bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9116: Overlap Between Cognitive Brain Damage and Reduced Cerebral Blood Flow in Heart Failure
Authors: Woo Mary A , Kumar Rajesh , Fonarow Gregg C
Published: April 2024

Heart failure (HF) subjects show reduced cerebral blood flow (CBF) in brain sites that control autonomic and cognitive functions. Brain structural injury also emerges in cognitive and autonomic control sites; however, it is unclear whether brain sites with reduced CBF overlap areas with structural brain injury.

METHODS:
We collected Diffusion Tensor Imaging (DTI) data from 9 HF (age, 54.6±10.4 years; BMI, 30.5±5.4 kg/m2; LVEF, 31.3±7.8, 6 male) and 7 control subjects (age, 53.7±3.1 years; BMI, 25.9±3.0 kg/m2, 6 male) using a 3.0 Tesla MRI scanner, and assessed regional brain injury and overlap with CBF changes. Using DTI data, whole brain mean diffusivity (MD) maps were calculated, normalized to a common space, and smoothed. The normalized and smoothed MD maps were compared voxel-by-voxel between HF and controls using ANCOVA (p = 0.005), with age and gender as covariates. The brain clusters with significantly increased MD values, indicative of brain injury, were overlaid onto background images. The brain clusters with significantly reduced regional CBF values were also overlaid onto background images. Both findings were compared region-by-region for overlap in structural injury and CBF changes.

RESULTS:
Multiple brain areas in HF subjects (Figure), including the right insular lobe (a), right hippocampus (b), and midline pons (c) showed overlap in structural injury and CBF changes (ANCOVA p=0.005; group comparisons in Table).

CONCLUSIONS:
HF subjects show brain sites with overlap in structural injury and CBF changes in autonomic and cognitive regulatory areas. The findings indicate that reduced CBF may contribute to structural injury in those sites.
Abstract 9132: Balloon Aortic Valvuloplasty Performed Without Heparin is Associated with a Reduction in Vascular and Bleeding Complications rates
Authors: LeClercq Florence , Delseny Delphine , Nogues Erika , Nagot Nicolas , Macia Jean christophe , Gervasoni Richard , Piot Christophe , Roubille FranÇois
Published: April 2024

Objectives: Bleeding and vascular complications are currently the main adverse events associated with balloon aortic valvuloplasty (BAV). We assessed the hypothesis that BAV performed without heparin may be associated with lower complication rates. Methods We conducted a retrospective analysis of all consecutive patients who had undergone BAV in our center between 2008 and 2011. We evaluated 3 groups: patients included between 2008 and 2009 when BAV was performed with large sheaths (10 to 12 French) and injection of unfractionated heparin (UH) (50IU/kg bolus IV) (group 1); patients included after 2009, for whom smaller size sheaths (8 or 9 French) were used, were divided into 2 groups: group 2 (with UH bolus) and group 3 (without UH bolus). We collected all major in-hospital adverse events, bleeding (≥ BARC 3), vascular access complications (including pseudoanerysm or arterio venous fistula) and acute limb ischemia. Results Overall, 140 patients were included in this study. The 3 groups had similar median age (84 years) and preceding lower extremity artery disease (overall n= 36, 27%, p=0.79). Vascular access and bleeding complications were observed in 16 patients (11.4%) and were lower in group 3 compared to group 1 and group 2 (table 1). The use of heparin was associated with an increased risk of vascular access and bleeding complications [relative risk (IC) 2.85 (1.28 to 9.13] whereas absence of heparin did not increase ischemic complications as acute limb ischemia (p=0.82), stroke (1 patient in group 2) or other major in- hospital adverse events (p=0.5). Vascular and bleeding complications were comparable among patients who received heparin with no influence of the used sheath’ s size (table 1). In conclusion, we showed in this study that balloon aortic valvuloplasty performed without heparin is safe and leads to a dramatic reduction of vascular and bleeding events. Although randomization was not used, this marked difference is difficult to explain by confounding factors. .
Abstract 9140: The Majority of Plakophilin-2 Mutations in Arrhythmogenic Cardiomyopathy are Associated with Haploinsufficiency in the Myocardium and Epidermis
Authors: Rasmussen Torsten B , Nissen Peter H , Palmfeldt Johan , Gehmlich Katja , Dalager Søren , Jensen Uffe B , Kim Won Y , Heickendorff Lene , Mølgaard Henning , Jensen Henrik K , Baandrup Ulrik T , Bross Peter , Mogensen Jens
Published: April 2024

Background:
Arrhythmogenic cardiomyopathy (AC) is a hereditary cardiac condition associated with ventricular arrhythmias, heart failure and sudden death. The disease is most often caused by mutations in the desmosomal gene for plakophilin-2 (PKP2), which is expressed in both myocardial and epidermal tissue. It was the aim of this study to investigate protein expression in myocardial tissue of ARVC patients carrying PKP2 mutations and elucidate if keratinocytes of the same individuals exhibited a similar pattern of protein expression.

Methods and Results:
Direct sequencing of 5 ARVC-genes in 71 unrelated ARVC patients identified 10 different PKP2 mutations. One patient, a digenic carrier of heterozygous PKP2- and desmoglein-2 mutations, developed severe heart failure and underwent cardiac transplantation. Western blotting and immunohistochemistry of the explanted heart showed a significant decrease in PKP2 protein expression without detectable amounts of truncated PKP2 protein. Cultured keratinocytes of the patient showed a similar reduction in PKP2 protein expression. Nine additional PKP2 mutations were investigated in both cultured keratinocytes and endomyocardial biopsies from affected individuals. It was evident that PKP2 mutations introducing a premature termination codon in the reading frame were associated with reduced PKP2 transcript and protein levels while a missense variant did not affect PKP2 expression levels.

