:
Immigration from Africa to the United States is stressful. Stress causes cardiovascular (CV), metabolic and immune dysregulation. Allostatic load score (ALS) quantifies the effect of dysregulation in these 3 systems.

Objective:
Our goal was to determine the influence of age of immigration, reason for immigration and unhealthy assimilation behavior on ALS in 238 African immigrants (AI) (age 40±10, mean±SD, range 21-64y).

Methods:
ALS was calculated using 10 variables, 6 were CV (SBP, DBP, triglyceride, cholesterol, homocysteine), 4 were metabolic (BMI, A1C, albumin, eGFR) and 1 was immune (CRP). Each variable was divided into sex-specific quartiles. High risk was defined by the highest quartile for each variable except albumin and eGFR which were defined by the lowest quartile. Each biomarker was assigned 1 point if in the high risk quartile and 0 if not. Unhealthy assimilation behavior was defined by increases in smoking, alcohol intake and sedentary activity after living in the US for ≥10y.

Results:
At enrollment all AI were adults (≥18y). Overall, 16% of AI were childhood immigrants (arrived in US <18y); 84% were adulthood immigrants (arrived in US≥18y). Compared to adulthood AI, childhood AI were younger (30±7 vs. 42±9,
P
<.01) and lived in the US longer (20±8 vs. 12±9y,
P
<.01). Age-adjusted ALS were similar in childhood and adult AI (2.78±1.83 vs. 2.73±1.69,
P
=.87). In multiple regression analysis (adjR
2
=0.24), older age at immigration and more years in the US were associated with higher ALS. Whereas current age, education and income had no effect on ALS. Reasons for immigration were: family reunification, work, study, marriage, lottery and asylum. Compared to all other reasons combined, immigration for family reunification was associated with the lowest ALS (1.94±1.51 vs. 3.03±1.86,
P
=.03). Smoking, alcohol intake and physical activity did not differ in adulthood AI living in the US for <10y vs. ≥10y (all
P
≥.2) suggesting AI do not develop unhealthy assimilation behaviors.

Conclusions:
As measured by ALS, the physiologic dysregulation, experienced by AI is mitigated by younger age of immigration and family reunification. To decrease ALS in AI, family reunification may be more valuable than lifestyle intervention or medical therapy.
Abstract 12465: Association of Markers of Electrical Heterogeneity With Premature Ventricular Contractions on 12-Lead Electrocardiogram
Authors: Maan Abhishek , Waks Jonathan W , German David , Kabir Muammar , Thomas Jason , Sedhaghat Golriz , Sitlani Colleen , Biggs Mary , Sotoodehnia Nona , Siscovick David , Biering-Soresen Tor , Soliman Elsayed Z , Heist E. Kevin , Solomon Scott , Post Wendy , Buxton Alfred E , Josephson Mark , Tereshchenko Larisa
Published: April 2024

Introduction:
It was recently shown that independent electrophysiological substrate, quantified by global electrical heterogeneity (GEH) measures on ECG, is associated with Sudden Cardiac Death (SCD). However, mechanisms of GEH development are incompletely understood.

Hypothesis:
We hypothesized that the presence of premature ventricular contractions (PVCs) on 12-lead ECG is associated with GEH.

Methods:
We analyzed 20,288 participants from the Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Studies (CHS). Linear regression models were adjusted for demographics, structural heart disease and its risk factors to assess the association between PVCs and GEH. In a subsequent analysis, we included only those participants (n =478) who had both (a): monomorphic (if multiple) or single PVCs and (b): normal median sinus beat . The distance between PVC’s QRS vector and sinus T vector was calculated assuming the heart as a global structure. Prematurity index (PI) was defined as coupling interval (CI) divided by mean sinus-beat RR interval. SAI QRST (sum absolute interval of QRST interval) was measured as the arithmetic sum of areas under the QRST curve.

Results:
After adjusting for structural heart disease and its risk factors, the presence of PVCs was associated with a QRS-T angle widening by 6.9 (95% CI: 4.41-9.41) degrees (p < 0.0001), and SAI QRST increase by 7.03 mV*ms (95% CI: 2.58-11.48, p = 0.002). On comprehensive adjustment using our linear regression model, among those with PVCs, 1 standard deviation of decrease in the distance between PVC’s QRS-vector and sinus beat’s T-vector was associated with spatial QRS-T angle increase by 3.6 (95% CI: 0.3-7.2) degrees (p =0.048). In the same model increase in PI by 10% was associated with spatial QRS-T angle increase by 3.0 (95%CI 0.7-4.9) degrees (P=0.010).

