bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12729: Comparisons of Peak LDL-C Reduction and Duration of Effect With Lower or Higher Dosing Regimens of the PCSK9 Inhibitor Evolocumab
Authors: Koren Michael J , Doshi Sameer , Castro Rita , Gibbs John P , Emery Maurice G , Somaratne Ransi , Wasserman Scott M
Published: April 2024

Introduction:
Recent studies of anti-PCSK9 antibodies have established this new class as highly effective in lowering LDL-C and well tolerated with or without background statins. Because peak LDL-C responses to anti-PCSK9 antibodies are not linearly dose-proportional, understanding the pharmacodynamic profile of the therapy can help select optimal dosing. Consequently, we assessed the peak LDL-C effects of 3 evolocumab doses during ongoing therapy and the persistence of effects after 2 weeks when the next dose would be due.

Methods:
In the 12 week Phase 2 LAPLACE-TIMI 57 study 107 patients underwent assessments at weeks 9 and 11 in addition to the usual biweekly lipid measurements at weeks 8 and 10. We analyzed data from patients who received evolocumab 70 or 140 mg Q2W or 420 mg QM for PCSK9 suppression and peak LDL-C effectiveness estimated to occur 1 week post dosing. Persistence of the LDL-C lowering effect over the next week was also assessed.

Results:
The Figure shows PCSK9 and LDL-C over the analyzed interval. Mean baseline LDL-C in these groups was about 130 mg/dL. Week 8 LDL-C representing steady state trough effects were 85.4 mg/dL (35% below baseline), 47.1 mg/dL (62% below baseline) and 52.8 mg/dL (52% below baseline) for 70 and 140 mg Q2W and 420 mg QM, respectively. Week 9 LDL-C for the 70 and 140 mg doses reflected reductions from baseline of 55% and 70%, respectively and an additional -29% and -22% from trough levels. The offset from maximum LDL-C lowering at week 9 to week 10 for Q2W regimens showed mean LDL-C increases of 25.4 mg/dL in the 70 mg group and 6.3 mg/dL in the 140 mg group. No offset was seen in the 420 mg group during weeks 9-10. LDL-C variability was greatest for 70 mg Q2W over the studied dosing interval.

Conclusions:
During steady state dosing of evolocumab on stable statin therapy, dose escalations affect the duration of the LDL-C lowering response more than the peak effect. Higher doses result in less fluctuation in LDL-C response, which may be a goal of therapy.
Abstract 12735: Potential of the Single Beat Estimation for End Systolic Pressure-Volume Relation in Patients With Single Ventricular Heart
Authors: Saiki Hirofumi , Kuwata Seiko , Kurishima Clara , Masutani Satoshi , Senzaki Hideaki
Published: April 2024

Background:
Estimation of ventricular elastance at the aortic valve opening is fundamental for assessment of non-invasive end-systolic elastance (Ees). Despite conditional variability of time varying elastance (Et) property, the Et during isovolumic contraction (IVC) is less variable and highly adjustable, thus Et has been used to estimate Ees in a number of clinical studies. However, uncertain characteristics of Et due to morphological diversity hindered its application in single ventricular hearts (SV). We tested our hypothesis that Et in early systole is independent of ventricular morphology in SV patients.

Methods:
During cardiac catheterization, a total of 78 pressure volume relationships were constructed from 26 children including 18 Fontan patients (right dominant: SRV n=8, left dominant: SLV n=10) and controls (n=8). Et curve, normalized both for Ees and time to Ees, was compared among groups at baseline, dobutamine infusion (DOB, 5 mcg/kg/min) and rapid supraventricular pacing.

Results:
Shapes of Et in SRV and SLV at both baseline and DOB were similar, particularly during IVC and ejection phase (Figure). While Et was stable during pacing with additional 20-30 bpm to the baseline heart rate (HR), relaxation delay caused disturbance of Et in some patients at HR greater than 170 bpm. The slope ratio (α) of Et during ejection phase to that during IVC, which determines subtle variations of Et, was significantly correlated with ejection fraction (EF, R=.65, p<.01) and independent of ventricular type, preload and afterload.