Conclusion:
This study indicated that the majority of PKP2 mutations in ARVC are associated with haploinsufficiency. Furthermore, myocardial PKP2 expression in mutation carriers correlate well with PKP2 expression in keratinocytes of the same individuals. This finding makes keratinocyte cultures a promising new tool to characterize desmosomal protein expression in AC patients. Figure legend: A) The explanted heart of a digenic mutation carrier with AC, B) Western blotting of PKP2, C) Western blotting of DSG2
Abstract 9142: Performance of Synergraft Decellularized Pulmonary Allografts Compared With Standard Cryopreserved Allografts: Results from Multi-Institutional Data
Authors: Bibevski Steven , Wilkinson David A , Ruzmetov Mark , Fortuna Randall , Turrentine Mark , Brown John W , Ohye Richard G
Published: April 2024

Objectives: Cryopreserved pulmonary allografts frequently demonstrate early valve failure and structural degeneration believed to be related in part to an immune response mounted against HLA specific to the transplanted tissue. SynerGraft processing (CryoLife Inc., Kinnesaw, GA) decellularizes the allograft and therefore reduces its immunogenicity. Previous data comparing standard allograft to SynerGraft has been from single institutions and included limited numbers of patients. The purpose of this project was to assess the durability of the SynerGraft-processed allografts compared with standard cryopreserved allografts using data from multiple institutions.

Methods: A multi-institutional review was performed of all CryoValves implanted between 2001 and 2010. One hundred sixty-three SynerGraft patients and 124 standard allograft controls were evaluated. Demographics, survival, reintervention, and echocardiographic findings were analyzed.

Results: Mean age (months) was 208 ± 198 versus 151 ± 172 (p=N.S.), mean weight (kg) was 45 ± 36 versus 35 ± 33 (p=0.12), and mean valve diameter (mm) was 22.1 ± 5.8 versus 19.5 ± 6.1 (p=<0.05), for SynerGraft and standard allografts, respectively. At a mean echo follow up (months) of 60 ± 34 versus 59 ± 35, mean gradient (mm Hg) was 20.7 ± 15.7 versus 27.3 ± 18.8 mmHg for the (p<0.05). Mean insufficiency grade (0-4) at last follow-up was 1.8 for SynerGraft and 2.3 for standard allograft (p<0.001), and for patients under the age of 24 months was 2.4 for SynerGraft and 3.2 for the standard allograft (p=0.01). By Kaplan-Meier analysis, 8-year freedom from reintervention was 82% for SynerGraft and 60% for the standard allograft (p=0.001). Eight-year freedom from insufficiency was 76% for SynerGraft and 47% for the standard allograft (p<0.001). There was no statistically significant difference in survival.

Conclusions: When compared to standard allografts, SynerGrafts demonstrate superior freedom from significant insufficiency and stenosis at a similar follow up period with lower rates of need for reintervention.
Abstract 9143: Mortality Resulting From Congenital Heart Diseases Through 2003 To 2010: A Population-based Study In China
Authors: Hu Zhan , Yuan Xin , Krumholz Samuel , Zheng Zhe , Hu Shengshou
Published: April 2024

BACKGROUND:
Previous studies suggested that mortality from congenital heart diseases (CHD) is declining in the US. But we don't know what the CHD mortality trend is in China. What's more, we don't know whether the trends in rural and urban region follow different pattern or not in China, the largest developing country with rapid urbanization. This study aimed to determine recent changes in death caused by CHD in China and describe CHD mortality in rural and urban Chinese populations.

METHODS:
The data source was the China Ministry of Health 2003-2010 annual reports. Mortality was defined as death caused by CHD. Mortality rates for each year were calculated per 100,000 person-years. Poisson regression and descriptive analysis were conducted for overall trend and sub-group analysis was conducted by gender, age and urban/rural to understand potential disparities in mortality.

RESULTS:
From 2003-2010, the overall mortality rate increased from 141 per 100,000 person-years in 2003 to 229 in 2010, a 62.4% relative increase. This represents a region-sex adjusted annual increase of 9% (incidence rate ratio, 1.09; 95% CI, 1.09 to 1.10). The increase in CHD mortality was not uniformly observed across age groups, urban/rural and gender. The relative increases were 65.3%, 212.2% and 131.7% for age 1-10, 21-64 and 65 or older groups, respectively. Urban areas had a relative increase of 154.5% vs. 5.3% for rural areas. Female who lived in an urban environment had a relative increase of 313.5%.

CONCLUSION:
Different from US where the CHD mortality is reducing, our observation, based on Chinese Ministry of Health 2003-2010 annual reports, showed an obvious increasing trend of CHD mortality in China. What's more, increase in CHD mortality was not uniformly observed across age groups, urban/rural and gender. Such information is needed as a basis for working out and evaluating interventions and for the ongoing monitoring of CHD mortality and allocation of healthcare resources to properly treat CHD patients.
Abstract 9253: Proteomic and Functional Assessment of High Density Lipoprotein Subclasses in Acute Coronary Syndromes Subjects as Well as Control Subjects
Authors: Tan Ying , Liu Ting-Rong , Hu Shui-Wang , Tian Di , Guo Zhi-Gang
Published: April 2024

Objectives:
To explicit whether the functions of HDL subclasses (HDL
2
and HDL
3
) are impaired in subjects with acute coronary syndromes (ACS). And on top of that, we confirm that alterations in HDL subclasses proteomics may exert an instrumental effect on the occurence of dysfunctional HDL subclasses.

Methods:
We measured HDL subclasses inflammatory index (HII), paraoxonase (PON) activity and LOOH levels in 30 patients with ACS compared with 30 healthy subjects. Additionally, proteomics was used to monitor changes in the HDL subclasses proteome between controls and ACS subjects. HDL subfractions were isolated by ultracentrifugation and the proteins were separated with 2-D gel electrophoresis and identified with mass spectrometry.

