bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15022: Alkaline Phosphatase Activity After Infant Cardiac Surgery: Kinetics and Association With Post-operative Cardiovascular Support
Authors: Davidson Jesse , Urban Tracy T , Tong Suhong , Twite Mark , Baird Christine , Khailova Ludmila , Jaggers James , Wischmeyer Paul
Published: April 2024

Introduction:
Alkaline phosphatase (AP) may be protective after CV surgery through dephosphorylation of endotoxin and extracellular adenine nucleotides. AP activity falls after infant CV surgery and low activity is associated with increased support requirements. However, the kinetics of AP loss and recovery, the isoenzymes involved, and the temporal relation of low AP activity to increased support are unknown. We hypothesized loss of all isoenzymes during surgery leads to decreased AP activity and that early low AP activity is associated with increased cardiovascular support at 6-48hr.

Methods:
Prospective study of 93 infants <120 d/o undergoing CV surgery with bypass. Total/isoenzyme specific AP activity and vasoactive inotropic score (VIS) were obtained pre-operation, pre-separation and at 6, 24, 48 and 72hr after ICU admission. AP activities were determined by commercial assay and concentration by multiplex immunoassay. Low AP activity was defined as ≤80 U/L.

Results:
Median AP activity decreased through 6hr due to decreased bone and liver 2 isoenzyme activities (fig 1). Liver 1 isoenzyme increased post-bypass then decreased through 72hr. Activity was highly correlated with concentration at all time points (r=0.83-0.89; p<0.0001). Nadir AP activity coincided with peak VIS. Infants with low AP activity at 6hr had significantly higher VIS through 48hr (6hr 12.1 vs 8.1, p<0.0005; 24hr 11.2 vs 5.3, p<0.0001; 48hr 6.9 vs 3.0, p<0.0005). Similar findings occurred with low pre-separation and 24hr AP activity. On multivariate analysis, low AP activity at 6hr was independently associated with higher VIS at 6, 24 and 48hr.

Conclusions:
Loss of bone and liver 2 isoenzymes leads to decreased AP activity after infant CV surgery. Low early AP activity is associated with increased cardiovascular support requirements 6-48hr later. AP activity may serve as an early biomarker of post-operative hemodynamic instability and a potential therapeutic target in this population.
Abstract 15042: The First Clinical Use of Fractional Flow Reserve Derived From Coronary CT Angiography (FFR-CT) in the ‘Real World’ Predicts Standard of Care Guided Revascularization
Authors: Packard Rene R , Nakanishi Rine , Lajoie Alexandra , Buddoff Matthew J , Karlsberg Ronald P
Published: April 2024

Introduction:
Fractional flow reserve computed tomography (FFR-CT), approved by the FDA in November 2014, provides functional assessment of anatomic severity and blood flow in the coronary arteries without changes in acquisition, medication, contrast or radiation, with an area under the receiver-operating characteristic curve of 0.90 compared to invasive FFR. We obtained FFR-CT in the largest group of patients in the United States post-FDA release and applied this measure to patients who had previously undergone invasive coronary angiography after baseline Coronary CTA.

Hypothesis:
To determine whether FFR-CT predicts subsequent coronary revascularization in patients who underwent Coronary CTA prior to invasive angiography and were treated with standard of care in a large urban Cardiology practice.

Methods:
Consecutive patients who underwent Coronary CTA followed by invasive angiography over a 12-month period from 2012-2013 were identified. Studies that did not fit inclusion criteria (e.g. prior revascularization, motion artifact, severe calcification) were excluded. The remaining studies (n=61) were sent for FFR-CT analysis and patients who received stents (n=15) were identified. FFR-CT values were compared in territories that were stented (n=15) with those that were not (n=163). Baseline FFR-CT values were obtained retrospectively, and therefore results did not interfere with clinical decision-making.

Results:
In territories that were not intervened upon, baseline FFR-CT values had a median of 0.87, with 75% of territories displaying an FFR-CT > 0.80. In territories that underwent PCI, baseline FFR-CT values were all < 0.75, with a median of 0.65 (P<0.0001 PCI vs. no stent). Of 18 patients with an FFR-CT < 0.70; 11 underwent PCI, 2 had chronic total occlusions and the remaining 5 pursued aggressive medical management based on clinical judgment.

Conclusions:
We established baseline FFR-CT values in patients who underwent PCI in the real world outside of a research protocol. The role of FFR-CT in clinical decision-making and to determine the need for revascularization requires prospective trials; however FFR-CT determined prior to invasive coronary angiography accurately predicts subsequent revascularization in clinical practice.
Abstract 15062: Incremental Prognostic Utility of LV Global Longitudinal Strain and Functional Capacity in Asymptomatic Patients With Significant Primary Mitral Regurgitation and Preserved Left Ventricular Ejection Fraction Undergoing Rest-Stress Echocardiography
Authors: Mentias Amgad , Naji Peyman , Barr Tyler , Gillinov A. Marc , Rodriguez L. Leonardo , Mihaljevic Tomislav , Sabik Joseph F , Griffin Brian P , Desai Milind Y
Published: April 2024

Background:
Outcomes after mitral valve (MV) surgery for primary mitral regurgitation (PMR) are excellent; however surgical timing in asymptomatic PMR & preserved left ventricular ejection fraction (LVEF) remains challenging. We assessed the incremental utility of resting LV-global longitudinal strain (LV-GLS) & exercise variables in asymptomatic patients with ≥3+ PMR & preserved LVEF (≥60%) who underwent rest-stress echocardiography.

Methods:
We included 737 such patients (58±13 years, 68% men) between 2000-11. Clinical, resting (including LV-GLS using Velocity Vector Imaging & right ventricular systolic pressure or RVSP) & exercise stress echo (metabolic equivalents or METs) data were recorded. Society of Thoracic Surgeons (STS) score was calculated. Primary events were death & heart failure admission.

