bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15240: Cholesterol Crystal Embolization: The Incidence as a Cardiac Procedural Complication and the Comparison of the Outcomes Between its Causes
Authors: Misao Ayumi , Kadota Kazushige , Hasegawa Daiji , Habara Seiji , Tada Takeshi , Tanaka Hiroyuki , Fuku Yasushi , Goto Tsuyoshi , Mitsudo Kazuaki
Published: April 2024

Background:
Cholesterol crystal embolization (CCE) is very rare, but has a poor prognosis and no proven therapy. Although CCE occurs from various causes, the incidence and outcomes of CCE remain unclear.

Purpose:
1) to investigate the incidence of CCE as a complication of percutaneous coronary intervention (PCI), percutaneous transluminal angioplasty (PTA), and cardiovascular surgery; and 2) to investigate patient characteristics and outcomes of CCE on the basis of its causes: idiopathic CCE, catheter-related CCE, and cardiovascular surgery-related CCE.

Methods:
We registered 75 patients having CCE in the medical records between May 2004 and April 2014 and compared their patient characteristics and outcomes according to the causes of CCE: idiopathic CCE, 31 patients (41%); catheter-related CCE, 32 (43%); and cardiovascular surgery-related CCE, 12 (16%). CCE was diagnosed by clinical findings (blue toe syndrome or livedo) or laboratory findings (elevated serum creatinine level, eosinophil count, or skin biopsy).

Results:
The incidences of catheter-related CCE were 0.7% in PTA on arteriosclerotic obliterans and 0.17% in PCI. The incidence of CCE after PCI was significantly higher in patients treated with femoral approach than in those treated with nonfemoral approach (0.32% vs. 0.01%, p<0.001). The incidences of cardiovascular surgery-related CCE were relatively high in endovascular aortic repair (1.3%) and in abdominal aortic replacement (0.6%).

In the comparison of patient characteristics between idiopathic CCE, catheter-related CCE, and cardiovascular surgery-related CCE, there were significant differences in age and aortic aneurysm. Of the 75 patients, 24 (32%) died, 10 (13%) initiated dialysis, and 7 (9%) underwent leg or toe amputation. There was no significant difference in the outcomes of CCE depending on its causes.

Conclusion:
The incidences of CCE were significantly high in transfemoral procedures and in surgery for abdominal aortic aneurysm. Between the causes of CCE, there were significant differences in patient characteristics, but no significant differences in the outcomes.
Abstract 15243: Does Renal Haemodynamics Relate With Cardiac and Aortic Haemodynamics in the Early Stages of Essential Hypertension?
Authors: Kintis K. , Tsioufis Costas , Koutra E. , Nikolopoulou L. , Kasiakogias A. , Andrikou I. , Ioannidis I. , Filis K. , Patsilinakos S. , Tousoulis D.
Published: April 2024

Introduction:
The relationship of renal haemodynamics with cardiac and aortic hameodynamics is still unclear.

Hypothesis:
We evaluated the relationship of increased renal resistive index (RRI) with Augmentation index (AIx) and cardiac haemodynamics by means of mitral annular early diastolic velocity (E/Ea) in untreated patients with essential hypertension.

Methods:
76 newly diagnosed untreated non diabetic patients with stage I-II essential hypertension [35 males, aged 50 years, office blood pressure (BP) = 143/ 91 mm Hg], underwent ABPM, complete echocardiographic study for determination of E/Ea and blood sampling for assessment of metabolic profile. Moreover, data on renal resistive index (RRI), obtained by Doppler ultrasound sampling of the intrarenal arteries, as well as augmentation index (AIx), were retrospectively analyzed.

Results:
Based on the mean value of RRI (0.60), hypertensives were classified into those with high and low RRI. Hypertensives with high RRI values compared to those with low values were older (55.6±9.8 vs 44.4±11.6 years, p < 0.001), had lower 24-hour diastolic BP (77.5±7.7 vs 84.3±6.7 mmHg, p < 0.001), lower 24-hour HR (71.2±10.3 vs 76.2±9.2 bpm, p < 0.05), higher levels of AIx (27.2±8.2 vs 17.8±14.8 %, p < 0.01), and higher values of E/Ea (lateral) (7.7±1.8 vs 6.2±2.3, p < 0.05). In the total population, RRI was negatively related to 24-hour diastolic BP (r = -0.523, p < 0.001) and 24-hour HR (r = -0.281, p < 0.05), while it was positively associated with CRP (r = 0.335, p < 0.05), TChol (r = 0.296, p < 0.01), age (r = 0.443, r < 0.001), AIx (r = 0.413, p = 0.001) and E/Ea(lateral) (r = 0.465, p < 0.05). Multiple regression analysis revealed that 24-hour diastolic BP and E/Ea (lateral) were independent associated with RRI (R2 = 0.434, p < 0.05).

Conclusions:
Increased vascular resistance of intrarenal arteries is associated with impaired aortic and cardiac haemodynamics, as reflected by increased AIx and E/Ea (lateral) values. RRI may be considered a useful surrogate of haemodynamics in essential hypertension.
Abstract 15298: Effects of Transendocardial CD34+ Cell Transplantation on Diastolic Parameters in Patients With Non-ischemic Dilated Cardiomyopathy
Authors: Bervar Mojca , Kozelj Mirta , Poglajen Gregor , Sever Matjaz , Cukjati Marko , Cernelc Peter , Haddad Francois , Wu Joseph C , Vrtovec Bojan
Published: April 2024

Introduction:
The underlying mechanisms of CD34+ cell therapy in patients with non-ischemic dilated cardiomyopathy (DCM) are poorly defined.

Hypothesis:
In a substudy of a protocol investigating the clinical effects of transendocardial CD34+ cell transplantation in DCM we sought to evaluate the effects of this therapy on diastolic parameters.