Conclusion:
Et properties in Fontan patients, both with SRV and SLV, highly resemble those in controls at baseline, with DOB, and physiological pacing during systole. Similar to structurally normal hearts, α can be predicted by EF. While impact of diastolic property on early systole should be accounted for in high HR patients, our results rationalized the utility of normalized Et that provides a fulcrum point to estimate Ees in Fontan circulation.
Abstract 12740: CPR Training in Schools: What Can be Learned From Iowa’s Experience?
Authors: Hoyme Derek B , Atkins Dianne L
Published: April 2024

Introduction:
Survival from out of hospital cardiac arrest has remained almost constant at 10-12% over several decades. In a witnessed arrest, prompt initiation of bystander CPR has been demonstrated to double the chance of survival. Overall CPR training rates in the United States are low: 2.4% per year. Currently, 21 states have adopted legislation to increase CPR training in schools. Iowa has required CPR as a high school graduation requirement since 2011 through an unfunded mandate. The objective of this study is to understand the implementation process, practices and barriers to providing CPR education to high school students. We surveyed Iowa high schools to provide guidance for nascent programs based on 4 years of experience.

Methods:
A cross-sectional study was performed through surveys sent to 346 Iowa high schools using the Qualtrics™ online platform. A 20 question survey was developed to obtain descriptive data covering general demographics of the school, specifics of the CPR training programs including what year the program was implemented, who performs the training and in which setting it occurs, logistics and barriers to implementation, and AED training and availability.

Results:
Response rate was 24.3%, with a mean school size of 100-500 students and a mean faculty size of 25-50. When the law took effect in 2011, 51% of schools had training programs already in place, and currently 96% have successfully implemented CPR training. Perceived barriers to implementation were staffing, time commitment, cost, and equipment availability. The training facilitator was a school official or unpaid volunteer in 81% of schools, only 19% reported a paid instructor. Average estimated time commitment was 2 hours. The average estimated startup costs as well as yearly maintenance costs were <$500 with funds usually allocated from existing school district funds. A low proportion of staff is trained in CPR: 69% of schools have less than 25 staff members who are CPR trained. AEDS are available in 98% of schools while only 61% include AED training in their training curriculum.

Conclusions:
Despite perceived barriers, school CPR training programs can be implemented with reasonable resource and time allocations.
Abstract 12766: Dissection of the Interventricular Septum: Echocardiographic Features
Authors: Gu Xiaoyan , He Yihua , Luan Shurong , Zhao Ying , Nixon J V (Ian)
Published: April 2024

Objective:
Dissection of the interventricular septum (IVS) is an extremely rare entity. An institutional data base review identified 13 pts with the diagnosis, confirmed by cardiac surgery. The purpose of the study was to determine the value of transthoracic echocardiography (TTE) in establishing the diagnosis and to summarize the TTE features of IVS dissection.

Methods:
The 13 pts with IVS dissection, 8 males and 5 females (age range: 36-75 yrs) were taken from 789,114 TTEs performed between 1985 and 2014. The etiology, anatomical location, echocardiographic morphology, and color Doppler findings of the IVS dissection were noted.

Results:
The incidence of IVS dissection in our center was 0.000016 %. Among 13 patients with IVS dissection, the right sinus of Valsalva (RSOV) was involved in 11 pts. In 5 pts, a single aneurysm of the RSOV dissected into the IVS. In 4 pts, aortic valve (AoV) endocarditis was associated with the IVS dissection, including one pt with a bicuspid AoV infection, 2 pts with absess formation adjacent to an AoV replacement, one pt. with a combination of a bicuspid AoV and RSOV dissecting into the IVS, and one pt with an AoV prosthetic paravalvular leak following absess formation dissecting into the IVS. In one patient, a bicuspid AoV valve combined with RSOV dissected into the IVS. Also, in one pt, mechanical AoV prosthetic replacement was complicated by annular detachment and a severe paravalvular leak. In all 11 pts with RSOV involvement, TTE showed a dissecting cystic-like mass in the IVS from the base to mid-septum or confined to the septal base. The path of the dissection in all these pts was traced to the RSOV. Also, communications between the dissection and the aortic root were seen in these 11 patients. In the other 2 pts, IVS dissection followed septal rupture due to a myocardial infarction. In these pts, communication between the dissection and the right ventricle was seen.