Results:
Hypertension, atrial fibrillation (AF) and coronary artery disease were seen in 48%, 13% & 10% patients. Posterior, anterior & bileaflet prolapse were noted in 46%, 9% & 45% (20% had flail). Mean STS score, resting LVEF, resting RVSP, exercise MET’s & % age-gender predicted MET’s were 1.5±1, 62±2%, 31±12 mmHg, 9.8±3 & 115±27 respectively. 65% underwent MV surgery with mean time to surgery 13±22 months. At 6.2±3 years, events occurred in 61 (8%) patients (death in 33 patients). On multivariable Cox survival analysis, higher rest RVSP (Hazard ratio or HR 1.04), lower % age-gender predicted METS (HR 1.11), lower LV-GLS (HR 1.42), higher STS score (HR 1.12) & AF (HR 2.23) were significantly associated with events (all p<0.05). Association of MV surgery (time-dependent covariate) with outcomes was not significant (HR 0.63 [0.38-1.07, p=0.1). Figure 1a shows an incremental model with association to outcomes & 1b shows survival curves, based on LV-GLS better/worse than median (-21.7%).

Conclusions:
In asymptomatic patients with ≥3+ PMR & preserved LVEF, lower baseline LV-GLS & %age-gender predicted METs are associated with long-term adverse events.
Abstract 15108: Outcomes in Patients With Pericardial Effusion Requiring Drainage After Electrophysiology Procedures
Authors: Mentias Amgad , Horr Samuel , El-Telbany Ahmed , Kanj Mohamed , Klein Allan
Published: April 2024

Background:
Pericardial effusion (PE) is a known complication of electrophysiological procedures (EPP). We sought to describe patient characteristics and outcomes in PE requiring drainage after EPP.

Methods:
We identified 114 patients who underwent EPP at our center from 2000 to 2012 and had an intervention for new pericardial effusion up to 1 month after the EPP. Baseline demographic and clinical data were recorded. Primary outcome was 30 days mortality after PE drainage. Secondary outcome was major bleeding (drop in hemoglobin ≥ 3 gm/dl or requiring blood transfusion) after PE drainage.

Results:
Mean age was 65±13 years (48% men). Mean ejection fraction (EF) was 53±12. Hypertension and diabetes mellitus were found in 54 and 49%. Heart failure (HF) and coronary artery disease were present in 26 and 27%. Dual antiplatelet therapy was used in 6.7%, while combined Aspirin, Clopidogrel and oral anticoagulant was used in 1.7%. Intra-procedural heparin was used in 62%. Presenting symptoms were chest pain, shortness of breath and altered mental status in 51, 42 and 26%. Pulmonary vein isolation was done in 50% while pacemaker insertion and ventricular tachycardia ablation were done in 8.8 and 9.7%. Drainage of PE was done by emergent and elective pericardiocentesis in 65 and 28% while elective pericardial window and emergent sternotomy for exploration was done in 2.6 and 4.4%. Re-accumulation occurred in 12.3% and a second intervention was required in 57% of those patients. The primary outcome occurred in 2.6% and secondary outcome occurred in 45.6%. Predictors of mortality were older age, higher drop in hemoglobin, and lower EF (all p<0.05). Predictors of secondary outcome were HF and higher INR at time of procedure (both p=<0.05).

Conclusion:
Pericardial effusion after an electrophysiology procedures requiring intervention is associated with a mortality of 2.6% within 30 days. Older age, lower ejection fraction and higher drop in hemoglobin were associated with worse outcomes.
Abstract 15131: Early Withdrawal of Life-Sustaining Therapy for Perceived Neurological Prognosis is Associated With Excess Mortality After Out-of-Hospital Cardiac Arrest
Authors: Elmer Jonathan , Torres Cesar , Aufderheide Tom P , Austin Michael A , Callaway Clifton W , Golan Eyal , Herren Heather , Jasti Jamie , Kudenchuk Peter J , Scales Damon C , Stub Dion , Richardson Derek K , Zive Dana M ,   Resuscitation Outcomes Consortium
Published: April 2024

Introduction:
Withdrawal of life-sustaining therapy because of perceived poor neurological prognosis (WLST-N) is a common cause of death after out-of-hospital cardiac arrest. Guidelines recommend against WLST-N before 72 h (WLST-N<72), but WLST-N<72 remains common and may increase mortality.

Methods:
We performed a secondary analysis of the Resuscitation Outcomes Consortium’s PRIMED trial including adults surviving >1h after hospital arrival. Our main exposure was WLST-N<72, which was collected for the original trial by chart review. Outcomes were survival to hospital discharge and functionally favorable survival (modified Rankin Score ≤ 3). We used two methods to determine predicted outcomes in the cohort exposed to WLST-N<72 if WLST-N were delayed until after 72h. First, we used pre-exposure covariates to create a propensity score modeling the probability of exposure to WLST-N<72 and propensity-matched exposed to unexposed subjects, treating subjects with WLST-N after 72h as unexposed. We then determined the probability of survival and functionally favorable survival in the unexposed matched cohort. Second, we fit adjusted logistic regression models using data from the unexposed cohort and used these models to predict outcomes in the exposed cohort.

Results:
Of 16,875 OHCA subjects, 4,265 (25%) met inclusion criteria. Of these, 1,490 (35%) survived to discharge and 1101 (26%) had a functionally favorable survival. WLST-N occurred in 1626 (59% of non-survivors), most commonly on hospital day 1, and 919 (33% of non-survivors) were exposed to WLST-N<72. After matching, there were no differences between the exposed and unexposed groups. In adjusted analyses, exposed subjects had an estimated 25-26% chance of survival and 16% functionally favorable survival had they not received WLST-N<72.