Methods:
From May 2013 until January 2014 we enrolled 38 DCM patients with NYHA class III and LVEF <40%. All patients underwent transendocardial CD34+ cell transplantation. Peripheral blood CD34+ cells were mobilized by G-CSF, collected via apheresis, and injected transendocardially in the areas of electomechanical missmatch. Patients were followed for 1 year after the procedure.

Results:
At baseline, diastolic parametes were impaired (E/Em≥15) in 18 patients (Group A), and normal (E/Em<15) in 20 patients (Group B). The two groups did not differ in age (54±9 years vs. 52±10 years; P=0.62), gender (male: 85% vs. 78%; P=0.57), or LVEF (31±7 % vs. 34±6 %; P=0.37). When compared to Group B patients in Group A had more segments with myocardial scar (4.9±2.7 vs. 2.7±2.9; P=0.03). and myocardial hibernation (2.2±1.6 vs. 0.9±1.1; P=0.02) on electroanatomical mapping. The number of injected CD34+ cells was 92.6±45.8 million in Group A, and 139.2±85.3 million in Group B (P=0.08). During follow-up there was an improvement in diastolic parameters in Group A (E/Em: from 24.3±12.1 to 16.3±8.0; P=0.005), but not in Group B (E/Em: from 10.2±3.7 to 13.2±9.1; P=0.19). Accordingly, in Group A, we found an increase in 6-minute walk distance (from 463±83 m to 546±91 m; P=0.03), and a decrease in NT-proBNP (from 2140±1743 pg/mL to 863±836 pg/mL; P=0.02).

Conclusions:
In non-ischemic DCM, diastolic parametes appear to correlate with areas of myocardial scar and hibernation on electroanatomical mapping. Transendocardial CD34+ cell transplantation may improve diastolic parameters in this patient cohort.
Abstract 15350: Dietary Omega-3 Fatty Acids and Fiber Intake Increase Adiponectin Levels in African American Adults With Metabolic Syndrome
Authors: Ferranti Erin P , Butts Brittany , Reilly Carolyn M , Dunbar Sandra B
Published: April 2024

Introduction and Purpose:
Adiponectin is a key peptide involved in the relationship between adiposity, insulin resistance and inflammation. Lower plasma levels are associated with metabolic syndrome (MetS), type 2 diabetes mellitus, and coronary artery disease. African Americans (AA) have lower levels of adiponectin compared to other racial/ethnic groups. While clinical trials have examined the effects of dietary intake of omega-3 fatty acids, fiber, and other nutrients on adiponectin levels and metabolic risk, few studies have examined these relationships in AA adults. The purpose of this study is to examine the relationship between dietary factors and adiponectin in AA adults with MetS.

Methods:
This analysis is of baseline data from a larger, longitudinal lifestyle intervention study in AA adults with metabolic syndrome. Dietary intake was assessed with the 2005 Block Food Frequency Questionnaire. Plasma adiponectin was measured by ELISA. Analysis included descriptive statistics, correlations and multiple regression.

Results:
Seventy-four participants, 50.5±9.1 years of age, 77% female, were included in this analysis. Most participants (N=62, 85%) were obese, with mean BMI 35.6±6.3 and mean waist-hip ratio (W:H) 0.95±.05 for males and 0.88±.08 for females. Mean omega-3 intake was .77±0.5g and fiber intake was 15.47±7.9g. Adiponectin was higher in females than males (7.7±4.0 vs 5.4±3.3, t=-2.8, p=.007) and negatively associated with W:H (r=-.20, p=.03). Adiponectin had a positive linear relationship with omega-3 (R2=.235, p=.003) and fiber (R2=.201, p=.015) intake, controlling for gender and W:H. These relationships are consistent with studies in other ethnic groups.

Conclusion:
Higher adiponectin levels are protective with metabolic risk factors, particularly central adiposity. Increased consumption of omega-3 fatty acids and fiber is associated with higher levels of adiponectin and may confer risk protection in AA adults with MetS. Culturally tailored strategies aimed at improved dietary quality, particularly focused on increasing dietary intake of omega-3 fatty acids and fiber are warranted.
Abstract 15426: Inflammasome-induced Signalling Mechanisms via Microparticles
Authors: Pfeifer Philipp , Felix Jansen , Zimmer Sebastian , Schild Katharina , Latz Eike , Franklin Bernardo , Nickenig Georg , Werner Nikos
Published: April 2024

Introduction:
The inflammasome, a multi-protein signaling platform, has been shown to be an important mediator in the development of atherogenesis. Microparticles (MPs) are small membrane vesicles, which are released from apoptotic cells. Whether inflammasome activation leads to the release of MPs by vascular cells is unknown.

Hypothesis:
Inflammasome-activation in vascular cells leads to microparticle release. These microparticles contain components of the inflammasome and exert functional effects on other vascular cells.

Methods:
EMP (endothelial microparticles) and MMP (monocytic microparticles) were quantified by flow cytometry using TruCount tubes. Inflammasome-activation was investigated by IL-1β ELISA and immunoblotting. The latter was also used to determine EMP content. Viability Assay was performed to test cell-viability and Scratch assay to examine effects of EMP on migration and proliferation of vascular cells.

Results:
Human coronary artery endothelial cells (HCAEC) and monocytes were primed with LPS and subsequently stimulated with either ATP or Nigericin, two established inflammasome activators. MP release was quantified by flow cytometry using TruCount tubes. Stimulation of HCAEC and monocytes with both Nigericin and ATP resulted in a time-dependent release of MPs.

Inflammasome-activation in HCAEC was confirmed by the release of IL-1β into the cell supernatant and immunoblotting against Caspase-1. Immunoblotting also showed that inflammasom-activated HCAEC and the associated EMP contain pro-Caspase-1, active Caspase-1 and NALP-3.

Inoculation of HCAEC with EMP, derived from HCAEC stimulated with Nigericin, lead to a rapid and significant cell death and reduced cell migration/ proliferation shown by Viability Assay and Scratch Assay, respectively.