Conclusions:
The study showed that dissections of the IVS usually commenced in the RSOV, due to either congenital anomalies or infective endocarditis, or following AoV replacement. The other cause of IVS dissection is a myocardial infarction. The TTE characteristic of IVS dissection is a cystic-like mass in the IVS.
Abstract 12781: Traffic-related Air Pollution, Blood Pressure, and Adaptive Response of Mitochondrial Abundance
Authors: Zhong Jia , Cayir Akin , Trevisi Letizia , Sanchez-Guerra Marco , Lin Xinyi , Peng Cheng , Bind Marie-Abèle , Prada Diddier , Laue Hannah , Brennan Kasey , Sparrow David , Vokonas Pantel , Schwartz Joel , Baccarelli Andrea
Published: April 2024

Introduction:
Black carbon (BC) exposure - a tracer of vehicular traffic pollution - is associated with increased blood pressure (BP). Identifying biological factors that attenuate BC effects on BP can aid effective prevention.

Hypothesis:
We aimed to evaluate the role of mitochondrial abundance, an adaptive mechanism compensating for cellular-redox-unbalance, in the BC-BP relationship.

Methods:
At one or more visits among 675 older men from the Normative Aging Study (1,252 observations), we assessed BP and ambient BC levels (2-day to 28-day prior to visit, from a stationary monitor). Mitochondrial abundance was determined as blood mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA) using quantitative polymerase-chain-reaction.

Results:
Every standard deviation (SD) increase in 28-day BC moving average (MA) was associated with 1.94 mm Hg (95%CI, 1.23-2.72; P<0.0001) and 3.46 mm Hg (95%CI, 2.06-4.87; P<0.0001) higher diastolic and systolic (SBP) BP, respectively. Positive BC-BP associations existed throughout all time windows. Likewise, BC MAs (5-day to 28-day) were associated with increased mtDNA/nDNA. Every SD increase in 28-day BC MA was associated with 0.12 SD (95%CI, 0.03-0.20; P=0.007) higher mtDNA/nDNA. High mtDNA/nDNA significantly attenuated the BC-SBP association throughout all time windows. The estimated effect of 28-day BC MA on SBP was 1.95-fold larger for individuals at the lowest mtDNA/nDNA quartile midpoint (4.68 mm Hg; 95%CI, 3.03-6.33; P<0.0001), compared to the top quartile midpoint (2.40 mm Hg; 95%CI, 0.81-3.99; P=0.003).

Conclusions:
In older adults, short- to moderated-term ambient BC levels were associated with increased BP and mitochondrial abundance. Increased mitochondrial abundance may represent a compensatory response that attenuates the adverse cardiac effects of BC.
Abstract 12864: Impact of Calcification Severity on Clinical Outcomes Following Endovascular Therapy in the Patients With Peripheral Artery Disease Presenting With Superficial Femoral Artery Lesions
Authors: Okuno Shota , Fujita Masashi , Iida Osamu , Masuda Masaharu , Okamoto Shin , Ishihara Takayuki , Nanto Kiyonori , Kanda Takashi , Shiraki Tatsuya , Sunaga Akihiro , Tsujimura Takuya , Matsuda Yasuhiro , Yanaka Koji , Ohashi Takuya , Uematsu Masaaki
Published: April 2024

Background:
Although vessel calcification results in poor clinical outcomes following endovascular therapy (EVT) in patients with peripheral artery disease (PAD), the Impact of calcification severity on clinical outcomes remains unclear.

Methods:
A total of 394 consecutive patients (mean age 72.4±8.3 years; 74 % male) with PAD who underwent EVT for de novo superficial femoral artery lesions in our hospital from January 2010 to December 2013 were retrospectively analyzed. These patients were stratified into three groups by fluoroscopy and digital subtraction angiography in the AP projection (no calcium group: no visible calcium at the lesion, unilateral group: unilateral calcification at the lesion, bilateral group: bilateral calcification at the lesion). The primary outcome measure was primary patency, while the secondary outcomes were survival and major adverse limb event (MALE). Cox proportional hazard analysis was performed to explore if this classification was an independent predictor of primary patency.