Conclusion:
In this large North American cohort, death associated with WLST-N<72 was common. Extrapolating to national epidemiological data, our findings indicate that approximately 4,500 Americans annually who would otherwise survive to discharge instead die because of WLST-N<72, nearly 2,900 (64%) of whom might have had functional recovery. Reducing WLST-N<72 may be an important means to decrease mortality after OHCA and improve public health.
Abstract 15140: VEGFR2 Blockade in Murine Vein Grafts Reduces Intraplaque Hemorrhage due to Enhanced Plaque Neovessel Maturation
Authors: de Vries Margreet R , Peters Erna A , Hamming Jaap F , Goumans MarieJosé T , Quax Paul H
Published: April 2024

Introduction:
Vein graft patency rates are poor due to the development of extensive neointimal thickening, atherosclerosis and lesion instability. We have previously shown that murine vein graft lesions exhibit leaky neovessels and that intraplaque hemorrhage induces lesion growth. Immature plaque neovessels contribute to atherosclerotic plaque instability by leakage of erythrocytes and leukocytes (intraplaque haemorrhage) in the plaque. Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), together with the angiopoietin (Ang)-Tie2 system, regulates the maturation of neovessels.

Hypothesis:
VEGFR2 blockade induces plaque neovessel maturation resulting in reduced intraplaque hemorrhage and plaque instability.

Methods:
Donor caval veins were engrafted in carotid arteries of recipient hypercholesterolemic ApoE3*Leiden mice (n=14/group). Mice were treated at day 14, 17, 21 and 25 with VEGFR2 blocking antibodies (DC101) or control IgG antibodies. At day 28 vein grafts were harvested for histological and RNA analysis.

Results:
Morphometric analysis revealed a striking 50% decrease in vein graft segments that expressed intraplaque hemorrhage in the DC101 treated group. This was accompanied by a significant 25-fold decrease in extravasated erythrocytes. DC101 treatment resulted in a decrease in VEGF expression whereas VEGFR1 and VEGFR2 expression was comparable between the two groups. Connexin 37 and 43 expression was also comparable between the groups, indicating that gap junctions were not affected upon DC101 treatment. However, lesions that exhibit intraplaque hemorrhage showed a strong increase in destabilizing Ang-2. The vein graft lesion area was significantly reduced in the DC101 group, which was accompanied by an increased plaque stability phenotype as a result of a significant reduction in macrophage content and increases in smooth muscle cells and collagen content.

Conclusions:
Blockade of VEGFR2 leads to reduced intraplaque hemorrhage, decreased vein graft lesion area and increased plaque stability as a result of increased neovessel maturation. This identifies plaque neovascularization as an attractive target for the treatment of unstable atherosclerotic diseases.
Abstract 15144: LCZ696 Improves Lipid Mobilization From Adipose Tissue: A Randomized, Double-blind, Active-controlled, Parallel-group Study in Obese Hypertensive Patients
Authors: Jordan Jens , Stinkes Rudi , Jax Thomas , Engeli Stefan , Haufe Sven , Blaak Ellen , May Macus , Havekes Bas , Schindler Christoph , Albrecht Diego , Pal Parasar , Schaper Nicolaaes , van der Kolk Birgitta , Tegtbur Uwe , Heise Tim , Goossens Gijs , Langenickel Thomas
Published: April 2024

LCZ696 simultaneously inhibits neprilysin, thereby augmenting natriuretic peptide (NP) availability, and blocks AT
1
-receptors. NPs released during exercise promote lipid mobilization and oxidation. Therefore, we investigated whether LCZ696 treatment augments lipid mobilization and oxidation at rest and during exercise. In this double-blind study, 98 patients with mild-to-moderate hypertension and abdominal adiposity were randomized to LCZ696 400 mg or amlodipine (AML) 10 mg once daily for 8 weeks. At baseline and week 8, abdominal subcutaneous adipose tissue lipolysis (microdialysis), whole-body lipolysis (glycerol tracer kinetics), and substrate oxidation and energy expenditure (indirect calorimetry) were assessed at rest and during exercise (60 min cycling at approximately 50% of peakVO
2
). LCZ696 and AML groups had comparable baseline characteristics with regards to age, blood pressure and body mass index (LCZ696 32.6±4.6 kg/m
2
, AML 33.3±4.4 kg/m
2
). Abdominal subcutaneous adipose tissue lipolysis at rest was increased with LCZ696 compared to AML (interstitial glycerol concentrations at week 8; 80.5 μmol/L vs. 64.0 μmol/L; p=0.020). The apparent exercise-induced increase in adipose tissue lipolysis was more pronounced with LCZ696 compared to AML at 15 and 30 min of exercise (interstitial glycerol concentrations at week 8; 15 min exercise: 153.1 μmol/L vs. 128.8 μmol/L, p=0.014; 30 min exercise: 187.63 μmol/L vs. 149.19 μmol/L, p=0.010). However, whole-body lipolysis at rest and during exercise was not significantly different between groups. While respiratory quotient increased with exercise in both treatment groups, energy expenditure and substrate oxidation at rest and during exercise did not differ between treatments. In conclusion, 8 weeks of treatment with LCZ696 vs. AML increased lipid mobilization from abdominal subcutaneous adipose tissue at rest and during physical exercise in obese, hypertensive patients, while whole-body lipolysis and lipid oxidation remained unchanged. This study therefore suggests an improvement in lipid mobilization with LCZ696 and supports a central role of NPs in the crosstalk between human cardiovascular and metabolic regulation.
Abstract 15169: Echocardiographic Reference Values of the Aortic Root Dimensions in Elite Athletes
Authors: Boraita Araceli , Heras María Eugenia , Morales Francisco , de la Rosa Alejandro , Barriopedro María Isabel , Canda Alicia , Rabadán Manuel , Calderón Francisco J , Tuñon José
Published: April 2024

Introduction:
The diagnosis of aortic (Ao) disorders in athletes is complicated by the belief that prolonged and intense exercise training may induce Ao enlargement as a physiological response. There are few studies with a large population of elite athletes (EA) regarding the effects of training on the aorta (Ao). This study was designed to establish the physiological limits of Ao remodeling associated to exercise training.