Conclusions:
We show for the first time that Nigericin and ATP, two established inflammasome activators, lead to inflammasome activation and release of microparticles by vascular cells. Furthermore, we could demonstrate that these microparticles contain pro-Caspase-1, mature-Caspase-1 and NALP-3 and that they cause cell death accompanied with reduced cell migration and proliferation.
Abstract 15464: Clinical Features and Impact on Clinical Outcome of Cerebral Microbleeds in Patients With Active Infective Endocarditis
Authors: Murai Ryosuke , Kaji Shuichiro , Sasaki Yasuhiro , Ota Mitsuhiko , Kim Kitae , Kitai Takeshi , Yamane Takafumi , Kobori Atsushi , Ehara Natsuhiko , Kinoshita Makoto , Furukawa Yutaka
Published: April 2024

Background:
Cerebrovascular complications are frequently observed in patients with infective endocarditis (IE). Cerebral microbleeds (CMB) are an increasingly recognized neuroimaging finding by newer MRI methodologies in patients with active IE. However, the clinical features of CMB and their impact on clinical outcomes still remain unclear. The purpose of this study was to assess the clinical features of CMB and their association with clinical outcomes.

Methods:
From January 2009 to June 2014, 117 patients with active IE diagnosed by modified Duke’s criteria were retrospectively reviewed. Among them, brain MRI was performed in 90 patients, and 68 patients whose MRI data were available for the assessment of CMB were finally enrolled in the current analysis. CMB were defined as T2* or susceptibility weighted imaging (SWI) hypointense lesions with a diameter <10mm.

Results:
Of the 68 patients, 34 showed CMB (CMB group) and 34 did not (non-CMB group). The incidences of concomitant cerebral infarction (CMB vs non-CMB: 56% vs 47%, p=0.63) and cerebral hemorrhage (16% vs 21%, p=0.72) were comparable between the groups. There were also no significant difference in the incidence of symptomatic cerebral complications (24% vs 35%, p=0.43). It is noteworthy that significantly high prevalence of Staphylococcal IE was observed in CMB group (38% vs 12%, p=0.014). Diseased valves were not differ between the groups, but more patients with prosthetic valve endocarditis (PVE) were included in CMB group (35% vs 3%, p<0.01). Surgical intervention was performed in 24 (71%) patients in CMB group and 23 (68%) in non-CMB. There were no significant difference in the incidences of de novo stroke following cardiac surgery (17% vs 13%, p=1.00). In-hospital mortality rate and estimated 1-year major adverse event-free rate between two groups were not significantly different (8.8% vs 8.8%, p=1.00; 85% vs 88%, p=0.40, respectively).

Conclusions:
CMB in IE patients were associated with high prevalence of Staphylococcal IE and PVE. However, CMB were not a predictor of poorer in-hospital and mid-term clinical outcomes.
Abstract 15498: Partial Band Mitral Annuloplasty Can Preserve Mitral-aortic Valve Dynamic Coupling After Mitral Valve Repair in Comparison With Complete Ring Plasty
Authors: Wakana Noriyuki , Yamano Tetsuhiro , Watanabe Hiroyuki , Yamano Michiyo , Nakanishi Naohiko , Ogata Takehiro , Nakamura Takeshi , Shiraishi Hirokazu , Ueyama Tomomi , Matoba Satoaki , Yamada Hiroyuki , Doi Kiyoshi , Matsumuro Akiyoshi , Shirayama Takeshi , Yaku Hitoshi
Published: April 2024

Introduction:
The aortic and mitral valves (MV) demonstrate synchronous behavior to facilitate both left ventricular (LV) filling and emptying. Although partial band (PB) mitral annuloplasty is often performed to maintain anterior annulus flexibility, actual advantages remain undefined. The object of this study is to identify the effects of PB annuloplasty compared with complete ring (CR).

Methods:
We retrospectively evaluated 24 patients who underwent MV repair for degenerative mitral regurgitation. A PB (CG Future band, Medtronic Inc) was used in 13 patients and a CR (Carpentier-Edwards Physio or Physio II ring, Edwards Lifesciences) in 11. Three-dimensional transesophageal echocardiography was performed and 4D-MV Assessment, 2.0 (TomTec Imaging Systems) was used for semiautomatic tracking of mitral annulus (MA). Aortic annulus (AoA) was manually traced frame by frame in transverse plane perpendicular to LV outflow tract at the level of hinge points of sinuses, which was reconstructed from three-dimensional datasets.

Results:
MA surface and AoA projected areas changed reciprocally throughout cardiac cycle (Fig a and b). The PB orifice area measured in vitro was smaller than CR (4.8±0.9 vs 5.8±1.2 cm2, P<0.05). There was no difference in patients’ body surface area (1.57±0.21 vs 1.67±0.20 m2). However, the MA area in PB constantly tended to be larger than in CR (maximum area: 8.1±2.0 vs 6.7±1.5 cm2, P=0.09, Fig a). In PB, MA surface area change was greater (10.1±6.0% vs 5.9±2.9%, P<0.05: Fig c); consequently, AoA projected area change was much larger than in CR (39.2±11.0% vs 18.4±4.2%, P<0.01: Fig d). Immediately postoperative residual regurgitation was none or of mild degree in all patients, and Doppler transmitral mean pressure gradient tended to be smaller in PB than in CR (2.0±0.4 vs 2.3±0.9 mmHg, P=0.32).

Conclusions:
PB mitral annuloplasty could preserve mitral-aortic dynamic coupling, which must provide important consideration at the time of MV repair.
Abstract 15512: Sodium Intake and All-Ccuse Mortality Over 20 Years of Follow-up
Authors: Cook Nancy R , Appel Lawrence J , Whelton Paul K
Published: April 2024

Introduction:
While several studies suggest beneficial effects of lower sodium on cardiovascular disease, the relationship with total mortality remains controversial. Some have reported a J-shaped curve, but this may be due to poor quality exposures or confounding bias.