Results:
Subjects with ACS had higher HII and HDL-LOOH levels compared with controls; Paraoxonase activity in ACS group was significantly lower than that of control group (Table 1). Using proteome analysis, we demonstrated that compared with control group, HDL
3
from subjects with ACS was selectively enriched in 8 proteins (apoA-I, apoA-IV, apoE, apoL1, PON, alpha-1B-glycoprotein, amyloid P-component, fibrinogen gamma chain), and meanwhile ras-related protein Rab-7b was decreased in HDL
3
. Moreover, HDL
2
from ACS group was selectively lower in 10 proteins (apoE, PON, apoA-IV, apoL1, haptoglobin, hemopexin, serotransferrin, complement factorB, fibrinogen gamma chain,ras-related protein Rab-7b); but 2 proteins were increased in HDL
2
(amyloid P-component, alpha-1 antitrypsin).

Conclusions:
HDL subclasses have less anti-inflammatory and anti-oxidant capacities in ACS patients compared with controls. Moreover, the study also suggest that composition alteration of HDL subfractions may play a pivotal role in the progress of functional HDL subclasses shift to dysfunctional HDL subclasses. Furthermore, this research reveals new proteins in HDL
2
and HDL
3
; serum amyloid P-component and ras-related protein Rab-7b.
Abstract 9351: Left Ventricular Torsion is Preload Dependent. A Study in Healty Volunteers After Blood Donation
Authors: Kilic Harun , Saygısunar Ugur , Ayturk Mehmet , Vural Mustafa Gokhan , Akdemir Ramazan
Published: April 2024

Introduction:
Left ventricular (LV) rotation plays an important role in LV contraction and relaxation.

Hypothesis:
Aim of this study is to investigate preload effect on LV torsion in normal volunteers of blood donation.

Methods and Results:
LV end-diastolic volume, LV apical and basal rotation, peak systolic LV Torsion were measured by speckle-tracking echocardiography in normal volunteers (n=26) before and after 450ml blood donation.Blood donation led to a significant decrease in end-diastolic LV internal diameter (48.7 + 0.4 versus 46.4+0.4 mm; P<0.001) and cardiac output (6.2 + 1.0 versus 5.1+ 0.7 L/min; P<0.001). There was a significant decrease in the magnitude of peak systolic apical rotation (4.4 +1.9° versus 2.9 + 1.5°; P<0.001) but no change in basal rotation (2.6 +1.4° versus 2.7+ 1.6°; P=0.81). Peak systolic LV Torsion decreased after blood donation (6.9 +1.9 ° versus 5.7+2.1°; P=0.028).

Conclusions:
LV apical and peak systolic LV torsion are preload dependent. Preload changes should be considered when interpreting LV torsion
Abstract 9376: Maximum Dose of N-acetylcysteine and Prevention of Renal Dysfunction in Patients With Chronic Kidney Disease Undergone Surgical Coronary Intervention: A Prospective, Randomized, Double-blind, Controlled Trial
Authors: De Lima Jose J , Santos Eduesley S , Gowdak Luis Henrique W , Gaiotto Fabio , Puig Luiz B , Costa-Hong Valeria , Arantes Rodolfo L , César Luiz Antonio M , Bortolotto Luiz A
Published: April 2024

Background:
The role of N-acetylcysteine (NAC) for the prevention of renal damage in experimental models and in diverse clinical settings is controversial. Disparate results may be caused by differences in dosing and route administration. Objective: to test the safety and efficacy of maximum IV dose of NAC, as recommended for acetaminophen overdose, on the incidence of renal dysfunction, in 50 patients with GFR <60/≥15 ml/min (64±9 yo, Caucasians 80%, men 74%, diabetics 56%, comorbidities 90%, LVEF 54%±11%, GFR 45±11 ml/min, Euroscore 5.4%) undergone elective surgical coronary intervention (CI).

Methods:
patients were randomized to receive either IV saline (n=26) or NAC (n= 24) in equal volume of saline (150 mg/Kg followed by 50 mg/kg) during surgery. End-points: renal dysfunction (AKIN criteria), serum NGAL and TBARS during the first 72-h post-operation; need of dialysis and death within 30-days post-operation.

Results:
NAC was not associated with significant side-effects. There was one death in the NAC group (cardiac arrest) and none among controls and no patient needed dialysis. Base-line age, gender, race, diabetes, dyslipidemia, smoking, comorbidities, GFR, Euroscore, and number of grafts, on-pump surgery, transfusions, vasoactive drugs and diuresis (during and after operation) did not differ between groups. Renal dysfunction was observed in 64% (controls) and 27% (NAC) patients (p= 0.02) and no use of NAC was the only independent predictor of renal dysfunction (OR= 4.86, p=0.02). NGAL and TBARS were higher in patients not receiving NAC (=< 0.05).

Conclusion:
maximum IV dosing of NAC was well tolerated and was associated with reduction on the incidence of renal dysfunction in patients with CKD undergone surgical coronary intervention. More work is needed to determine the optimal dosing of NAC in this setting.
Abstract 9378: Glucose Fluctuations Aggravate the Vulnerability of Diabetic Heart Against Ischemia/reperfusion Mediated via microRNAs Modulation
Authors: Teshima Yasushi , Takahashi Naohiko , Thuc Luong Cong , Nishio Satoru , Saito Shotaro , Fukui Akira , Kume Osamu , Nakagawa Mikiko , Saikawa Tetsunori
Published: April 2024

[Objective]
Frequent hypoglycemia attack reportedly increased cardiovascular events and mortality in patients with diabetes mellitus (DM). In the present study, we investigated whether glucose fluctuations may increase the susceptibility to ischemia/reperfusion in diabetic rat heart and the involvement of microRNA (miRNA) as well.