Conclusions:
The presence of PVCs is independently associated with an increase in the GEH. Better alignment between PVC’s QRS-vector and sinus beat’s T-vector (presumed cardiac memory) and less premature PVC was independently associated with wider spatial QRS-T angle.
Abstract 12498: Antihypertensive Medication Use and Blood Pressure Control Among 384000 Chinese Adults: Pilot Results From the China PEACE Million Persons Project
Authors: Lu Yuan , Lu Jiapeng , Cheng Xiuyuan , Mu Lin , Wang Xiaochen , Li Xinyue , Linderman George , Zhang Haibo , Zhao Hongyu , Spatz Erica , Wu Chaoqun , Su Meng , Liu Jiamin , Spertus John , Masoudi Frederick , Krumholz Harlan , Jiang Lixin
Published: April 2024

Introduction:
While high blood pressure (BP) is a leading risk factor for cardiovascular diseases, little is known about the current status of treatment and BP control in China. This study aims to characterize the patterns of antihypertensive medication use and BP control in a recent Chinese national screening project.

Methods:
During the pilot phase of the China PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project, 384,234 adults aged 40-75 years were enrolled from the general population in four provinces in China between 2014-2015. We describe the prevalence, awareness, treatment, and control of hypertension in the study population, assess antihypertensive medication use, and characterize patients with uncontrolled hypertension using multivariate regression models. Hypertension was defined as BP ≥140/90mmHg, current antihypertensive medication use, or prior hypertension diagnosis. Awareness and control were defined as self-reported prior diagnosis and BP<140/90 mmHg, respectively, among those with hypertension.

Results:
The prevalence of hypertension in middle-aged Chinese adults was 43.7%; the awareness, treatment, and control of hypertension were 38.6%, 28.2%, and 8.2% (Figure). Among patients receiving antihypertensive medication, 85.5% used one medication and 13.5% used two. Calcium channel blockers (CCB) were most commonly used (56.1%), followed by angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) (19.6%); CCB plus ACEI/ARB was the most commonly used combination therapy regimen (7.6%). Men, lower income, less education, and obesity were associated with uncontrolled hypertension (all p values<0.05).

Conclusions:
Awareness, treatment, and control of hypertension were low in middle-aged Chinese adults, far lower than those in the United States. Improving BP control in China will likely require

improving diagnosis and more aggressive treatment.
Abstract 12533: Pulmonary Hypertension due to Left Atrium Stenosis Caused Intrapulmonary Venous Arterialization in Rats
Authors: Fujimoto Yoshitaka , Urashima Takashi , Akaike Toru , Kusakari Yoichiro , Minamisawa Susumu
Published: April 2024

Introduction:
Pulmonary hypertension (PH) due to left heart diseases (PH-LHD) is known as the most frequent cause of PH. Although pulmonary artery hypertension have been intensively investigated, the pathological mechanism and treatment of PH-LHD still remain unclear because of the lack of an adequate animal model of PH-LHD.

Objective:
The aim of this study was to investigate the pathophysiological characters of a novel rat model of PH-LHD caused by left atrium stenosis (LAS).

Methods:
Five-week-old male Sprague-Dawley rats were randomly divided into the two groups: the LAS and sham-operated control (SOC) groups. Through open heart surgery under anesthesia, LAS was generated by clipping the LA using HORIZON
TM
ligation clip (n=5). Thymectomy was only done in SOC group (n=5). Echocardiography was performed every 2 weeks after operation, and hemodynamic measurements and tissues were collected 10 weeks after operation.

Results:
Left ventricular (LV) inflow velocity measured by echocardiography was higher in LAS than in SOC group (2.2±0.2 and 1.1±0.03 m/s,
p
<0.01). Right ventricular (RV) pressure and RV pressure/LV pressure ratio were significantly increased in LAS than in SOC group (40.6±14.4 and 18.0±5.0 mmHg,
p
<0.01, 0.52±0.10 and 0.22±0.09,
p
<0.01, respectively). In addition, RV was weighted more in LAS than in SOC group (242±28 and 164±36 mg,
p
<0.01). Histological examination revealed that not only pulmonary arteriopathy with isolated medial hypertrophy, but also pulmonary venous arterialization in LAS group. Pulmonary venous media was significantly thickened in all of LAS rats when compared with that in SOC group. Furthermore, α-smooth muscle actin, ephrin-B2, and EphB4 (ephrin-B2 cognate receptor) were significantly increased in LAS group by immunohistological and real-time PCR analyses.