Hypothesis:
Since exercise training in EA could induce Ao remodeling, normal Ao dimensions could be greater in EA than in the general population.

Method:
Cross-sectional study including 4,267 healthy Spanish EA. All of them completed subsequently a minimal follow-up of 4 years without developing any event that precluded them to continue in high competition. There were 1,520 women (age 20.3±5.4 y, BSA 1.65±0.18 m2, 7.7±4.3 years/training and 19.6±10.6 hours/day of training) and 2,742 men (age 22.2±6.2 y, BSA 1.93±0.22 m2, 8.6±5 years/training and 18.9±8.8 hours/day of training). They were categorized into 3 groups according to the dynamic component of Mitchell`s classification (A=Low, B=Moderate, and C=High) and underwent transthoracic echocardiography. The end-diastolic Ao diameters were measured in the parasternal long axis at Ao annulus (AA), sinus of Valsalva (SV), sinotubular junction (SJ), and the maximum diameter of the proximal ascending Ao (Aspx).

Results:
Table 1 shows Ao measurements corrected by BSA, according to sex and dynamic component of the Mitchell`s classification (P95= percentile 95).

Two men had an Ao diameter greater than 40 mm at AA (0.1%), 38 at SV (1.8%), 3 at SJ (0.1%) and 6 at Aspx (0.3%). Fourteen women had an Ao diameter greater than 34 mm at SV (1.1%) and 2 at Aspx (0.1%).

Conclusions:
Mean diameters of Ao root in healthy EA are within the normal range for the general population both in absolute numbers and after correction for BSA at all levels of dynamic training. These values may be used as a reference to rule out Ao disease in EA.
Abstract 15201: Diastolic Pulmonary Gradient and Outcomes in Group 1 Pulmonary Hypertension (Analysis of the NIH Primary Pulmonary Hypertension Registry)
Authors: Mazimba Sula , Mejia-Lopez Eliany , Kennedy Jamie L , Bergin James , Tallaj Jose A , Gay Elizabeth , Abuannadi Mohammad , Mihalek Andrew D , Bilchick Kenneth C
Published: April 2024

Introduction:
The National Institute of Health (NIH) registry for primary pulmonary hypertension (PPH) established prognostic factors for PPH (now WHO group 1 PH). Diastolic pulmonary gradient {(DPG), Pulmonary artery diastolic pressure-mean Pulmonary capillary wedge pressure} ≥ 7 mmHg is associated with pulmonary vascular disease and a poor prognosis in heart failure (HF). The prognostic relevance of DPG in group 1 PH is uncertain.

Methods:
Using the NIH risk stratification equation for 239 patients in the NIH-PPH registry, the 5-year probability of death was calculated. The NIH model was then compared with DPG using a Cox proportional hazards model. Kaplan-Meier survival curves were determined for two cohorts using the median DPG of 30 mmHg as cutoff, and significance was tested using the logrank test.

Results:
The median age of patients was 38.1 ± 16.0 years old, 63% were female, and 72% had race reported as “white”. The mean DPG was 31.5 mmHg (± 13.6 mm Hg) and only 17.4% of patients had a DPG < 7 mm Hg. In a Cox proportional hazards model, increasing DPG was significantly associated with 5-year mortality even after adjustment for the NIH risk equation (DPG HR 1.18 per 10 mm Hg increase [95% CI 1.05-1.32]), and the chi square statistic for DPG compared favorably with the NIH risk equation (15.6 versus 26.2). When DPG was dichotomized based on the median value of 30 mm Hg, the hazard ratio for DPG > 30 mm Hg with respect to 5-year mortality was 1.91, 95% CI [1.34-2.75] (Figure). In a separate Cox model adjusted for pulmonary artery systolic pressure (PASP), increasing DPG remained significantly associated with decreased survival over 5 years (HR 1.45 for DPG > 30 mm Hg, 95% CI [1.01, 2.10]).

Conclusions:
DPG has higher distribution in PH than previously reported in HF studies and is associated with survival in group 1 PH patients even after adjustment for the NIH risk equation or PASP. More studies are needed to evaluate the use of DPG in guiding treatment and prognosis in group 1 PH.
Abstract 15209: Endotoxemia as Mechanism for Platelet Aggregation in Patients With Pneumonia
Authors: Nocella Cristina , Carnevale Roberto , Bartimoccia Simona , Pastori Daniele , Pignatelli Pasquale , Violi Franecesco
Published: April 2024

Introduction:
Patients with community-acquired pneumonia (CAP) are at increased risk of cardiovascular events; platelet activation has been suggested to play a role but the underlying mechanism is still unclear.

Hypothesis:
Our study hypothesis was that endotoxins (bacterial lipopolysaccharide, LPS) might play a role.

Methods:
Patients (n=100) with diagnosis of community-acquired pneumonia (CAP) through the emergency department (ED) and healty subjects (n=50) were consecutively recruited.

Categorical variables were reported as counts (percentage) and continuous variables as means ± standard deviation (SD).

The study was comprised 3 parts: 1) analysis of serum endotoxins in CAP patients versus controls; 2) ex vivo platelets aggregation in CAP patients and controls; 3) in vitro experiments to assess if LPS, in a range of concentrations detected in the blood of CAP patients, was capable of activating platelets.

Results:
CAP patients showed higher serum LPS and ex vivo platelet aggregation (PA) compared to controls. In in vitro study LPS, in a concentration (15-100 pg/ml) similar to that detected in human circulation of CAP patients, no changes of PA were detected. Conversely, LPS elicited PA if incubated with platelets stimulated with sub-threshold concentration of collagen or ADP; this effect was blunted in platelets pre-incubated with an inhibitor of toll-like receptor 4 (TLR4bp). LPS-mediated PA was associated with over-production of thromboxane (Tx) A2 and 8-iso-PGF2α-III, and was inhibited by aspirin or a TxA2 receptor antagonist. Platelet oxidative stress as assessed by measuring reactive oxygen species such as H
2
O
2
, and Nox2 activation was enhanced in LPS-treated platelets and reduced by the TLR4bp. Similarly, TLR4bp blunted the up-regulation of PLA2 phosphorylation, which was observed in LPS-treated platelets. Analysis of up-stream signaling potentially responsible for Nox2 and PLA2 activation demonstrated that LPS-mediated PA was associated with phosphorylation of AKT, p38 and p47
phox
translocation.