[Methods and Results]
In
in vitro
experiments, cultured cardiomyocytes were alternately exposed to high (450 mg/dL) and low (30 mg/dL) concentrations of glucose for 5 days. Exposure to glucose fluctuations increased level of reactive oxygen species (ROS) and made cardiomyocytes more vulnerable to oxidative stress compared to sustained high glucose exposure. In
in vivo
experiments, rats were divided into 3 groups: control, DM, and DM with glucose fluctuations. DM was induced by intravenous injection of streptozotocin (60 mg/kg) and glucose fluctuation was induced by 24h-fasting and insulin injection (0.5 IU/kg). Isolated hearts were subjected to 20min global ischemia followed by 30min reperfusion. The infarct size was larger in diabetic hearts with glucose fluctuations than those with consecutive hyperglycemia. Electron microscopy disclosed that mitochondria were swollen and structure of cristae was destroyed in diabetic heart, and those changes were aggravated by glucose fluctuations. The level of ROS and activities of intracellular antioxidant enzymes were analyzed in search of possible mechanisms. Level of ROS was increased, and activities of catalase and superoxide dismutase were down-regulated in the heart with glucose fluctuations compared to sustained hyperglycemia. Further, microarray analysis was performed to explore the expression profiles of miRNAs in each group. Expressions of mir-200c and -141 were more abundant in the hearts exposed to glucose fluctuations than those with sustained high glucose level. We also confirmed that these miRNAs seem to contribute to the decreased activities of antioxidant enzymes and subsequent ROS increase.

[Conclusions]
Glucose fluctuations increased ROS level and enhanced ischemia/reperfusion injury in diabetic heart. Up-regulations of mir-200c and -141 may account for ROS increase by suppressing antioxidant enzymes.
Abstract 9398: Cornell Product Criteria for Left Ventricular Hypertrophy Strongly Predicts the Presence of Diastolic Dysfunction
Authors: Krepp Joseph M , Lin Fay , Min James K , Devereux Richard B , Okin Peter M
Published: April 2024

Background:
Abnormal left ventricular (LV) diastolic function is a known predictor of poor cardiovascular outcomes. Although ECG LV hypertrophy (LVH) has been related to LV systolic dysfunction and both prevalent and incident heart failure, whether ECG LVH is associated with LV diastolic dysfunction (DD) is unknown.

Methods:
From a cohort of patients who underwent both cardiac computed tomographic angiography and transthoracic echocardiography (TTE) with complete evaluation of diastolic function, 185 that underwent ECG within one year of TTE were identified as the study group. The presence of DD was determined according to standard guidelines via evaluation of mitral inflow velocities, tissue Doppler imaging, deceleration time, isovolumic relaxation time, pulmonary venous systolic: diastolic ratio, and left atrial enlargement. ECG LVH by Cornell product (CP) criteria was categorized into the highest quartile (≥1595 mm[[Unable to Display Character: ⋅]]ms) vs the lower three quartiles or evaluated as a continuous variable with odds ratios (OR) calculated for each SD of the mean (664 mm[[Unable to Display Character: ⋅]]ms) higher CP.

Results:
Among the 185 patients (56.2% female, mean age 54.6 ± 15.6), mean CP was 1240 ± 664 mm[[Unable to Display Character: ⋅]]ms and 105 (57%) had DD. In univariate logistic regression analysis, being in the upper quartile of CP was associated with over fivefold greater odds of DD (OR 5.1 95% CI 2.2-11.7, p<0.001). In alternative analyses treating CP as a continuous variable, each 1 SD increase in CP was associated with an OR of 1.9 for DD (95% CI 1.3-2.7 p<0.001). In multivariate logistic regression analyses adjusting for statistically significant univariate predictors of DD including age, history of hypertension, hypercholesterolemia, indexed LV mass, R wave axis, degree of coronary artery disease, PR interval and ST segment deviation as covariates, the highest quartile of CP remained associated with a significantly increased odds of having DD (OR 5.7 95% CI 2.2-14.7 p=0.001); alternatively, each 1 SD of CP was associated with a 1.8-fold increased odds of DD (95% CI 1.2-2.5 p=0.003).

Conclusions:
Cornell product ECG LVH is a powerful predictor of the presence of diastolic dysfunction, even after adjustment for potential confounding risk factors and ECG variables.
Abstract 9412: Vasopressin V2 Receptor Antagonist Tolvaptan Prevents The Development of Chronic Heart Failure via Its Anti-inflammatory and Anti-fibrotic Actions
Authors: Yamazaki Takanori , Izumi Yasukatsu , Nakamura Yasuhiro , Yamaguchi Takehiro , Hanatani Akihisa , Shimada Kenei , Iwao Hiroshi , Yoshiyama Minoru
Published: April 2024

Introduction:
Arginine vasopressin (AVP), which promotes the reabsorption of renal water via the AVP V2 receptor, is overexpressed in chronic heart failure (CHF). A non-peptide V2 receptor antagonist, tolvaptan (TLV), induces aquaresis without affecting electrolyte. A recent clinical study indicates that the TLV-treated patients had significantly lower rates of mortality or hospitalization for worsening heart failure than those administered the placebo. Hypothesis: TLV has more beneficial effects than furosemide (FRS), a loop diuretic, on CHF after myocardial infarction (MI).

Methods:
Ten weeks after MI induction, rats were divided into 3 groups (n=9-10) adjusted to the infarct size as determined by echocardiography: a vehicle group (V), a group treated with 15 mg/kg/day of FRS (F), a group treated with 10 mg/kg/day of TLV (T). Control rats were subjected to a sham operation, and each treatment agent was administered for four weeks. After treatment, we compared the effects of TLV with FRS in hemodynamics, cardiac function, inflammation, and fibrosis.