Conclusions:
We succeeded in establishing a novel, reliable rat model of PH-LHD by generating LAS for the first time in the world. Although PH was relatively mild, the PH-LHD model rats demonstrated the characteristic intrapulmonary venous arterialization and should be utilized to further investigate the mechanism of PH-LHD.
Abstract 12534: Clinical Impact of Gap Angle Ratio in Patient With Ostial Lesion of Right Coronary Artery Undergoing Percutaneous Coronary Intervention
Authors: Ohashi Koichi , Abe Daisuke , Hirano Hitoshi , Sassa Tatsuro , Takayama Akira , Kaneko Masakazu , Harunari Tomohiko , Yui Yoshiaki , Kuroki Norihiro , Yuba Takao , Suzuki Kou
Published: April 2024

Background:
However in drug-eluting stent (DES) era, ostial lesion of right coronary artery (RCA) is associated with high incidence of in-stent restenosis (ISR). And the issue of DES implantation in ostial lesion of RCA has not been adequately evaluated.

Objective:
The purpose of this study is to investigate the incidence of ISR and the predictive value in patients with ostial lesion of RCA who underwent percutaneous coronary intervention (PCI).

Methods:
A cohort of 56 patients (73.4±9.9 years-old, 70% male) who underwent PCI for ostial lesion of RCA was retrospectively analyzed in Tokyo Metropolitan Bokutoh hospital from November 2001 to October 2015. We investigated the angle between greater curvature of aortic wall and RCA take-off at diastolic and systolic phase in left anterior oblique (LAO) position view. Clinical outcome was defined as ISR at follow up coronary angiography. We performed receiver operating characteristic analysis for ISR.

Results:
Incidence of ISR was 41.1% (n=23) in entire patients. Area under the curve of Gap (angle difference between maximum and minimum) / minimum Angle Ratio (GAR-min) for ISR was 0.723 and the cut off value was 0.306 (specificity 0.818, sensitivity 0.696). We divided patients into 2 group; Low GAR group (<0.306: n=35); High GAR group (≥0.306: n=21). There were no significant differences between 2 groups in baseline characteristics. ISR was significantly lower incidence in Low GAR compared with High GAR (22.9% vs. 71.4%, p<0.001). GAR>0.306 was an independent predictor of ISR after adjustment of multiple cofounders (OR: 8.54, 95% CI: 2.18-33.1, p=0.002).

Conclusion:
These data suggest that High GAR (≥0.306) may predict ISR in patient undergoing PCI to ostial lesion of RCA.
Abstract 12559: Chronic GPER Activation Attenuates Cardiac Dysfunction in a Male Mouse Model of Progressive Heart Failure: Insights Into Cellular Mechanisms
Authors: Zhang Xiaowei , Li Tiankai , Wang Hao , Cheng Heng-Jie , Li Weimin , Ferrario Carlos M , Groban Leanne , Cheng Che Ping
Published: April 2024

Background:
Activation of G protein-coupled estrogen receptor, GPER, has been shown to exhibit beneficial actions in several cardiovascular diseases, including heart failure (HF). While reports on GPER have highlighted mostly female sex-specific health issues, recent evidence indicates its cardiovascular benefits may include the opposite sex. However, the exact means by which GPER affords cardioprotection are unclear. Moreover whether and how GPER activation may limit HF progression and have a salutary role in males is unknown. We tested the hypothesis that chronic GPER activation by its specific agonist G
1
improves myocyte function and [Ca
2+
]
i
regulation, thus limiting HF progression in male mice.

Methods:
We simultaneously examined LV and myocyte function and [Ca
2+
]
i
transient ([Ca
2+
]
iT
) responses in 3 groups of male mice (11/group) over 4 weeks (W):

HF

receiving the initial injection of isoproterenol (ISO) (150 mg/kg sq for 2 days) over 2 W, then receiving placebo;

HF/G
1

after ISO for 2W, then receiving G
1
(150 μg /kg/day sq via mini pump), given for 2W; and

controls

.