Conclusion:
Together these data show that LPS amplifies the platelet response to common agonists via TLR4-mediated eicosanoid production and suggest endotoxemia as a potential trigger for PA in patients with pneumonia.
Abstract 15284: Blessing in Disguise: Absent Pulmonary Valve in an Adult Without Ventricular Septal Defect
Authors: Arora Bhaskar , Upadhyay Shailendra , Toro-Salazar Olga , Gluck Jason , Sadiq Immad , Radojevic Joseph , Agarwal Arun , Skarzynski Kelly , Darsaklis Konstadina
Published: April 2024

Introduction:
Congenital absence of the pulmonary valve (APV) is a rare cardiac malformation. Adults with this condition generally need corrective surgery before the age of 20. We report a unique case of an isolated APV in a Jamaican female who remained asymptomatic until presentation at the age of 39.

Case:
Patient presented to a local cardiologist with recent onset of NYHA II symptoms and atrial fibrillation. Her cardiovascular exam revealed a right ventricular (RV) heave , III/VI holosystolic murmur along right lower sternal border, III/VI early diastolic murmur in pulmonic area, no clinical signs of right heart failure (RHF).

Diagnostics:
An echocardiogram showed dilated RV outflow tract, APV, dilated main pulmonary artery (MPA) and severe pulmonary regurgitation (PR) (Figure 1A). RV size and function were quantified with cardiac MRI demonstrating RV end diastolic volume: 340 ml/m2 (Z score 11.9) and RVEF: 46% ( Z score -2.8) (Figure 1B). Flow data of the MPA showed a flow of 4.9L/min, severe PR with a regurgitant fraction of 48% and Qp/Qs of 1.1:1 (Figure 1C). Right heart catheterization demonstrated equalization of diastolic pressure in both RV and PA (52/10 mm Hg) diagnostic of free PR. (Figure 1D). Mean PA pressure was 24 mm Hg and pulmonary vascular resistance was 3 wu. On cardiopulmonary stress testing, the patient completed 10.6 METS, achieving a peak VO2 of 18.5 ml/kg/min at RER 1.1.

Discussion:
APV is commonly categorized as with or without ventricular septal defect (VSD). APV with VSD is commonly associated with tetralogy of Fallot (TOF). The distinguishing features from TOF are: unobstructed RV infundibulum and aneurysmally dilated PA. APV in its severe form presents in infancy with severe respiratory distress from bronchial obstruction caused by massively dilated PAs. Isolated APV (non VSD type) is a rare variant.

Our report is the first in literature to illustrate isolated APV in an asymptomatic adult approaching the fourth decade of her life.
Abstract 15311: Anomaly and Narrowing of Radial Artery and its Impact to the Transradial Angiography and Intervention
Authors: Muta Yumiko , Watanabe Shigeyuki , Toyama Masahiro , Ojima Eiji , Kuroda Yasuhisa , Oishi Yuta , Aonuma Kazutaka
Published: April 2024

[Background]
Increasing number of transradial coronary procedures are now performed because of the advantage of reduced access site complications. However, transradial approach sometimes ends in failure or vascular complication due to arterial anomaly or stenosis.

[Objective]
The objective of this study was to clarify the types and frequency of radial or brachial arterial anomaly and narrowing in patients who undergone cardiac catheterization.

[Methods]
Total of 1135 consecutive patients who underwent transradial cardiac angiography or intervention from Jan. 2013 to May 2015 were subjected. In all cases, angiography of radial and brachial arteries was performed through the inserted sheath. After removing the duplicating cases, we analyzed 826 arms of 786 patients.

[Results]
Of total 826 angiographies, 622 were identified as normal. There were 20 (2.4%) cases of 'high-bifurcation' in which radial artery originates proximal of the intercondylar line of the humerus. 'Radial loop' with a full 360 degree loop of the radial artery and accompanied by the recurrent artery which originates at the loop was identified in 9 (1.1%) cases. 'Radial simple loop' and 'brachial simple loop' with a full 360 degree loop without recurrent artery were observed in 5 (0.6%) and 6 (0.7%) cases, respectively. 'Radial or brachial tortuosity' with a bend of more than 90 degree existed in 64 (7.7%) and 45 (5.4%) cases, and 'narrow radial or brachial' with the vessel diameter <2.0mm in 113 (13.7%) and 5 (0.6%) cases (some cases were duplicated). In high bifurcation, loop, or tortuosity cases, narrowing of the vessels of catheter route also coexisted in 20-89% cases. Cardiac catheterization ended in failure in 7 (1.1%) of normal radial and brachial artery cases, and in 31 (11.6%) cases of radial or brachial arterial abnormalities (p<0.0001). Among the 31 failure cases with radial or brachial artery abnormalities, the cause of the failure was narrowing of a catheter route in 24 (77%) cases, and 1 case with both radial tortuosity and narrowing ended in radial artery perforation.

[Conclusion]
Radial artery anomaly and narrowing are not infrequent and often coexist, and lead to procedure failure or even vascular complications, indicating a need of confirmation of vascular anatomy by angiography.
Abstract 15342: Does Ivabradine Affect Sympathetic Overdrive and Arterial Stiffening in Hypertensive Patients With Metabolic Syndrome?
Authors: Dimitriadis K. , Tsioufis C. , Koutra E. , Kalos T. , Liatakis I. , Andrikou E. , Vasileiou P. , Andrikou I. , Tousoulis D.
Published: April 2024

Introduction:
Hypertension and metabolic syndrome are related to sympathetic overdrive and arterial stiffening, while there are no data whether ivabradine modulates sympathetic activity and vascular abnormalities in this setting.