Results:
224 (57 %) patients had diabetes, 83 (21 %) were on hemodialysis. Prevalence of TASC C/D was 50% (199 of 394) and prevalence of three groups; no calcium, unilateral and bilateral, was 55% (214 of 394), 28% (110 of 394), 17% (70 of 394), respectively. Mean lesion length and reference vessel diameter at the treated segment was 152.1±95.7 mm and 5.7±0.9 mm. Primary patency at 2 year was 70.0% in no calcium group, 68.9% in unilateral group, and 45.8% in bilateral group, respectively; survival rate at 2 year was 96.4% in no calcium group, 94.6% in unilateral group, and 87.4% in bilateral group, respectively; MALE at 2 year was 1.3% in no calcium group, 4.0% in unilateral group, 8.2% in bilateral group, respectively. Bilateral calcification was an independent predictor of primary patency, as were lesion length, lesion diameter and stent use.

Conclusions:
Bilateral calcification was independently associated with primary patency, MALE and survival after EVT.
Abstract 12891: Predictors of Net Adverse Cardiovascular Events in Patients on Triple Antithrombotic Therapy
Authors: Singh Kuljit , Fu Angel , Abunassar Joe , Malhotra Nikita , Hibbert Benjamin , Chong Aun Y , So Derek
Published: April 2024

Introduction:
Patients on dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) often have indications for concurrent oral anticoagulation or triple antithrombotic therapy (TT). While TT may decrease ischemic complications, it may confer increased bleeding risk.

Hypothesis:
We set to determine predictors of complications in patients on TT. In particular, we sought to determine if use of ticagrelor in TT is associated with higher complications.

Methods:
Patients discharged on TT after PCI were followed prospectively for 12 months. The primary endpoint was a composite of ischemic (death, myocardial infarction, stroke) and bleeding (Bleeding Academic Research Consortium (BARC)) complications or net adverse clinical event (NACE). A major secondary endpoint was BARC Types 2, 3 or 5 bleeding. Outcomes were compared between ticagrelor and clopidogrel treated patients. Multivariable analyses were performed to elucidate predictors of complications.

Results:
Twenty-seven of 152 patients discharged on TT were on ticagrelor. NACE occurred in 52% and BARC 2, 3 or 5 bleeding occurred in 18% of patients. There was no difference in the primary or secondary outcome between ticagrelor versus clopidogrel sub-group. On multiple logistic regressions (Figure 1 and 2), use of TT in patients with acute coronary syndrome (ACS) (p = 0.002) and bridging in with ticagrelor (p=0.02) was associated with increased NACE. Low eGFR was an independent predictor of bleeding (p = 0.03).

Conclusions:
From our analysis ticagrelor was not found to be an independent predictor of higher bleeding in TT. Instead, low eGFR is associated with higher risk of bleeding. Use of bridging anticolagulation with ticagrelor is associated with higher NACE.
Abstract 13039: Uric Acids and Risk of Development of Atrial Fibrillation
Authors: Yagihara Nobue , Watanabe Hiroshi , Watanabe Toru , Aizawa Yoshifusa , Minamino Tohru
Published: April 2024

Background:
Uric acid is a final product of xanthine oxidase pathway and is positively correlated with levels of oxidative stress and inflammation, both of which are the important pathogenesis of atrial fibrillation. We aimed to study the impact of serum uric acid level on risk of development of atrial fibrillation in the general population.

Methods:
This prospective observational cohort study was based upon an annual health check-up program including a detailed medical history, physical examination, blood and urine examination, chest x-ray, and a 12-lead electrocardiogram. We included 23,436 individuals (8,611 males; age, 61±12 years) without atrial fibrillation at baseline who were followed for more than one year.

Results:
During a follow up of 6.5±1.9 years, atrial fibrillation developed in 426 individuals (incidence, 2.78 per 1000 person-years; 95% confidence interval [CI], 2.52 to 3.05 per 1000 person-years). Incidence of atrial fibrillation increased with an increasing quartile of serum uric acid levels (Table). In multivariate analysis, elevated serum level of uric acid was independently associated with increased risk of development of atrial fibrillation (hazard ratio [HR], 1.127 per 1.0 mg/dL increase; 95% CI, 1.041-1.219 per 1.0 mg/dL increase). Hyperuricemia defined as serum uric acid more than 7.0 mg/dL was associated with risk of atrial fibrillation (hazard ratio [HR], 1.592; 95% CI, 1.127 - 2.249). The impact of hyperuricemia on risk of atrial fibrillation was higher in women than men.