Results:
Compared with controls, both Echo and hemodynamic assessments revealed that ISO-treated mice had HFpEF onset at 2 W after ISO and progressed to mild HF at 4 W with LV dilatation, increased LV time constant of relaxation (τ) (5.4 vs 3.1 ms), and 52% reductions in peak rate of mitral flow (dV/dt
max
); accompanied by significantly reduced myocyte contraction (dL/dt
max
, 102.7 vs 143.6 μm/s), relaxation (dR/dt
max
,69.9 vs 107.9 μm/s) and [Ca
2+
]
iT
(0.16 vs 0.21). Importantly, compared with normal myocytes, ISO (10
-8
M) caused significantly less increases in dL/dt
max
(24% vs 61%), dR/dt
max
(23% vs 57%), and [Ca
2+
]
iT
(15% vs 30%) in HF myocytes. HF/G1 rats, compared to HF, showed significantly increased LV dV/dt
max
and decreased t (4.0 ms) accompanied by increased dL/dt
max
(142.6 μm/s), dR/dt
max
(107.9 μm/s) and [Ca
2+
]
iT
(0.21). Moreover, ISO-induced increases in dL/dt
max
(61%), dR/dt
max
(56%), and [Ca
2+
]
iT
(30%) in myocytes from HF/G
1
were significantly augmented, similar to controls.

Conclusions:
Chronic G
1
treatment restores normal myocyte basal and β-AR stimulated contraction, relaxation and [Ca
2+
]
i
regulation, leading to regression of LV dysfunction in a male mouse model of HF.
Abstract 12593: Improvement in Aortic Vascular Inflammation by 18-FDG PET/CT Associates With Reduction in Aortic Wall Thickness by MRI
Authors: Kabbany Mohammad T , Dey Amit K , Shukla Parag , Chaturvedi Abhishek , Lerman Joseph B , Aberra Tsion M , Joshi Aditya A , Silverman Joanna I , Ng Qimin , Teague Heather L , Dahiya Asha , Rodante Justin A , Ahlman Mark A , Playford Martin P , Mehta Nehal N
Published: April 2024

Introduction:
The presence of aortic vascular inflammation (VI) by 18-FDG PET/CT predicts future cardiovascular (CV) events. Furthermore, aortic wall thickness by MRI has been shown to be an important marker of early subclinical atherosclerosis. Whether improvement in aortic vascular inflammation by FDG PET/CT is associated with improvement in aortic wall thickness by MRI is not known.

Hypothesis:
We hypothesized that an improvement in VI by FDG PET/CT will associate with an improvement in aortic wall thickness by MRI in a well characterized cohort of Psoriasis (PSO) patients.

Methods:
Consecutively recruited PSO patients (N=64) underwent whole-body PET/CT and MRI exams at baseline and 1-year follow-up. VI was assessed as target-to-background ratio (TBR) [Excellence Brilliant Workstation]. To measure aortic wall thickness, wall boundaries of the thoracic descending aorta were traced on each MRI slice [Qplaque, Medis]. The longitudinal change in wall thickness of the thoracic descending aorta was analyzed using unadjusted and adjusted multivariable regression (STATA 12).

Results:
The cohort was middle-aged (mean±SEM 50.67±1.80) and had a low cardiovascular risk by Framingham risk score [median-3, IQR- (1-7)]. Overall the cohort had an average TBR of 1.74±0.02 consistent with moderate vascular inflammation. At follow-up, the total cohort had a mean improvement in TBR of 7.47% (p<0.001) with use of topical therapy (64%), biological therapy (59%) and UVB (13%). Improvement in TBR of the aorta was associated with reduction in mean wall thickness of the descending thoracic aorta beyond adjustment for traditional risk factors, statin use, & systemic/biologic PSO therapy (β=0.30, p = 0.03).

Conclusions:
Improvement in aortic VI by FDG PET/CT was associated with reduction in aortic wall thickness by MRI at one year, suggesting a reduction in VI may improve early atherosclerosis. Our findings suggest that an improvement in vascular inflammation may mitigate structural abnormalities of the aorta. Randomized controlled studies are needed to confirm these findings.
Abstract 12633: Echocardiographic Evaluation of Cardiac Function and Hemodynamic During LVAD-based Resuscitation in Pigs
Authors: Zayat Rashad , Hatam Nima , Ebeling Andreas , Nix Christoph , Marx Gernot , Autschbach Rüdiger , Fries Michael , Derwall Matthias
Published: April 2024

Introduction:
We have previously shown that primary survival after cardiac arrest (CA) can be improved by optimizing circulation during CPR using a minimal invasive left ventricular assist device (Impella 2.5, iCPR). Whether calculated flow values derived from the Impella Controller during CA are reliable is unknown.

Hypothesis:
iCPR provides a preservation of right (RV) and left ventricular (LV) function following CA. The transpulmonary flow (TPF) inferred by pulsed-wave Doppler (PWD) during iCPR correlates well with the calculated blood-flow derived from the LVAD controller

Methods:
Ventricular fibrillation (VF) was electrically induced in 5 anesthetized pigs. Animals were left untreated for 10 minutes before iCPR was attempted. In addition to invasive hemodynamic monitoring, all animals received transesophageal echocardiography at baseline, during untreated cardiac arrest, at the initiation of iCPR, 30 minutes, and 5 hours following ROSC.