Methods:
Two trials [Phase 1 (1987-90) and Phase 2 (1990-5) of the Trials of Hypertension Prevention] implemented sodium reduction interventions, over 18 months in Phase I and 36 months in Phase II. Multiple 24-hour urine specimens were collected from pre-hypertensive adults aged 30-54. In extended post-trial follow-up, deaths were ascertained through December 31, 2013 using the National Death Index. We assessed the relation of the randomized sodium interventions, as well as average sodium excretion among those not assigned to an active sodium intervention, with all-cause mortality through 23-26 years.

Results and Conclusions:
Among 744 Phase I and 2382 Phase II participants randomized to sodium reduction or control, 251 deaths occurred, with a nonsignificant 15% lower risk among those in the active intervention (RR=0.85, 95% CI=0.66-1.09, p=0.19). Among 3021 usual care participants, 273 deaths occurred. There was a direct but nonsignificant association of average sodium excretion with mortality, with hazard ratios (HRs) of 0.73, 0.97, 1.00 (reference), and 1.03 (p-trend = 0.38) over <2300, 2300-<3600, 3600-<4800, and >=4800 mg/d after adjustment for trial variables, with an HR=1.10 per 1000 mg/day (95% CI = 0.98-1.24, p=0.09). There was no evidence of a J-shape or other nonlinear relation. The sodium/potassium ratio had an HR=1.11 per unit (95% CI = 0.99-1.25, p=0.07). While the results did not reach statistical significance, they are consistent with a benefit of sodium reduction on total mortality over a period of over 20 years. This study, with carefully characterized measures of sodium intake, found no inverse relation with total mortality, even at the lowest levels of sodium intake.
Abstract 15524: Can a Home-based Cardiac Rehabilitation Program Improve the Physical Function Quality of Life in Children With Fontan Circulation?
Authors: Jacobsen Roni M , Danduran Michael , Mussatto Kathleen , Neubauer Jennifer , Ginde Salil
Published: April 2024

Introduction:
Patients after Fontan operation for complex congenital heart disease (CHD) have reduced exercise capacity and health-related quality of life (HRQOL). Studies suggest hospital-based cardiac rehabilitation programs can improve exercise capacity and HRQOL in patients with CHD; however, these programs have variable adherence rates. The impact of a
home-based
cardiac rehabilitation program in Fontan survivors is unclear. This pilot study evaluated the safety, feasibility, and benefits of an innovative home-based physical activity program on HRQOL in Fontan patients.

Methods:
A total of 14 children, 8-12 yr, with Fontan circulation enrolled in a 12-week moderate/high intensity home-based cardiac physical activity program, which included a home exercise routine and 3 formal in-person assessments at 0, 6, and 12 weeks. Subjects and parents completed validated questionnaires to assess HRQOL. The Shuttle Test Run was used to measure exercise capacity. A Fitbit® Flex Activity Monitor was used to assess adherence to the home activity program.

Results:
Of the 14 subjects, 57% were male and 36% had a dominant left ventricle. Overall, 93% completed the program. There were no adverse events. Parents reported improvement in their child’s overall HRQOL (p<0.01), physical function (p<0.01), school function (p=0.01), and psychosocial function (p<0.01). Exercise capacity, measured by Shuttle Run time, improved progressively from baseline to the 6 and 12 week follow up sessions (Figure). Monthly Fitbit® data suggested good adherence to the program.

Conclusion:
This 12-week home-based cardiac physical activity program is safe and feasible in Fontan patients. Parent proxy-reported HRQOL and objective measures of exercise capacity significantly improved. A 6 month follow up session is scheduled to assess sustainability. A larger study is anticipated to determine applicability and reproducibility of these findings in other age groups and forms of complex CHD.
Abstract 15563: Prognostic Impact of Postprocedual TIMI Flow Grade in STEMI Patients With Cardiogenic Shock Undergoing Primary Percutaneous Coronary Intervention - Analysis From JCS Shock Registry
Authors: Matoba Tetsuya , Sakamoto Kazuo , Mohri Masahiro , Tanaka Nobuhiro , Hokama Yohei , Fukutomi Motoki , Hashiba Katsutaka , Fukuhara Rei , Ueki Yasushi , Suwa Satoru , Matsuura Hirohide , Tachibana Eizo , Yonemoto Naohiro , Nagao Ken
Published: April 2024

Background:
ST-segment elevation myocardial infarction (STEMI) complicated with cardiogenic shock, Killip class 4, is a severe condition with high mortality, for which primary percutaneous coronary intervention (PPCI) is recommended. Cardiogenic shock is a predictor for slow flow/no reflow (TIMI ≤2) during PPCI.

Methods and Results:
The Japanese Circulation Society Cardiovascular Shock registry (JCS Shock registry) was a prospective, observational, multi-center, cohort study. Between May, 2012 and June, 2014, a total of 980 patients with cardiovascular shock were enrolled from 82 centers in Japan. We assessed the prognostic impact of postprocedual TIMI flow grade in 341 patients who underwent primary PCI (PPCI) among 408 STEMI patients. Ninety percent of PPCI were performed within 120 min of arrival, in which thrombus aspiration (TA), stenting, and distal protection (DP) were applied in 228 (67%), 303 (89%), and 29 (9%) patients, respectively. Postprocedual TIMI grade 3 flow was achieved in 283 (83%) patients, whereas TIMI ≤2 in 58 (17%) patients. Thirty-day mortality in subgroups with TIMI 3, TIMI ≤2, and No PPCI (n=66) was 24.0%, 48.3% and 48.5%, respectively (P<0.01 by Chi-square, Fig. A), which suggest the importance of TIMI 3 achievement in PPCI. We compared the rate of postprocedual TIMI 3 in different PCI strategies; (1) TA and stenting without DP (TIMI 3 achievement 84%, n=179), (2) stenting without TA or DP (83%, n=96), (3) TA and stenting with DP (93%, n=27), (4) TA alone (71%, n=21), and (5) None of 3 devices (67%, n=16), suggesting the therapeutic effects of the devices (Fig. B).