Hypothesis:
To assess the effect of ivabradine on muscle sympathetic nerve activity (MSNA) and arterial stiffness in hypertensive patients with metabolic syndrome.

Methods:
We studied 36 patients with essential hypertension [age: 56±10 years, 30 males, office blood pressure (BP): 148/92±14/11 mmHg] on antihypertensive therapy with a fixed combination of perindopril/amlodipine. Patients were randomized with a ratio 2:1 to ivabradine (5 mg twice daily) or no ivabradine (control group). Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. In all participants at baseline and at 6 months follow-up arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV) while sympathetic drive was assessed by MSNA estimations based on established methodology (microneurography).

Results:
Patients on ivabradine (n=24) compared to controls (n=12) did not differ regarding baseline BP, creatinine, glucose and lipid profile (p=NS or all). There was no significant difference in the reduction of office BP between the two study groups (p=NS). However, hypertensive patients in the ivabradine group were characterized by a reduction in carotid to femoral PWV from 11.5±0.9 m/sec to 9.8±1.2 m/sec (p<0.001) and sympathetic nerve traffic as reflected by MSNA levels from 86.2±2.5 bursts per 100 heart beats to 74.8±2.4 bursts per 100 heart beats (p<0.001) at 6 months. No significant changes in PWV and MSNA were observed in the control group (p=NS).

Conclusions:
In hypertensive patients with metabolic syndrome, treatment with ivabradine reduces sympathetic activation and arterial stiffening as reflected by lower MSNA and PWV levels at 6 months follow-up. These findings suggest that ivabradine could exhibit additional therapeutic properties in the setting of dysmetabolic hypertension.
Abstract 15539: A Novel Compound Tanshinol Prolongs Cardiac Allograft Survival Induced by Rapamycin
Authors: Dai Zhen H , Zhou Anyu
Published: April 2024

Introduction:
Cardiac transplantation provides a cure for end-stage heart diseases. Achieving long-term cardiac allograft survival without continuously global immunosuppression is a highly desirable goal because long-term immunosuppression causes serious side effects. This study is to induce long-term cardiac allograft survival without long-term conventional immunosuppression via treatments with Tanshinol, a major compound derived from traditional Chinese medicine, Danshen, which has been shown to improve tissue microcirculation and reduce inflammation.

Hypothesis:
Tanshinol alone, or in combination with mTOR inhibitor rapamycin, prolongs cardiac allograft survival.

Methods:
In this study, C57BL/6 mice were transplanted with a Balb/C heart and treated with Tanshinol (5mg/kg/day i.p. on days 0, 2, 4, 6, 8, 10 and 14) and/or rapamycin (1 mg/kg/day for 3 weeks). In vivo CD4+FoxP3+ Treg numbers from draining LNs and graft-infiltrating cells were quantified by FACS 3 weeks after transplantation.

Results:
We found that Tanshinol alone did not extend cardiac allograft survival compared to control group (MST = 8 vs. 7 days, n=7-8) while rapamycin delayed the rejection significantly (MST = 28 vs. 7 days, n=6-7, P<0.05). Interestingly, treatments with both Tanshinol and rapamycin further prolonged allograft survival (MST = 63 versus 28 days, n=7-8, P<0.05). Moreover, Tanshinol did not increase CD4+FoxP3+ Treg numbers in draining LN (DLN) (2.5±0.4 vs 2.2±0.3, x10000, P>0.05) while rapamycin did so (3.9±0.5 vs 2.2±0.3, P<0.05). In contrast, Tanshinol increased Treg number in grafts (13.5±0.9 vs 7.4±0.6, P<0.05) while rapamycin did not (8.1±0.7 vs 7.4±0.6, P>0.05). Tanshinol plus rapamycin augmented Treg numbers in both DLNs and grafts compared to untreated group. Thus, our studies reveal that Tanshinol and rapamycin synergistically prolong cardiac allograft survival without long-term immunosuppression by promoting Treg generation and migration to LNs and allografts.

Conclusion:
Our data, for the first time, demonstrate that Tanshinol synergizes with rapamycin to prolong cardiac allograft survival via enhancing both generation and migration of Tregs.
Abstract 15543: Increased Local Hepcidin Expression With Subsequent Degradation Of Ferroportin-1 is Associated With Iron Accumulation in the Aged Brain
Authors: Sato Tatsuya , Bayeva Marina , Khechaduri Arineh , Chang Hsiang-Chun , Ardehali Hossein
Published: April 2024

Background:
Age is a major risk factor for a number of neurodegenerative disorders, including Parkinson’s and Alzheimer’s disease. Several studies have shown that neurodegenerative disorders are sometimes associated with iron accumulation in the brain. Iron is an essential trace metal, however, excess iron can cause cellular damage due to increased oxidative stress and thus promote aging, yet how and why iron accumulates in the aged brain is unclear. The goal of this study is to delineate the mechanism of iron accumulation in the brain with aging.

Results:
We assessed the levels of iron in various tissues of aged mice (defined as 22 months old) vs young mice (defined as 4 months old). We found that non-heme iron was preferentially increased in the brain tissue of aged mice, while the levels were unaltered in other tissues. This was associated with increased ferritin (iron storage protein) levels in the brain, consistent with iron accumulation. To study the mechanism, we measured the mRNA levels of various proteins involved in iron homeostasis, and determined that the levels of hepcidin (HAMP) and tranferrin receptor-2 were increased in the brains, but not in the livers, of aged mice. HAMP is generally produced in the liver and functions to reduce intestinal iron uptake through degradation of basolateral iron exporter ferroportin-1 (FPN1), thus reducing systemic iron levels. However, HAMP is also detected in other tissues, such as the brain and the heart, where its function is less clear. To determine whether the increase in HAMP in the brain affects iron homeostasis, we measured the levels of FPN1 in the brain and showed that while its mRNA level was not altered, the protein level of FPN1 was significantly reduced in aged mice. Thus, the increase in HAMP in aged mice was associated with a reduction in FPN1 levels and iron accumulation in the brain, likely through reduced iron export from neurons and glial cells.