Results:
Although no significant intergroup differences were noted in the blood pressure, heart rate and infarct size, echocardiographic study revealed that both end-diastolic and systolic volumes in the T group was lower levels than those in the V group (P<0.01). The ejection fraction was also improved in the T group (p<0.05) but not in the F group, compared with the V group. TLV treatment significantly attenuated MI-induced interstitial fibrosis and macrophage infiltration in the marginal area of the infarct by sirius red staining and and ED-1 immunostaining (p<0.01, respectively), but FRS did not affect them. Compared with the V group, mRNA expressions of atrial natriuretic peptides, brain natriuretic peptides, monocyte chemotactic protein-1, and transforming growth factor-β1 were significantly attenuated in the marginal area of the T group (approximately 60%, 50%, 36%, and 35% decrease, p<0.05, respectively). In contrast, FRS failed to decrease the expressions.

Conclusions:
Tolvaptan may prevent cardiac remodeling in CHF. This effect may be attributed to its volume-reducing effect as well as its anti-inflammatory and anti-fibrotic actions.
Abstract 9439: Inhaled Iloprost Improves Exercise Function in Subjects after Fontan Palliation
Authors: Rhodes Jonathan , Ubeda-Tikkanen Ana , Clair Mathieu , Fernandes Susan M , Graham Dionne A , Daly Kevin , Mullen Mary P , Landzberg Michael J
Published: April 2024

Background:
The exercise capacity of pts who have had Fontan surgery is often depressed. We hypothesized that an inability to reduce pulmonary vascular resistance appropriately during exercise contributes to this exercise intolerance, and that administration of an effective pulmonary vasodilator would improve exercise function after Fontan. Purpose: To determine whether treatment with iloprost, (ILO, a potent, selective, inhaled pulmonary vasodilator) improves exercise function in pts with Fontan.

Methods:
Double-blind, randomized, placebo controlled, crossover trial. All pts performed 2 symptom-limited cardiopulmonary exercise tests (CPX) on different days separated by <1 month. Nebulizer treatment was administered before each test; one contained ILO (5 mcg), the other placebo.

Results:
We recruited 18 Fontan pts aged 12-49 (median 18) yrs. Mild throat/chest discomfort developed in 10/18 pts during ILO administration; all but 1 were able to complete treatment. No symptoms were reported during placebo treatments (p<0.001). Two additional pts did not complete CPX: one was noted to be in recurrent atrial flutter, the other, with developmental issues, could not cooperate adequately for CPX. In the 15 subjects with analyzable CPX data, oxygen pulse (a surrogate for stroke volume) at peak exercise was significantly higher following ILO treatment (11.7±2.7 ml/beat vs. 10.4±2.1 ml/beat following placebo; p<0.001). Peak oxygen consumption (VO
2
) trended higher after ILO compared to placebo (28.7±6.7 vs. 27.5±5.9 ml/kg/min; p=0.18). Nine pts had a peak VO
2
<30 ml/kg/min following placebo; each of these pts had a higher peak VO
2
following ILO (25.5±4.7 vs. 23.7±4.4 ml/kg/min; p<0.002). In contrast, only 3/6 pts with peak VO
2
>30 ml/kg/min on their placebo study had a higher peak VO
2
following ILO (p<0.04).

Conclusion:
ILO therapy improves peak VO
2
in subjects with compromised exercise function after Fontan palliation. The improvement is related to an increase in the oxygen pulse at peak exercise. The therapy appears to be associated with minor side effects. These findings support the concept of pulmonary vasodilator therapy in Fontan pts with limited functional capacity.
Abstract 9453: Dual Probe Hybrid Molecular PET/MR Imaging of Post-infarct Myocardial Inflammation and Healing
Authors: Majmudar Maulik D , Heidt Timo , Keliher Edmund , Truelove Jessica , Sena Brena , Gorbatov Rostic , Iwamoto Yoshiko , Di Carli Marcelo F , Weissleder Ralph , Nahrendorf Matthias
Published: April 2024

Background:
Myocardial infarction elicits a strong inflammatory response, with profound recruitment of innate immune cells. The magnitude of inflammation influences infarct size and severity of post-MI ventricular dysfunction. Inflammatory monocytes and macrophages produce substantial amounts of myeloperoxidase (MPO), which leads to oxidative stress. In addition, plasma transglutaminase factor XIII (FXIII) plays a key role in wound healing, via its contribution to extracellular matrix organization. Thus, we hypothesize that targeted molecular imaging of FXIII and MPO activity using a hybrid PET/ MRI approach will enable simultaneous in vivo assessment of infarct healing and post-infarct inflammation.

Methods and Results:
To assess in vivo FXIII activity, we developed a fluorine-18 labeled affinity peptide (18F-FXIII), with a blood half-life of 13.3 min, using a facile ‘click-chemistry’ approach. FXIII recognizes the PET probe as a substrate and cross-links it to extracellular matrix proteins, leading to local entrapment within the healing infarct. 18F-FXIII and gadolinium-based activatable sensor of MPO activity (MPO-Gd) were injected in C57BL/6 mice on day 4 after permanent coronary ligation. PET/MR imaging was performed and fusion was facilitated using external fiducial markers. 18F-FXIII uptake in the heart was significantly higher in animals with MI as compared to controls, as measured by scintillation counting (percent injected dose per gram tissue 0.29±0.01 vs 0.17± 0.03, p<0.03). On autoradiography, 18F-FXIII uptake correlated well with infarct area on TTC staining. PET/MR imaging allowed for simultaneous in vivo assessment of MPO and FXIII activity (Figure).