Results:
Preservation of systolic biventricular function within the first 5 hours following ROSC was observed in all individuals. All functional parameters almost returned to baseline values: baseline vs. 5hrs after ROSC: global longitudinal strain (GLS): -25±4.3% vs. -20±2.7%;
p
=0.388; ejection fraction: 64±8.8% vs. 61.32±10.3%,
p
=0.971;Stroke volume index: 28.32±8.9 vs. 24.71±12.86 mL/m
2
,
p
=0.545. The unloading of the LV volume was sufficient (LV-end-diastolic volume (mL): baseline, cardiac arrest, 30min after iCPR, 5hrs. after ROSC: 55.38±2.8, 64.7±9.9, 45.69±7.4, 49.46±13.9). PWD derived TPF during VF correlated well with the calculated flow (TPF: 1.8±0.39 L/min, Impella-Flow: 1.7±0.28 L/min.,
r
=0.868, CI: -0.05842 to 0.9912,
p
=0.056). RV systolic function did not recover within the same time frame as compared to LV: baseline vs. 5 hrs after ROSC: Tricuspid annular systolic velocity: 11.6±1 vs. 8.5±1 cm/s,
p
=0.005, RV-fractional area shortening: 42±6.2 vs. 33±6.9 %,
p
=0.006.

Conclusion:
iCPR during cardiac arrest provided sufficient unloading of the LV as well as protection and preservation of the LV systolic function. The calculated Impella flow during iCPR correlated well with PWD derived TPF. Further studies are required to quantify effects of iCPR on changes in RV function.
Abstract 12756: 11 year Trends and Utilization Patterns of Cardiac Implantable Electronic Devices in Patients Diagnosed With Sick Sinus Syndrome
Authors: Guha Avirup , Xiang Xiao , Patel Dilesh , Fedorov Vadim V , Daoud Emile G
Published: April 2024

Background:
CIEDs (cardiac implantable electronic devices) are commonly used for managing sick sinus syndrome (SSS).

Hypothesis:
Compare features of SSS patients (pts) who did and did not receive CIED.

Methods:
Pts were identified from the National Inpatient Sample dataset (2003-13). Included pts were ≥18, had a primary diagnosis of sinus node dysfunction and atrial arrhythmia (hence SSS). Pts who died, transferred out or had prior CIED were excluded. Included pts were then stratified by implantation of a CIED. Data regarding SSS and weighted multivariable model of factors associated with CIED implantation are presented.

Results:
Over 11 years, 421,535 pts were diagnosed with SSS (mean annual incidence of 38,321 ± 4,258) and the trend for SSS hospitalization fell 19% (p < 0.001). CIED were implanted in 353,247 pts (83.8%) and the annual trend of CIED use was decreasing (p < 0.001). Of 39 variables analyzed, the attached forest plot shows only those variables that were either associated with a lower likelihood (down arrow) or with a higher likelihood (up arrow) for CIED implantation. Lower likelihood for CIED was associated with young age, female, African American race, self-pay, heart failure, COPD, kidney disease, emergency room admission, weekend admission, public/rural/urban nonteaching/small/medium hospitals, midwest/south/west regions and reduced inpatient and procedural volume. Greater likelihood for CIED implant was associated older age, Hispanic race, HTN, hyperlipidemia, coronary artery disease, and increased procedure volume.

Conclusions:
Analyzing a large US database over 11 years demonstrates falling hospitalizations and CIED implantation for SSS. There are a number of relevant variables that impact if a CIED is utilized that include not only clinical features but also nonclinical variables such as socioeconomic status, gender, type and location of hospital and hospital procedure volume.
Abstract 12761: The Association of Resting and Exercise Ventricular-Vascular Coupling With Heart Failure Hospitalization in Patients With Stable Coronary Heart Disease and Preserved Systolic Function: The Heart and Soul Study
Authors: Fitzpatrick Jesse K , Schiller Nelson B , Whooley Mary A , Mishra Rakesh K
Published: April 2024

Introduction:
The ventricular-vascular coupling ratio (

E
A
/E
ES

) is defined as the ratio of arterial

(E
A
)

to left ventricular elastance

(E
ES
)

and is a key determinant of cardiac performance. Contractile reserve with exercise is inversely related to changes in the

E
A
/E
ES

in healthy patients. However, the prognostic value of the

E
A
/E
ES

at rest and its change with exercise has not been evaluated in patients with stable coronary heart disease (CHD) and preserved systolic function.