Conclusions:
In the JCS Shock registry that observed contemporary emergency cardiovascular care in Japan, 30-day mortality of STEMI complicated with cardiogenic shock was 24% in patients underwent PPCI and resulted in TIMI grade 3 flow in the culprit arteries. The use of TA, stent, and DP in PPCI are associated with the better chances of postprocedual TIMI grade 3 flow.
Abstract 15619: Childhood Physical Fitness Phenotypes and Adult Carotid Arterial Stiffness
Authors: Lankaputhra Malanka , Magnussen Costan G , Dwyer Terence , Venn Alison , Huynh Quan L
Published: April 2024

Background:
Large artery stiffness is associated with fitness phenotypes in adulthood, but the association of childhood physical fitness with adult arterial stiffness is unknown.

Aim:
To determine the longitudinal association of childhood physical fitness phenotypes with adult carotid artery stiffness.

Methods:
Data were from 2,008 participants in the Childhood Determinants of Adult Health Study (52% female) with baseline measurements collected in 1985 when aged 7-15 years and follow-up measurements collected 20 years later. Fitness measures included muscular strength (isometric handgrip, shoulder, and leg strength), power (standing long jump), endurance (number of push-ups in 30 seconds), cardiorespiratory fitness (physical work capacity at heart rate of 170 bpm [PWC170] and time to complete a 1.6km run), and flexibility (sit and reach distance). All predictors were expressed as age- and sex-specific z-scores. Arterial stiffness was measured as carotid distensibility (CD) by ultrasound.

Results:
In univariable analysis, no association was found between childhood muscular strength (β=-0.029), power (β=-0.013), endurance (β=0.00051), PWC170 (β=0.00045), 1.6km run: (β=-0.0077), and adult CD (all p>0.30). However, an association was present for flexibility in childhood and adult CD (β=-0.038, p=0.028). Following adjustment for relevant adult measures, age and sex, no childhood physical fitness measures were associated with adult CD (muscular strength: β=-0.044; power: β=0.0077, endurance: β=0.017; PWC170: β=-0.0010; 1.6km run: β=0.0058, flexibility: β=-0.035 all p>0.20).

Conclusion:
Measures of physical fitness in childhood were weakly associated with adult arterial stiffness. Given the reported relationship of adult fitness phenotypes with arterial stiffness, our data suggest current fitness or activities associated with current fitness might play a greater role in determining adult arterial stiffness.
Abstract 15635: Consumption of Aspirin and Naproxen by Platelet Donors and the Quality of Platelet Transfusion
Authors: Li Xuanwen , Fries Susanne , Sachais Bruce S , Cuker Adam , Blair Ian A , Grosser Tilo
Published: April 2024

Over-the-counter pain killers are amongst the most frequently consumed drugs world-wide. Individuals who self-report ingesting aspirin or aspirin containing drugs within the preceding 48-72 hours - depending on regional practice - are excluded from platelet donation, given the assumed platelet functional inhibition due to irreversible acetylation of platelet cyclooxygenase-1 (COX-1) by aspirin and the consequent suppression of thromboxane formation. Other nonsteroidal anti-inflammatory drugs, which bind COX-1 tightly enough to cause long acting platelet inhibition, such as naproxen, may also impact the quality of platelet preparations for transfusion but are not typically exclusionary. The prevalence of functionally relevant exposure of platelet donors to aspirin and naproxen is unknown.

We used sensitive and specific mass spectrometry methods to quantitate the acetylation of platelet COX-1 by aspirin and platelet protein binding of naproxen in platelet transfusion units as indices of donor exposure to these drugs. Platelet thromboxane formation was assessed as a functional parameter. We screened single-donor apheresis platelet units transfused at the Hospital of the University of Pennsylvania.

Over 30 % (71 out of 235) of the analyzed platelet units showed evidence of aspirin exposure ranging from residual COX-1 acetylation after an appropriate washout period to complete acetylation suggestive of recent aspirin exposure. Approximately 7% (16 out of 235) of the platelet units showed complete COX-1 acetylation and inhibition of thromboxane formation. More than 15% (22 out of 143) of analyzed platelet units showed high naproxen concentrations that were associated with depression of thromboxane formation.

The prevalence of aspirin and naproxen consumption by platelet donors is as high as would be expected in the general population and results in transfusion of inhibited platelets with suppressed thromboxane formation.
Abstract 15702: Role of the Drp-1 Receptors Mid49 and Mid51 in Regulating Fission and Cell Proliferation in Pulmonary Arterial Hypertension
Authors: Dasgupta Asish , Chen Kuang-Hueih , Archer Stephen L
Published: April 2024

Introduction:
Pulmonary arterial hypertension (PAH) is a lethal syndrome characterized by pulmonary vascular obstruction that is partially due to hyperproliferation of apoptosis-resistant pulmonary arterial smooth muscle cells (PASMCs). This “neoplastic phenotype” of PAH PASMCs is due, in part, to excessive mitochondrial fission caused by activation of dynamin related protein-1 (Drp-1). A pool of Drp-1 exists in the cytosol. Upon activation it is recruited to the mitochondrial outer membrane by Drp-1 receptor proteins, such as MiD49 and MiD51. The biological functions of these newly discovered Drp-1 receptors in diseases, including PAH, is poorly understood. We hypothesize that in PAH increased expression of MiD49 and MiD51 contribute to increased mitochondrial fission and excessive cell proliferation.