Conclusion:
Dual probe hybrid PET/MR imaging with 18F-FXIII and MPO-Gd allows non-invasive assessment of post-infarct myocardial inflammation and infarct healing.
Abstract 9454: Risk of Incident Hypertension in Relation to Long-term Exposure to Ambient Air Pollution in Ontario, Canada
Authors: Chen Hong , Copes Ray , Burnett Richard T , Kwong Jeff , Villeneuve Paul J , Goldberg Mark S , Brook Robert D , Donkelaar Aaron van , Jerrett Michael , Martin Randall V , Brook Jeffrey R
Published: April 2024

Background - Laboratory studies suggest that exposure to fine particulate matter (2.5μm in diameter or less; PM2.5) can trigger a combination of changes in autonomic nervous system activity, systemic inflammation, and blood pressure which may in turn induce the development of hypertension. However, epidemiological evidence relating PM2.5 and hypertension is sparse. We thus conducted a population-based cohort study to determine whether long-term exposure to PM2.5 is associated with incident hypertension. Methods and Results - We assembled a cohort of 46,591 non-hypertensive adults from Ontario, Canada who responded to one of five population-based health surveys between 1996 and 2005 and were followed-up until December 31, 2010. Incident diagnoses of hypertension were ascertained from the Ontario Hypertension Database, a validated registry of persons diagnosed with hypertension in Ontario (sensitivity=73% and specificity=95%). Six-year average concentrations of PM2.5 at the subjects’ residences were derived from satellite observations. We used Cox proportional hazards models, adjusting for various individual and contextual risk factors such as body mass index, smoking, physical activity, and family income. We examined the presence of effect modification for selected comorbidities and sociodemographic characteristics. During the follow-up period from 1996 to 2010, we identified a total of 12,061 incident cases of hypertension. For every 10μg/m3 increase of PM2.5, the adjusted hazard ratio (HR) was 1.16 (95% confidence interval (CI): 1.09-1.24). The strongest evidence for an interaction between PM2.5 and hypertension was for congestive heart failure (CHF): HRs of 2.75 (95% CI: 1.26-5.97) and 1.15 (95% CI: 1.08-1.23) among subjects with and without CHF, respectively (interaction p=0.02). Conclusions - This study suggests that exposure to PM2.5 may be a contributing risk factor to the development of hypertension.
Abstract 9460: Robotic Surgery in Obstructive Sleep Apnea Syndrome to Reduce the Cardiometabolic Risk in Hypertensive Patients
Authors: Lenti Salvatore , Burali Giulia , Felici Mario , Ciabatti Pier Guido
Published: April 2024

Introduction
. It is confirmed the association between OSAS (Obstructive Sleep Apnea Syndrome) and increased cardiometabolic risk in obese hypertensive patients, determined by a multifactorial origin and by the activation of the adrenergic system. In the OSAS the apneas and arousals always end with a hypertensive peak that occurs in the phase of hypoventilation, altering the normal nocturnal Blood Pressure (BP) pattern that it is similar to the daytime pattern.

The aim of the study
. Assess the reduction in BP, sleep apnea and metabolic parameters in hypertensive patients undergoing Robotic Surgery using TORS (Trans Oral Robotic Surgery) with Da Vinci Robot, compared to a control group subjected to CPAP (Continuous Positive Airway Pressure).

Materials and Methods
. We enrolled 32 patients (20 M, 12 F, average age 53 years) hypertensive, undergoing therapy (average drugs taken 3.2) and obese (BMI > 30), with OSAS (diagnosed with polysomnography presenting AHI - Apnea-Hypopnea Index - > 30), with alterations in metabolic parameters (LDL > 156 mg/dL, glycated hemoglobin > 7.0 %), S02 < 85%, with Mean Arterial Pressure (MAP) of 136 mmHg during a 24 h BP monitoring (ABPM) with non-dipper profile, with ECG Heart Rate (HR) increase > 80, with values of NT pro-BNP (Brain Natriuretic Peptide N-terminal) > 500 pg/mL, and underwent TORS with the lingual tonsil resection, tonsillectomy and septoplasty. Also were compared with 30 patients, with similar demographic and clinical characteristics, who underwent CPAP.

Results
. After 6 months we obtain an average reduction of AHI 5, improvement in metabolic parameters (LDL < 130 mg/dL, glycated hemoglobin < 6.0 %), the MAP has been reduced to 106 mmHg (profile dipper), the HR has been reduced to less than 60, and we have also observed a reduction of the NT pro-BNP values to < 300 pg/mL; also there was a reduction in therapy (2.2 drugs taken). While in the group with CPAP we only recorded S02 > 95%, MAP 120 and reduced AHI between 15 and 18.
Conclusions
. The TORS although an invasive surgical technique, but more specific and aesthetically better, has showed a significant reduction of AHI, cardiometabolic parameters and BP compared to the use of CPAP, contributing to greater therapeutic efficacy with reduced need for medications.
Abstract 9478: Malignant Early Repolarisation is Relatively Frequent in Young Athletes
Authors: Di Valentino Marcello , Siragusa Patrick , Moschovitis Giorgio , Gallino Augusto , Menafoglio Andrea
Published: April 2024

Background:
early repolarisation in infero-lateral leads (ER), a common ECG pattern in athletes, has been recently linked with an increased risk of cardiac death. Some phenotypes of ER seems to be more “malignant”: J waves in inferior leads with horizontal/descending ST pattern particularly with J wave amplitude > 2 mm. The aim of this study was to assess the proportion of “malignant” ER in a cohort of young athletes.

Methods:
ECG was analysed as part of a prospective study about the impact of cardiovascular screening with ECG in young (14-35 years) athletes. ER was defined as J point elevation ≥ 1 mm in 2 or more contiguous leads (except V1-V3). Following features were noted: localisation of ER (inferior, lateral or infero-lateral), amplitude of J point, morphology of J wave (notch, slurred or indeterminate), ST segment pattern (ascending, horizontal/descending).