Methods:
Among 647 patients with stable CHD and left ventricular ejection fraction ≥50%, we evaluated the association of baseline echocardiographically-determined

E
A

,

E
ES

, and

E
A
/E
ES

,
at rest and at peak exercise, with subsequent heart failure hospitalization (HF) during 7.5±2.8 years of follow-up.

Results:
Both

E
A

(2.1±0.7 to 3.0±1.6 mmHg/mL, p<0.001) and

E
ES

(4.0±1.63 to 7.0±4.5 mmHg/mL, p<0.001) increased significantly with exercise compared to rest.

E
A
/ E
ES

decreased from 0.67±0.40 at rest to 0.63±0.52 at peak exercise (p=0.001). Overall, 75 (12%) patients were hospitalized for HF. In multivariable adjusted models, participants with higher resting

E
ES

(HR 0.75 per mmHg/mL increase, 95% CI 0.61 - 0.89, p = 0.004) were at lower risk for HF hospitalization while those with higher resting

E
A
/E
ES

(HR 5.0 per unit increase, 95% CI 1.19 - 12.85, p<0.001) were at increased risk for HF hospitalization. With exercise, each doubling of

E
A
/E
ES

was associated with a 25% increased risk of incident HF in the fully adjusted model (H.R. 1.25 per doubling, 95% C.I. 1.08-1.45, p<0.002). Neither resting

E
A

nor its change with exercise predicted HF hospitalization.

Conclusions:
In patients with stable CHD and preserved systolic function,

E
A
/E
ES

decreases with exercise while both its components, arterial and ventricular elastance, increase. A higher resting

E
A
/E
ES

and its increase with exercise are independently associated with an increased risk of HF hospitalization.
Abstract 12767: Trajectory of Exercise Capacity in Childhood and Its Impact on Their Adult Pathophysiology in Patients After the Fontan Operation
Authors: Ohuchi Hideo , Negishi Jun , Hayama Yosuke , Noritake Kanae , Miyazaki Aya , Shiraishi Isao
Published: April 2024

Background:
Preserved exercise capacity in childhood may predict better long-term outcome in patients after the Fontan operation.

Purpose:
This study was to elucidate an impact of trajectory of exercise capacity in childhood on the long-term exercise capacity and non-cardiac multi-organ function.

Method and Results:
Since 1990, consecutive 197 Fontan patients had undergone two serial cardiopulmonary exercise testing (CPX) at the age of 8±2 and 14±2 years and we measured the change in %-predicted peak oxygen uptake (dPVO
2
: %). Of these, 94 patients had performed CPX in the adulthood (24±4 years). Our patients were subdivided into 2 groups; those with positive dPVO
2
(n=113, group I) and those with negative dPVO
2
(n=84, group D). Early era at operation, heterotaxy, protein losing enteropathy, high PVO
2
and plasma brain natriuretic peptide levels (BNP) at 1
st
CPX had independent negative impact on dPVO
2
(p<0.05-0.0001). Group I showed significantly higher PVO
2
and lower BNP in their adulthood, while 49 clinical events, including 9 deaths occurred after 2
nd
CPX. When compared with group I, group D had high hazard ratio of 2.1 and 6.5 for morbidity and mortality, respectively (p<0.05 for both); however, there were no differences in high prevalence of impaired glucose tolerance, liver MELD XI score, or 24-hour creatinine clearance between two groups in their adulthood.

Conclusions:
The trajectory of exercise capacity in childhood is improving in current Fontan children which is associated with better prognosis, higher PVO
2
and lower BNP in the adulthood. However, the non-cardiac multi-organ dysfunction may progress regardless of the trajectory.
Abstract 12810: Defining the Role of Mitral Regurgitation on Left Atrial Function During Exercise in Left Heart Disease: Insights From CPET Combined With Exercise Echocardiography
Authors: Sugimoto Tadafumi , Bandera Francesco , Generati Greta , Alfonzetti Eleonora , Tufaro Vincenzo , Guazzi Marco
Published: April 2024

Background:
The role of mitral regurgitation (MR) on left atrial dynamics has not been characterized especially during exercise. Its definition might provide additional clues on the pathogenesis of exercise intolerance in patients with cardiac disorders. We aimed at this goal.

Methods:
73 heart failure with reduced (n=51) and preserved (n=21) ejection fraction, 53 aortic stenosis, 27 primary mitral regurgitation, 14 hypertrophic cardiomyopathy, and 42 control subjects underwent cardiopulmonary exercise testing evaluation combined with Echo-Doppler with assessment of left atrial strain (LAS) and MR entity. Patients were divided according to the severity of MR and no MR.