Conclusions:
Our results demonstrate that iron levels are significantly increased in the brain with aging. This increase is due to higher levels of HAMP protein, with subsequent degradation of iron exporter FPN1 and cellular iron accumulation secondary to defective export. Thus, targeting HAMP may lead to novel therapies for age-related neurodegenerative disorders.
Abstract 15562: Loss of Mitochondrial Pyruvate Carrier 1 in Cardiomyocytes Leads to Cardiac Dysfunction and Heart Failure via Hif-1 Activation
Authors: Zhang Yuan , Cox James , Rutter Jared , Abel E. Dale
Published: April 2024

Glucose and lactate are important fuel substrates for the heart, particularly during acute hemodynamic stresses such as pressure overload or following exercise training. Cytosolic pyruvate that is generated by glycolytic metabolism of glucose or by conversion of lactate is transported into mitochondria via the recently described mitochondrial pyruvate carrier complex, which has two subunits, MPC1 and MPC2. The role of pyruvate uptake in regulating cardiac function and metabolism is incompletely understood. Thus, we generated cardiomyocyte-restricted MPC1 knockout mice (CMPC1-/-). Loss of MPC1 resulted in degradation of MPC2 leading to functional inactivation of the MPC complex in CMPC1-/- mouse hearts. Cardiac function examined by echocardiography revealed that CMPC1-/- mice exhibited normal cardiac function by the age of 8 weeks but overt systolic dysfunction was noted at the age of 18 weeks. Survival analysis showed that only 61% of CMPC1-/- mice remained alive at the age of 1year while 98% of control mice survived. At the age of 8 weeks, heart weight (HW) and the heart weight to tibia ratio (HW/TL) were significantly increased, as were characteristic transcriptional markers of pathological cardiac hypertrophy, NPPA, NPPB and Acta1. Substrate metabolism measured in isolated working hearts, revealed a 58% reduction in glucose oxidation in CMPC1-/- mice relative to control mice while palmitate oxidation was increased by 35%. Metabolomics analyses revealed accumulation of pyruvate, lactate and alanine. In contrast, malate and glutamate levels were decreased, suggesting a compensatory increase in malate and glutamate utilization. 2-hydroxyglutarate (2-HG) was also increased in CMPC1-/- mouse hearts, which may activate Hif-1α signaling. Indeed, downstream transcriptional targets of Hif-1 (LDHA, PDK1 and PKM2) were increased. These data suggest that mitochondrial pyruvate uptake although dispensable for normal cardiac development and function in non-stressed juvenile hearts ultimately precipitates pathological cardiac hypertrophy and heart failure in CMPC1-/- mice via 2-HG-mediated Hif-1 activation.
Abstract 15625: Flecainide Modulates Action Potential Properties of Cardiac Sympathetic Neurons
Authors: Tsai Wen-Chin , Chen Peng-Sheng , Rubart-von der Lohe Michael
Published: April 2024

Introduction:
Sympathetic nerve activity is important in the genesis of catecholaminergic polymorphic ventricular tachycardia (CPVT). Flecainide is effective in managing patients with CPVT.

Hypothesis:
We hypothesize that flecainide in clinically relevant concentrations alters electrical properties of cardiac sympathetic nerves.

Methods:
We used the perforated-patch technique in current-clamp mode to record action potentials from single sympathetic neurons isolated from stellate and superior cervical ganglia of ∼2-month-old mice. Action potentials in response to current pulses (10 ms, 0.05 to 0.2 nA, 0.2 Hz) were acquired in control, 1, 5, 10 μM flecainide, and wash out.

Results:
Flecainide dose-dependently decreased action potential amplitude (in mV, medians with 25 and 75% percentiles) from 131.6 [127.0 - 138.0; control] to 131.1 [123.7 - 137.5; 1 μM], 128.9 [120.0 - 134.4; 5 μM] and 126.1 [115.9 - 132.6; 10 μM
; P
< 0.05 by Repeated Measures ANOVA], and upstroke dV/dt
max
(in V/s) from 172 [109 - 216; control] to 158 [110 - 198; 1 μM), 109 [98 - 174; 5 μM) and 92 [84 - 147; 10 μM;
P
< 0.05]. Action potential duration at 50% repolarization was significantly prolonged at 10 μM flecainide (
P
< 0.05). The changes were reversible upon washout. Resting membrane potential was unaltered. The Figure shows representative action potentials for control and 10 μM flecainide.

Conclusions:
Flecainide-induced changes in action potential properties are compatible with inhibition of neuron-type voltage-gated Na
+
channels and K
+
channels. These actions may decrease sympathetic excitability on the heart, thus help control CPVT.
Abstract 15704: Exploratory Analysis of the Efficacy of β-blockersin Patients With Post-infarction Systolic Dysfunction Plus Atrial Fibrillation
Authors: González Salvado Violeta , Raposeiras Roubín Sergio , Ariza-Solé Albert , Abu-Assi Emad , Muntané Guillem , Garay Alberto , Varela Román Alfonso , González-Juanatey José Ramón
Published: April 2024

Introduction:
β blocker therapy for patients with acute myocardial infarction (AMI) and reduced left ventricular ejection fraction (LVEF) was instituted after large randomized controlled trials showed a significant reduction in morbidity and mortality rates. Recently, their efficacy in patients with heart failure (HF) and atrial fibrillation (AF) has been questioned, based on the results of a large meta-analysis. We aim to analyze the efficacy of β blocker therapy in patients with post-AMI reduced LVEF and permanent AF.