Results:
ECG of 1070 athletes (75 % males, age 19.7 ± 6.3 years) was analysed. An ER pattern was present in 383 athletes (36 %). Localisation of ER was infero-lateral in 40%, lateral in 32 % and inferior in 28%. Maximal amplitude of J point was ≥ 2 mm in 25 % of ER pattern. The morphology of J wave was notch in 55 %, slurred in 26 % and indeterminate in 19 %. The ST segment was ascending in 77 % and horizontal/descending in 23 %. ER with a horizontal/descending ST pattern in inferior leads (“malignant” ER) represented 23 % of total ER and was present in 8 % of athletes, with J wave amplitude > 2 mm in 2 % of athletes (5% of total ER). No athlete with ER suffered from syncope of undetermined origin or had family history of premature sudden death.

Conclusions:
ER in young athletes is generally characterised by a notch J wave in lateral leads with ascending ST pattern. The “malignant” phenotype is however relatively frequent. This should be take into account before drawing premature conclusion about risk stratification in this young healthy population.
Abstract 9496: Multiphasic Triacylglycerol Dynamics in the Intact Heart During Acute In Vivo Overexpression of CD36
Authors: Carley Andrew N , Bi Jian , Wang Xueron , O'Donnell J. Michael , Lewandowski E
Published: April 2024

The cardiac triacylglycerol (TAG) pool is a dynamic buffer for the intracellular availability of long chain fatty acid (LCFA), a critically important source of nuclear receptor ligand and oxidative fuel for the beating heart. In addition, the TAG pool prevents the accumulation of potentially toxic LCFA derivatives. However, specific kinetics of LCFA incorporation into TAG in the intact, beating heart are largely uncharacterized, and the mechanisms linking uptake and storage dynamics have until now remained elusive. This work examines TAG dynamics in the intact rat heart, under normal conditions and in response to acute, gene expression-induced changes in in vivo protein-mediated lipid uptake. Dynamic mode 13C NMR of beating rat hearts elucidated multiple kinetic processes in 13C-palmitate incorporation into TAG: an initial saturable exponential component and a slower linear rate. While previous work indicates the linear component to reflect TAG turnover, we hypothesized the saturable exponential to reflect transport of LCFA across the sarcolemma. Thus, we overexpressed the LCFA transporter, CD36 through cardiac-specific adenoviral infection (adv.CD36) in vivo. Within 72 hours, CD36 expression was increased 40% in intact hearts, accelerating the exponential phase (highlighted in Figure 1) with a 60% reduction in the time constant relative to PBS infused hearts (adv.CD36: 1.29±0.24, PBS: 3.18±0.53 min, n=5, p<0.05). CD36 overexpression also increased TAG turnover rates and the corresponding expression of key a TAG synthase, DGAT1, and lipase, ATGL. The results demonstrate coupling LCFA uptake across the sarcolemma to intracellular TAG dynamics and coordination of these events by reciprocal control of gene expression in the heart. Thus, a model system of reciprocal regulation between altered LCFA uptake, and TAG synthesis / lipolysis is elucidated that buffers potentially reactive free fatty acids while maintaining ligands and high energy fuel capacity.
Abstract 95: Does Real-Time Audiovisual Feedback for Public Access Defibrillation Enhance Device Usability and Outcomes? A Simulated Pilot Study on a Disposable Home-Use Defibrillator
Authors: Di Maio Rebecca , Brody David , McAnlis James , Crawford Lauren , McCanny Paul , McIntyre Allister , Howe Andrew
Published: April 2024

Introduction:
A public access defibrillator (PAD) must be simple to operate, because in many cases the operator is a first-time user with minimal or no training. Effective treatment should be delivered to the patient in a manner which emphasises safe use of the device and minimises the risk of injury to patient and rescuer. We assessed the hypothesis that the addition of audio-visual feedback delivered to PAD users ensures they correctly place the electrodes, quickly and safely deliver a defibrillation shock, and effectively administer CPR.

Methods:
Informed consent was received from 24 participants (58% male) who took part in this prospective randomised study. The participants were split into two groups - BLS trained and untrained, and randomly assigned a training defibrillator (HeartSine PDU 400 or Philips FRx). The participants were videoed so that CPR and resuscitation quality parameters could be retrospectively analysed. Between the trained and untrained group we measured differences in time to first shock, adequacy of pad placement and time to place pads as main outcome parameters, and, compression depth and rate, correct hand positions and adherence to hands- off prompts as secondary outcome parameters.

Results:
All 24 participants delivered a rescue shock. The minimally trained group had the fastest time to first shock (94±23 sec versus 139±53 sec, p=0.017) and the fastest time to place pads (69±19 sec versus 115±52 sec, p=0.012). There was no statistical difference between the two groups in terms of electrode placement, CPR quality, and adherence to hands-off prompts or the device used.

Conclusions:
It can be concluded that audio-visual feedback systems in PADs allow minimally trained and untrained users administer effective defibrillation therapy and CPR to SCA victims. The main difference seen between the two groups is the time to first shock, which may represent the untrained users’ hesitancy to initiate the resuscitation by turning on the PAD.
Abstract 9509: Prognostic Value of Treadmill Stress Echocardiography at Extremes of Exercise Workload: Submaximal, <85% Maximum Predicted Heart Rate and High Exercise Capacity, ≥10 Metabolic Equivalents
Authors: Yao Siu-Sun , Agarwal Vikram , Chaudhry Farooq A
Published: April 2024

Background:
Submaximal stress testing, <85% maximum predicted heart rate (MPHR) may be non diagnostic and high exercise capacity (≥10 metabolic equivalents, METS) is a predictor of favorable prognosis. The purpose of this study was to evaluate the prognostic value of submaximal and high exercise capacity stress echocardiography (EXSE).