Methods:
Immunoblots quantified MiD49 and MiD51 expression in human control (n=3) and PAH PASMCs (n=6). The effects of silencing expression of MiD49 and MiD51, using small interfering RNA (siRNA), on cell proliferation, cell cycle progression, and rates of apoptosis were assessed using flow cytometry, and a cell death ELISA assay, respectively. Mitochondrial network structure was assessed using confocal imaging of cells stained with tetramethylrhodamine (TMRM).

Results:
MiD49 and MiD51 expression was increased in human PAH PASMCs vs control PASMCs (P<0.05). There was marked inter-individual variation in expression profile with some patients expressing excess MiD49 and others excess MiD51. PAH PASMCs had fragmented mitochondrial networks and both siMiD49 and siMiD51 increased mitochondrial fusion. Either siMiD49 or siMiD51 completely blocked the proliferation of PAH PASMCs by arresting the cells in the G1/G0 phase. In contrast, only siMiD51 induced apoptosis in PAH PASMCs.

Conclusion:
MiD49 and MiD51 are critically involved in mitochondrial fission and cell proliferation in human PAH PASMCs. Inhibition of MiD49 or MiD51 enhances mitochondrial fusion and reduces cell proliferation, while silencing MiD51 also induces apoptosis. These newly discovered Drp-1 binding partners are promising therapeutic targets in PAH.
Abstract 15829: Hybrid Coronary Revascularization versus Multivessel Pci-Stenting: A Propensity Match Analysis
Authors: Repossini Alberto , Tespili Maurizio , Di Bacco Lorenzo , Saino Antonio , Giroletti Laura , Muneretto Claudio
Published: April 2024

Introduction:
Despite current guidelines and the proven LIMA-LAD superiority, PCI-stenting is still largely performed in patients with multi-vessel coronary disease (MVD).

Hypothesis:
We investigated the role of hybrid revascularization (HCR) meaning MIDCAB combined with PCI as a planned strategy and compared it with PCI alone in patients with multi-vessel coronary disease involving proximal LAD.

Methods:
We retrospectively analyzed 605 patients with MVD: 179 hybrid and 426 multi-vessel PCI revascularizations. All patients have been discussed within the heart team, based on pre-operative risk (Logistic EuroSCORE II) and on coronary lesions complexity (SYNTAX score). A propensity score matching has been performed and 127 patients from each series selected. Early results were evaluated, and survival analysis for all-causes mortality, cardiac death and MACCE were performed.

Results:
One-hundred forty-two patients (142/254) had two-vessel disease and 78/254 (41 HCR and 37 PCI patients) had left main involvement. 28 LAD total occlusion in HCR and 18 in PCI groups. 20 PCI patients had recent STEMI and 25 HCR patients. Mean SYNTAX score was 27.5±3.5 and 27±4.0 in HCR and PCI (p=0.8) respectively. No hospital mortality was reported. Overall survival rate at 60 months was (HCR 95% CI: 84.8%, 80.6-91% vs PCI 78.7%, 72.1-85.3%, p=0.23). Freedom from cardiac death survival rate at 60 months was (HCR 95% CI: 91.4%, 85.8-97% vs PCI 84.5%, 78.1-90.9%, p=0.33). Freedom from MACCE survival rate at 60 months was better in HCR group than PCI (95% CI: 74.5%, 66.8-82.4% vs 54.4%, 46.6-62.2%, p=0.015). The reduced target vessel revascularization rate in HCR group was due to LAD repeated revascularization in PCI group.

Conclusions:
Hybrid Coronary revascularization is a safe and effective strategy to achieve a complete revascularization in patients with multi-vessel disease. HCR, reducing SYNTAX score when due to LAD lesions and the number of stents used to complete revascularization, improved results of PCI-stenting in patients with MVD providing a significantly better freedom from MACCE at mid-term.
Abstract 11187: Doxorubicin Provokes Maladaptive Autophagy and Necrotic Cell Death of Cardiac Myocytes by Disrupting Mitochondrial Respiration Chain Complex IV
Authors: Dhingra Rimpy , Gang Hongying , Margulets Victoria , Kirshenbaum Lorrie A.
Published: April 2024

Doxorubicin is known for its cardiotoxic effects and inducing cardiac failure, however, the underlying mechanisms remain cryptic. Earlier we established the inducible - death protein, Bcl-2-like Nineteen- Kilodalton- Interacting - Protein 3 (Bnip3) to be crucial for disrupting mitochondrial function and inducing cell death of cardiac myocytes. Whether Bnip3 underlies cardiotoxic effects of doxorubicin toxicity is unknown. Herein we demonstrate a novel signaling pathway that functionally links activation and preferential mitochondrial targeting of Bnip3 to the cardiotoxic properties of doxorubicin. Perturbations to mitochondria were observed in cardiac myocytes treated with doxorubicin. Impaired mitochondrial function was accompanied by an accumulated increase in autophagosomes and necrosis demonstrated by increase release of LDH, cTnT and loss of nuclear High Mobility Group Protein 1 (HMGB-1) immunoreactivity. Notably, mitochondrial associated Bnip3 in cells treated with doxorubicin formed strong protein interactions with Cytochrome c oxidase subunit1 (COX1) of respiratory chain. This displaced uncoupling protein 3 (UCP3) from COX1 resulting in increased ROS production, decline in maximal and reserved respiration capacity and cell viability. Interestingly, inhibition of autophagy with 3-methyl adenine (3-MA), or Atg7 knock-down suppressed doxorubicin induced necrotic cell death. Importantly genetic inhibition of Bnip3 preserved UCP3-COX complexes, mitochondrial respiratory integrity and abrogated doxorubicin induced necrotic cell death. Moreover, Bnip3-/- mice were resistant to doxorubicin cardiotoxicity displaying normal mitochondrial morphology, cardiac function and survival rates comparable to wild type vehicle treated litter mates. In this report, we demonstrate that doxorubicin provokes maladaptive autophagy resulting in necrotic cell death of ventricular myocytes by a mechanism that involves mitochondria dysfunction induced by the Bcl-2 death protein Bnip3.
Abstract 11202: Life’s Simple 7 and Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis
Authors: Ogunmoroti Oluseye , Salami Joseph A , Michos Erin D , Spatz Erica S , Allen Norrina , Aronis Konstantinos , Blankstein Ron , Rana Jamal S , Virani Salim S , Veledar Emir , Blumenthal Roger S , Szklo Moyses , Blaha Michael J , Nasir Khurram
Published: April 2024

Introduction:
Atrial fibrillation (AF) causes substantial morbidity and mortality. The Life’s Simple 7 (LS7) metrics serve as a marker of “ideal cardiovascular health” and provide a framework for decreasing the overall burden of cardiovascular diseases. We examined the association between the LS7 metrics and incident AF in MESA, a multicenter prospective cohort study.