Methods:
We studied all consecutive patients discharged with AMI and LVEF ≤ 40% from Hospital of Santiago de Compostela (2004-12) and Bellvitge Hospital of Barcelona (2009-14). The final cohort included 1,056 patients after excluding those without follow-up data. We analyzed the association between β blockers and follow-up (3.0 ± 2.5 years) mortality using Cox regression, adjusting by all confounding variables and by propensity score.

Results:
782 patients (74.6%) were treated with β blockers. There were prescribed to 67.1% of patients in sinus rhythm (SR) and to 71.4% in AF. 140 patients (13.2%) had permanent AF at discharge.

In SR group, β blockers were associated with lower mortality during follow-up (HR 0.42, 95% CI 0.31-0.53; p<0.001) after adjusting by the confounding variables (HR 0.50, 95% CI 0.32-0.96; p=0.028) and by propensity score (HR 0.68, 95% CI 0.51-0.92; p=0.010), but not in the AF group (HR 0.75, 95% CI 0.45-1.23; P=0.248) after adjusting by the confouding variables (HR 0.67, 95% CI 0.34-1.32; p=0.247) and propensity score (HR 0.81, 95% CI 0.47-1.40; p=0.459).

Conclusion:
β blocker therapy has no or minimal effect on mortality in patients with post-infarction reduced LVEF and AF, in contrast with its beneficial effects in SR. Thus, we call into question the preferential use of β blockers compared with other rate-control drugs in these patients (1A) and we emphasize the need for further trials to clarify it.
Abstract 15770: Sex Differences in Growth Rates of Thoracic Aortic Aneurysms
Authors: Cheung Katie , Boodhwani Munir , Chan Kwan-Leung , Beauchesne Luc , Dick Alexander , Coutinho Thais
Published: April 2024

Introduction:
Thoracic aortic aneurysm (TAA) is a deadly disease of increasing prevalence. Although more prevalent in men, TAA-related mortality is higher in women. In addition, women develop acute aortic syndromes at smaller aneurysm diameters, independently of body size. However, the basis for worse TAA outcomes in women is unknown. Since faster TAA growth is an established risk factor for acute aortic syndromes, we sought to determine the role of sex on TAA growth.

Hypothesis:
We hypothesized that TAA growth rates differ based on sex.

Methods:
Fifty three consecutive unoperated subjects with TAA who had serial aneurysm measurements by CT, MRI or echocardiography were prospectively recruited. Aneurysm size was measured systematically by an imaging cardiologist (TC); growth rate was calculated as mm/year. In multivariable linear regression, the association of female sex with aneurysm growth rate was assessed after adjustment for age, and then additional adjustment for body surface area, baseline aneurysm size, beta-blocker use and history of hypertension, diabetes, dyslipidemia and smoking.

Results:
Thirty seven (70%) subjects were men; mean±SD age was 63.7±11.9 years (62.2±12.3 in men, 66.9±10.6 in women,
P
=0.17). Thirty (57%) subjects had degenerative TAAs, the remainder had heritable TAAs. Fifteen had maximal dilation at the aortic root, and 38 at the ascending aorta. Baseline aneurysm size and follow-up time were 45.4±4.5 mm and 3.01±2.9 years, respectively, and not different between men and women (
P
>0.05 for both). Aneurysm growth rate was 1.22±1.09 mm/year in women and 0.68±0.68 mm/year in men. Female sex was significantly associated with greater aneurysm growth rate after adjustment for age (β±SE: 0.25±0.13,
P
=0.05) and additional adjustment for confounders (β±SE: 0.30±0.14,
P
=0.03). Notably, baseline aneurysm size was not associated with TAA growth (β±SE: -0.01±0.0.03,
P
=0.72).

Conclusions:
In subjects with TAA from different etiologies, reflecting clinical practice, aneurysm growth rates are greater in women than men. Our findings may potentially explain sex differences in TAA outcomes, providing a foundation for future investigations aimed at assessing causes for faster aneurysm growth and acute aortic syndromes in women.
Abstract 15795: Prevalence and Characteristics of Left Ventricular Fibrosis in Patients With Mitral Valve Prolapse
Authors: Kitkungvan Danai , Nabi Faisal , Quinones Miguel , Xu Jiaqiong , Lawrie Gerald , Little Stephen H , Zoghbi William , Shah Dipan J
Published: April 2024

Introduction:
Studies have suggested a link between mitral valve prolapse (MVP) and arrhythmia/sudden cardiac arrest. LV fibrosis is potentially an arrhythmia substrate. Late gadolinium enhancement (LGE) CMR is established for detection of LV fibrosis. We evaluated for LV fibrosis in MVP patients using LGE-CMR.

Method:
Consecutive patients with primary MR undergoing CMR were enrolled, and classified as MVP or non-MVP etiology. We excluded secondary MR and confounding etiologies of LV fibrosis (e.g. CAD, significant LVH). All underwent cine-CMR to assess cardiac morphology/function, phase contrast CMR to quantify MR, and LGE-CMR 10 minutes after gadolinium to identify LV fibrosis.

Result:
Among 356 patients with primary MR, MVP was present in 177 (49.7%). Overall, LV fibrosis occurred in 83 patients (23.3%) in which mid-wall striae was the most common LGE pattern (54.2%), mean LGE burden 2.2% ± 0.9% of LV. LGE was more prevalent in patients with MVP (37.9% vs. 8.9%, p < 0.001), most common in the basal inferolateral wall (31.1%). Although prevalence of LGE increased with MR severity, it was more prevalent in MVP patients for any given severity of MR (figure 1). After adjusting for clinical and imaging variables including severity of MR, MVP was associated with finding of LGE (OR = 4.5, 95% CI of 2.3-8.7, p < 0.001) and LGE in the basal-mid inferolateral and basal inferior wall (OR of 39.4, 95% CI of 9.0-172.6, p < 0.001).

Conclusion:
In primary MR, LV fibrosis, a potential substrate for arrhythmias, was more prevalent in MVP patients irrespective of severity of MR or other clinical/imaging variables. These findings suggest a unique pathophysiology of MVP beyond valvular regurgitation alone.