Results:
LAS during exercise compared to rest was significantly increased in no MR (n=92, 27 ± 10 vs 33 ± 13%, P <0.001) and mild MR (n=41, 24 ± 11 vs 26 ± 15%, P <0.05) group but not in mild-moderate MR (n=31, 20 ± 9 vs 23 ± 14%, P=0.05), moderate-severe MR (n=23, 18 ± 12 vs 19 ± 16%, P=0.4), and severe MR (n=19, 17 ± 14 vs 19 ± 14%, P=0.01) group by visual assessment of the severity of MR during exercise (figure). In 54 patients with MR assessed using proximal isovelocity surface area method both at rest and exercise, effective regurgitant orifice (ERO: 19 ± 12 vs 26 ± 16 mm
2
, P <0.001) and regurgitant volume (31 ± 19 vs 40 ± 24 mL, P <0.001) were significantly increased during exercise, and there was no change in LAS during exercise (17 ± 11 vs 18 ± 14%, P=0.4). A progressive impairment in exercise ventilation efficiency assessed by minute ventilation-carbon dioxide production (VE/VCO2 slope) was observed according to ERO entity (ERO: <20 mm
2
, VE/VCO2 slope: 30 ± 7; ERO: 20-40 mm
2
, VE/VcO2 slope: 33 ± 6; ERO: >40 mm
2
, VE/VCO2 slope: 39 ± 17, P <0.05).

Conclusions:
In left heart disease patients of any origin, an impaired LAS response during exercise is associated with the presence of MR during exercise. This unfavorable pathophysiological and functional response leads to an impaired exercise tolerance and ventilatory inefficiency.
Abstract 12831: Coupling Factor 6 Accelerates Aging by Synchronizing Primary Aging Hallmarks Such as Telomere Attrition and a Blocking Effect of Atpase Inhibitory Factor 1
Authors: Osanai Tomohiro , Tanaka Makoto , Tomita Hirofumi , Kobayashi Akihiro , Okumura Ken
Published: April 2024

Introduction:
A transient low pH stressor gives great impacts to the nucleus, but little is known about the effect of chronic pH stressor on aging and lifespan. We identified that coupling factor 6 (CF6) induces long-term low pH in the cells by enhanced proton import through ecto-F
1
F
o
complex and by reduced proton export through inhibition of Na
+
-K
+
ATPase. We analyzed whether and how CF6-induced acidosis affects aging and lifespan, being focused on primary aging hallmarks of genomic instability, telomere attrition, epigenetic alterations, and defective proteostasis.

Methods and Results:
CF6 overexpressing transgenic mice (TG, n=20) manifested early senescence-associated phenotypes such as signs of hair graying and sparseness, resulting in shortened lifespan compared with wild-type mice (WT, n=13) (median values; 108±2 vs 131±11 weeks, p<0.05). Long-term low pH disturbed nuclear envelope protein emerin as genomic instability and elevated aging-associated markers of global hypo-methylated DNA, histone 3 lysine 4 (H3K4) and H4K20 trimethylation, and H4K5 acetylation by decreased nucleoplasmic HDAC3, a binding partner of emerin. Leukocyte telomere length was shorter in TG compared with WT at the age of 100 weeks. Microarray analysis showed that a target molecule of three primary hallmarks was autophagy-related Atg7 that is commonly decreased in TG tissues. Chronic acidosis decreased and acetylated Atg7 protein in the TG heart and kidney without affecting insulin signaling. In TG cells, LC3 II and lysosome were located more weakly and diffusely in the cytoplasm compared with strong peri-nuclear staining in WT, being dependent on acetylation of LC3 II that inhibits cytoplasmic translocation. ATPase inhibitory factor 1 (IF1), an endogenous inhibitor for CF6, repaired subcellular localization of LC3 II and lamp1, and restored the decrease in Atg7 and emerin and the increase in H4K5ac. ChIP assay revealed that PCR in the repressor-binding region of Atg7 promoter at -441 through -763 was increased by CF6 after immuneprecipitated with anti-acetyl H4K5, anti-trimethyl H3K4, and H4K20 antibodies.