Methods:
The study population comprised 6,814 men and women, free of established cardiovascular disease at baseline. “Ideal cardiovascular health” was measured from the components of the LS7 metrics (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol and blood glucose). The metrics were categorized into: ideal (assigned 2 points); intermediate (1 point) and poor (0 point). Scores for each participant, were summed for a maximum score of 14. A score of 0-8 was inadequate; 9-10, average and 11-14, optimal. Cox proportional hazard ratios and incidence rates per 1000 person years were calculated from ICD-9 diagnosis of AF. Hazard ratios were adjusted for age, sex, education, income and health insurance.

Results:
After excluding participants with incomplete data, the final study population was 6,506 (53% women, mean age 62 ±10 years). During a median follow-up of 11.2 years, 355 participants (5.5%) developed AF. Overall, optimal and average scores were associated with a lower hazard for AF compared with inadequate scores [0.59 (0.43-0.81) and 0.92 (0.76-1.13) respectively]. A similar trend was mostly observed when the results were stratified by race/ethnicity (Table).

Conclusion:
Favorable LS7 status is associated with a lower risk of AF across all race/ethnic groups. These findings suggest that promoting ideal cardiovascular health may reduce the incidence of AF including its complications and healthcare expenditure.
Abstract 11225: Trends in Atrial Fibrillation Hospitalizations From 1996 to 2010 Using Data From National Hospital Discharge Survey
Authors: Nisar Muhammad U , Sharbaugh Michael S , Thoma Floyd W , Munir Muhammad B , Kamran Amir S , Althouse Andrew D , Saba Samir
Published: April 2024

Aims:
Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Patients presenting with AF are often admitted to the hospital for rhythm or rate control, symptom management, and/or anticoagulation. We investigated temporal trends in AF hospitalizations in the United States from 1996 to 2010.

Methods:
Data were obtained from the National Hospital Discharge Survey (NHDS), a national probability sample survey of discharges conducted annually by the National Center for Health Statistics. Because of the survey design, sampling weights are applied to the raw NHDS data to produce national estimates. Hospitalizations with a primary diagnosis of AF were identified using ICD-9 code. Weighted least squares regression was used to test for linear trends in the number of AF admissions, length of stay, and inpatient mortality.

Results:
AF admissions increased from approximately 286,000 in 1996 to about 410,000 in 2010 with a significant linear trend (β=9460 additional admissions per year, p<0.001). Overall, mean length of stay for AF admissions was 3.75 days, and this remained relatively stable over time (β=0.002 days, p=0.884; see Figure). Inpatient mortality was 0.96% and also remained stable over time (β=0.031%, p=0.181; see Figure).

Conclusion:
Our data demonstrate an increase in the number of AF admissions but constant length of stay and mortality over time. Opportunities to decrease the cost of inpatient AF management should therefore target reducing both the number of admissions as well as the length of stay.
Abstract 11257: Physiologic Quantification of the Diastolic Pressure Difference Re-classifies Pulmonary Hypertension in Patients With Advanced Heart Failure
Authors: Wright Stephen P , Paradero Geraldine , Agarwal Suhail , Moayedi Yas , Foroutan Farid , Alba Ana Carolina , Baumwol Jay , Mak Susanna
Published: April 2024

Introduction:
Assessment of pulmonary hypertension (PH) by right heart catheterization remains important in the evaluation of advanced heart failure (HF) patients being considered for cardiac transplant. Delineating ‘isolated’ post-capillary PH (Ipc-PH) and ‘combined’ pre- and post-capillary PH (Cpc-PH) remains a challenge in hemodynamic assessment, as the usual practice of calculating the diastolic pressure difference (DPD) has limitations pre-disposing it to underestimation.

Hypothesis:
QRS-gated calculation of the DPD (QRS-DPD), specific to late diastole when the DPD is expected to be small, will reduce the frequency of negative DPD values, and re-classify a subset of patients as Cpc-PH.

Methods:
Advanced HF patients (n = 136, median age = 56 years) referred for right heart catheterization within the clinical evaluation for cardiac transplant candidacy were studied. Hemodynamics were analyzed offline and measurements were averaged over 8-10 beat intervals. Automated measurements of systolic/diastolic/mean pulmonary artery pressure (sPAP/dPAP/mPAP), and mean pulmonary artery wedge pressure (mPAWP) were generated as per usual practice. Usual practice DPD (UP-DPD) was calculated as [dPAP – mPAWP]. Within the same intervals, pulmonary artery pressure (QRS-PAP) and pulmonary artery wedge pressure (QRS-PAWP) gated to the QRS-onset were manually measured for each beat and averaged. QRS-DPD was calculated as [QRS-PAP – QRS-PAWP].

Results:
The mean UP-DPD was 0 ± 5 mmHg, and was <0 mmHg in 61/136 cases (45%). The mean QRS-DPD was 5 ± 4 mmHg, and was <0 mmHg in 10/136 cases (7%) (p < 0.05). Of 136 cases, 67 (49%) demonstrated mPAP ≥25 mmHg and mPAWP >15 mmHg. Using the UP-DPD classified 4/67 as Cpc-PH (DPD ≥7 mmHg), while the QRS-DPD classified 22/67 as Cpc-PH (p < 0.05).