Methods:
We evaluated 1781 patients (55 ± 13 years; 59% male) undergoing EXSE divided into 811 with submaximal (<85% MPHR) and 970 with high exercise capacity (≥10 METS). Resting left ventricular ejection fraction and wall motion was assessed. The left ventricle was divided into 16 segments and scored on a 5-point scale of wall motion. Abnormal EXSE was defined as stress-induced ischemia (wall-motion score of ≥1 grade). Follow-up (3.3 ± 1.5 years) for non-fatal myocardial infarction (n = 40) and cardiac death (n = 52) were obtained.

Results:
By univariate analysis, exercise work load (p<0.0001), ejection fraction (p<0.0001) and number of new ischemic wall motion abnormalities (p<0.0001) were significant predictors of cardiac events. Cumulative survival was significantly worse in patients with abnormal vs. normal EXSE in submaximal (4.5%/year vs. 1.4%/year, p<0.0001) and high exercise capacity groups (1.1%/year vs. 0.2%/year, p=0.001) (Graph). Multivariate logistic regression analysis identified number of new ischemic wall motion abnormalities as the best predictor of cardiac events (p<0.05) in both groups.

Conclusions:
Despite normal EXSE, inability to achieve 85% MPHR conferred a higher, intermediate event rate of 3.0%/year. The ability to achieve nine minutes (≥10 METS) on EXSE conferred a benign prognosis (1.0%/year) regardless of EXSE results. In either group (submaximal or high exercise capacity), EXSE results (absence or presence ischemia) were useful in further, effectively risk stratifying patients.
Abstract 9534: Expression of Heme Oxygenase-1 in Cardiac Stem Cells Enhances the Efficacy of Cell Therapy for Attenuating Left Ventricular Dysfunction and Remodeling After Myocardial Infarction
Authors: Li Qianhong , Guo Yiru , Ou Qinghui , Wu Wen-Jian , Zhu Xiaoping , Luo Li , Li Jun , Bolli Roberto
Published: April 2024

Although transplantation of cardiac stem cells (CSCs) improves LV function and structure after myocardial infarction (MI), this salubrious effect is limited by early massive CSC loss due to apoptosis. Heme oxygenase-1 (HO-1) is known to exert potent antiapoptotic and cytoprotective effects. Thus, we hypothesized that expression of HO-1 in CSCs will enhance their survival and reparative ability. To test this hypothesis, lin
-
/c-kit
+
CSCs were isolated and expanded from wild-type (WT), HO-1 transgenic (TG) or knockout (KO) mice. HO-1 protein overexpression in HO-1
TG
CSCs (confirmed by FACS and immunoblotting) was mild (3-fold greater than WT CSCs). Mice underwent a 60-minute coronary occlusion followed by reperfusion; 48 h later, they received intramyocardial injection of vehicle or WT, HO-1
TG
or HO-1
KO
CSCs (10
5
CSCs/heart). Sham mice underwent 1-hour open-chest state with no intervention. At 35 days post-MI, both WT and HO-1
TG
CSC transplantation resulted in alleviation of LV dysfunction and remodeling compared with vehicle group; however, the magnitude of the beneficial effects of HO-1
TG
CSCs was significantly greater than that of WT CSCs. Compared with WT CSCs, transplantation of HO-1
TG
CSCs resulted in a greater improvement in global and regional LV function (assessed by two independent methods - echocardiography and conductance catheter) and a greater increase in viable myocardial tissue in the risk region, suggesting increased formation of new cardiomyocytes (Fig). In contrast, transplantation of HO-1
KO
CSCs failed to produce any LV structural or functional benefits. These results indicate, for the first time, that even a mild increase in HO-1 promotes CSC competence and that expression of HO-1 is a powerful strategy to enhance the cardiac reparative actions of CSCs in limiting LV dysfunction and remodeling post-MI. The data provide a potential therapeutic approach for promoting myocardial regeneration via modification of CSCs with cytoprotective genes.
Abstract 9575: Incidence of Subsequent Acute Coronary Syndrome in Patients with Atrial Fibrillation
Authors: Shroff Gautam R , Heubner Brooke M , Schein Jeff , Crivera Concetta , Herzog Charles A
Published: April 2024

Background
. Cardiovascular comorbidities associated with atrial fibrillation (AF) are also risk factors for acute coronary syndrome (ACS). We sought to determine the incidence of subsequent ACS in Medicare pts with newly diagnosed AF.

Methods
. The 5% Medicare database was used to identify pts (age 65+, no ESRD) with AF in 2006 without a prior diagnosis of ACS or AF. Medicare claims were used to identify patients hospitalized with ACS using ICD-9-CM codes for acute myocardial infarction (410) and unstable angina (411). The cumulative incidence of ACS and death was calculated during 3-year follow up using competing risk analysis and independent predictors of ACS were identified using a Cox proportional hazards model.

Results
. 18,445 Medicare pts were newly diagnosed with AF in 2006. The baseline characteristics of this population were: age 78 ± 7.8 yrs, hypertension (67%), CAD (33%), DM (26%), dyslipidemia (24%), CHF (21%), CVA/TIA (15%). 1392 (8%) patients from this cohort received an ACS diagnosis within 3 years (Figure). The rate of incident ACS was 11% in pts with prior CAD, CHF or DM. The rates of death at 3 years varied by age (49% for age ≥ 85, 26% for ages 75-84, 16% for ages 65-74). Independent risk factors for incident ACS included: female gender (HR 1.38, p==0.003), prior CAD (HR 1.78, p<0.0001), DM (HR 1.48, p <0.0001), CHF (HR 1.41, p <0.0001).

Conclusion
. Pts with a new diagnosis of AF had an 8% incidence of ACS within 3 years of the diagnosis of AF; this risk was higher in the presence of comorbid conditions. These data have important implications in chronically anti-coagulated AF pts, as the subsequent diagnosis of ACS will entail additional antiplatelet therapy and increased hemorrhagic risk. In elderly pts with AF, however, mortality is much more frequent than subsequent ACS.