Conclusions:
Long-term low pH switches on aging by onset and synchronization of primary aging hallmarks, and provides a novel target for anti-aging therapy.
Abstract 12845: Renal Biomarkers Predict Long-Term Adverse Events in Patients With Type 2 Diabetes Mellitus and Recent Acute Coronary Syndrome: Insights From the EXAMINE Trial
Authors: Vaduganathan Muthiah , White William B , Charytan David M , Morrow David A , Liu Yuyin , Wilson Craig , Kupfer Stuart , Zannad Faiez , Cannon Christopher P , Bakris George L
Published: April 2024

Introduction:
Prediction of cardiovascular (CV) risk in patients with type 2 diabetes mellitus (T2DM) remains incomplete. Measurement of renal biomarkers may facilitate early risk stratification in high-risk patients with T2DM.

Methods:
We evaluated the prognostic performance of 4 urinary and 1 serum renal biomarkers for major cardiovascular events in 5,380 patients with T2DM and recent acute coronary syndrome (ACS, within 15-90d) enrolled in the EXAMINE trial. Patients requiring dialysis within 14d of screening were excluded. Cystatin C, markers of kidney injury, including neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule (KIM)-1 protein, and indices of urinary protein excretion were measured at randomization (a median of 45 days after ACS). CV events at 24-mo were estimated by the Kaplan-Meier method. Single- and multi-biomarker covariate-adjusted Cox proportional hazards models were created to predict times to events.

Results:
In EXAMINE, median age was 61y, 68% were male, and median baseline estimated glomerular filtration rate (eGFR) was 71.2 ml/min/1.73 m
2
. During follow-up, 326 (6.1%) patients had died. All renal biomarkers were robustly associated with long-term adverse CV events in graded fashion (P≤0.006 for all trends;
Table
). Risk prediction for all 5 renal biomarkers was independent of major covariates including baseline eGFR for all major clinical endpoints (
Table
). However, when simultaneously accounting for all biomarkers, only Cystatin C (standardized) was predictive of all-cause mortality (HR 1.51 [1.30, 1.74]; p≤0.001), heart failure hospitalization (HR 1.20 [0.96, 1.49]; p=0.107), and major CV events (HR 1.28 [1.14, 1.45]; p≤0.001).

Conclusions:
These data from the EXAMINE trial represent one of the largest experiences to support the prognostic value of multiple novel and traditional renal biomarkers in predicting long-term adverse CV events in high-risk patients with T2DM, beyond baseline eGFR.
Abstract 12895: Characteristics and Outcome of Ventricular Tachycardia in Advanced Fabry Disease Cardiomyopathy
Authors: Oder Daniel , Liu Dan , Hu Kai , Salinger Tim , Weidemann Frank , Ertl Georg , Wanner Christoph , Nordbeck Peter
Published: April 2024

Introduction:
Ventricular tachycardia (VT) are suspected the leading cause of premature death in patients with advanced Fabry cardiomyopathy. However, origin and outcome of respective tachyarrhythmic events have yet not been comprehensively investigated.

Methods:
All patients (n=261) in care at the Fabry Center for Interdisciplinary Therapy (FAZIT) Würzburg, Germany, with history of (n=17) or demand for (n=1) implantable cardioverter defibrillator (ICD) device therapy for primary or secondary prevention of ventricular tachyarrhythmic events due to advanced Fabry cardiomyopathy underwent comprehensive clinical investigations including analysis of 12-lead ECG, 24-hour Holter ECG, and ICD Holter chart reviews for documented VT episodes with special focus on characteristics and outcome of respective events.

Results:
Study subjects were mainly of male gender (14/18, 78%) and middle aged (55±10 years, range 33-74) at point of ICD demand. In total, 11/18 patients (61%) suffered from at least one episode of VT. All documented episodes were sustained monomorphic ventricular tachycardia. Most 12-lead ECG documented VT events (n=7) were self-terminated (n=6, 86%). Five subjects were in need of anti-tachycardia overdrive pacing and four of shocks for termination of respective VT events when followed over time. Analyzing VT episodes documented in 12-lead ECG showed a correlation of VT episode origination from the area of myocardial replacement fibrosis, mostly from the postero-lateral wall segments of the left ventricle. Radiofrequency catheter ablation was performed in three patients (17%), of whom two still suffered from VT episodes afterwards and both finally died due to end-stage heart failure complications. Three other subjects from this group also died due to cardiac events (in total 4/18, 22%), whereas one (6%) due to Fabry-associated stroke.

Conclusions:
VT is common in advanced Fabry disease. As all documented VT episodes were monomorphic, radiofrequency catheter ablation might represent a yet underestimated therapy option besides ICD device therapy. However, due to end-stage heart failure associated complications, cardiac mortality remains a substantial factor questioning the clinical impact and benefit in end-stage Fabry disease.