Conclusions:
QRS-gated measurements increase the calculated DPD, and reduce the frequency of negative values. In advanced HF patients with PH, up to 25% of Ipc-PH cases may be re-classified as Cpc-PH.
Abstract 11409: Kappa-opioid Stimulation Following Chronic Cardiac Pressure Overload Increases Endothelial Caveolae Formation and Benefits Cardiac Function
Authors: Zemljic-Harpf Alice E , Deussen Daniel N , Joshi Mugdha A , Alas Basheer F , Vainshnav Yash J , Mahata Sushil K , Roth David M , Patel Hemal H
Published: April 2024

Activation of kappa (κ) -opioid receptors (OR) protects from cardiac ischemia reperfusion injury. A critical role for caveolae in opioid mediated cardio-protection has been shown but these findings have not extended beyond the myocyte. The rationale here was to test if chronic κ- OR activation ameliorates pressure overload induced heart failure after transverse aortic constriction (TAC) and determine potential molecular mechanisms. Ten week-old male C57BL/6J mice underwent TAC or Sham surgery. Cardiac function was assessed by echocardiography before TAC/Sham, and consecutively at weeks 2, 4, 6, 8 and 10 to determine cardiac function (%EF), and wall thicknesses (LVPWd). Two weeks after TAC/Sham, daily i.p. injections with a selective κ-OR, U50488H (U50, TOCRIS®, 1.25mg/kg, IP), or vehicle (V, ddH
2
O) were started. Eleven weeks post-TAC (pTAC), hearts were analyzed by transmission electron microscopy (TEM, n=2 each) and immuohistochemistry (n=4 each). Four weeks pTAC LVPWd in TAC+U50 mice were increased compared to TAC+V, and %EF unchanged (mm±SEM; Sham+V 0.67±0.01, TAC+V 0.81±0.02, Sham+U50 0.66±0.01,TAC+U50 0.93±0.03, n=6-7, p <0.007). Ten weeks pTAC %EF was reduced in TAC+V compared to Sham+V, but preserved in TAC+U50 hearts compared to Sham+U50 (%EF±SEM; Sham+V 68.9%±1, TAC+V 49.5%±8; Sham+U50 73.6%±1.7,TAC+U50 65.3%±6, ns; p<0.02; n=6-7each). Eleven weeks pTAC, TEM revealed preserved mitochondrial utrastructure, and electron dense intercalated discs in pTAC+U50 animals. TAC+V hearts showed “bleached” intercalated discs and swollen mitochondria. U50 increased endothelial caveolae formation in Sham+U50 and TAC+U50 hearts (Cav/μm, 13.3 fold upregulation in Sham+U50 vs Sham+V; and a 3.7 fold increase in TAC+U50 vs TAC+V, p<0.004, 15 cells/heart). Immunohistochemical analysis revealed intracellular accumulation of connexin-43 in TAC+V treated mice, but connexin-43 localization was preserved to membranes in TAC+U50 hearts. We show for the first time that chronic κ-OR activation via U50,488H increased caveolae formation in cardiac endothelial cells, improved cardiac ultrastructure and prevented pressure overload induced heart failure. U50,488H administration may offer a novel treatment option in patients prone to heart failure.
Abstract 11413: Appearance of QRS Fragmentation Late After Atrial Switch Repair for d-Transposition of the Great Arteries is Associated With Adverse Clinical Outcome
Authors: Helsen Frederik , Vandenberk Bert , De Meester Pieter , Van De Bruaene Alexander , Gabriels Charlien , Troost Els , Gewillig Marc , Meyns Bart , Willems Rik , Budts Werner
Published: April 2024

Introduction:
The extent of myocardial fibrosis on magnetic resonance imaging (MRI) in the systemic right ventricle (RV) of adults after atrial switch repair for d-transposition of the great arteries (d-TGA) correlates with outcome. However, MRI is costly and access is limited. Fragmented QRS (fQRS) on a 12-lead electrocardiogram (ECG) reflects inhomogeneous ventricular activation. It is considered to be a surrogate for fibrosis and related with outcome in ischemic cardiomyopathy.

Hypothesis:
Appearance of fQRS during follow-up is a predictor for adverse events in adults after atrial switch repair for d-TGA.

Methods:
Records of adults with atrial switch repair for d-TGA were retrospectively reviewed in the database of a tertiary care hospital. Exclusion criteria were systemic RV assist device or heart transplantation (HTx) before the age of 16 years, or fQRS already present at transfer from the pediatric department. One blinded reader analyzed all available ECGs to detect fQRS. fQRS, severe tricuspid regurgitation (TR), severe RV dysfunction and severe RV dilatation were modeled as time-dependent covariates. Cox regression was performed to assess the relationship between covariates and (1) the composite endpoint of cardiovascular mortality, HTx or systemic RV assist device, and (2) worsening RV function.

Results:
Records of 89 patients (34% female, 42% Mustard repair) were analyzed. Patients underwent atrial switch repair between Oct 1969 and Nov 1992. At latest follow-up, fQRS was noted in 26 patients (29%), most frequently inferior (92%). Over a median follow-up of 16.9 (IQR 12.6-22.9) years, the composite endpoint occurred in 9 patients (10%). In multivariate Cox analysis, appearance of fQRS (HR 14.11; 95% CI 1.42-140.12) and development of severe RV dysfunction (HR 11.36; 95% CI 2.08-62.17) were significantly associated with the composite endpoint. Moreover, appearance of fQRS was significantly associated with worsening RV function (HR 2.66; 95% CI 1.18-6.01), independently of development of severe TR.

Conclusions:
Appearance of fQRS is associated with adverse clinical outcome and worsening RV function in adults after atrial switch repair for d-TGA. It might become an easily implementable tool to identify patients at risk for adverse events.