Conclusion:
Hyperuricemia was a potentially modifiable risk factor for atrial fibrillation. Our study indicates the possibility that interventions to decrease uric acid may reduce the population of atrial fibrillation.
Abstract 13046: Treat and Repair Strategy in Patients With Atrial Septal Defect and Severe Pulmonary Arterial Hypertension
Authors: Akagi Teiji , Kijima Yasuhumi
Published: April 2024

Introduction:
An effective therapeutic strategy in patients with atrial septal defect (ASD) and significant pulmonary arterial hypertension (PAH) remains controversial.

Hypothesis:
PAH-specific medications contribute to improvement of PAH. Subsequent transcatheter ASD closure may lead to further reduction of PAP.

Methods:
Among 646 patients with ASD, 22 who were complicated by definite PAH had successful transcatheter ASD closure. Among them, eight patients received PAH-specific medications prior to the transcatheter procedure (PHM group) and 14 patients did not (non-PHM group).

Results:
The mean age at the procedure in the PHM group was 37±15 years. Initially, the PHM group had significantly higher mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) compared with the non-PHM group (62±21 vs. 35±8 mmHg, p<0.01; 9.6±3.8 vs. 4.1±1.1 Wood units, p<0.01). PAP and PVR in the PHM group significantly decreased to 41±10 mmHg (p<0.01) and to 4.0±0.8 Wood units (p<0.01), respectively, after treatment with PAH-specific medications. In the PHM group, after ASD closure, further reduction of estimated systolic PAP was observed (72±19 to 41±11 mmHg, p<0.01).

Conclusions:Treat and repair is a valid therapeutic strategy for patients with ASD and significant PAH.
Abstract 13100: Thyroid Dysfunction, Cardiovascular Risk Factors, and Incident Cardiovascular Events: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Martin Seth S , Daya Natalie , Lutsey Pamela L , Matsushita Kunihiro , Fretz Anna , McEvoy John W , Blumenthal Roger S , Coresh Josef , Steffes Michael W , Greenland Philip , Kottgen Anna , Selvin Elizabeth
Published: April 2024

Introduction:
Data remain inconclusive on the relation of thyroid dysfunction to atherosclerotic cardiovascular disease risk, particularly with respect to stroke. In addition, prior studies have lacked measurement of T3, the final active form of thyroid hormone.

Methods:
We examined the cross-sectional and prospective associations of thyroid dysfunction with cardiovascular risk factors and events in the community-based ARIC Study. Participants had thyroid measures obtained in an ancillary study at visit 2 (1990-92) and were free of pre-existing cardiovascular disease. We evaluated thyroid function using clinical categories and also log-transformed T3. Cross-sectional outcomes were hypertension, diabetes, and dyslipidemia. Prospective outcomes were adjudicated fatal and non-fatal myocardial infarction and stroke, which are the outcomes of the 2013 ACC/AHA guidelines.

Results:
Among 11,359 participants (mean age 57±6 years, 58% women), 2.2% had overt hypothyroidism, 4.8% subclinical hypothyroidism, 3.3% subclinical hyperthyroidism, and 1.8% overt hyperthyroidism. Compared with euthyroidism, all thyroid dysfunction groups had similar age, sex, and race-center adjusted prevalences of hypertension and diabetes. Regarding dyslipidemia, mean adjusted differences in LDL cholesterol were 15.1 (95% CI 10.5, 19.7) and 3.2 (0.0, 6.4) mg/dL in those with overt and subclinical hypothyroidism relative to euthyroidism; an opposite pattern was seen in overt and subclinical hyperthyroidism [-10.8 (-15.9, -5.7) and -3.9 (-7.7, -0.1) mg/dL, respectively]. During a median follow-up of 20 years, 966 myocardial infarctions and 721 strokes occurred, with no unadjusted or adjusted associations observed with baseline thyroid function groups or by concentration of T3 (Table).

Conclusion:
Thyroid dysfunction is associated with a modest alteration in the lipid profile and no long-term differences in incidence of myocardial infarction or stroke.
Abstract 13266: Non-contrast 3D Magnetic Resonance Imaging Offers and Alternative to Contrast Enhanced Multisclice Computed Tomography for Correct Aortic Valve Sizing in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Bernhardt Peter , Rodewald Christoph , Seeger Julia , Gonska Birgid , Buckert Dominik , Rottbauer Wolfgang , Wöhrle Jochen
Published: April 2024

Introduction:
For successful transcatheter aortic valve implantation (TAVI) correct sizing of the aortic annulus and left ventricular outflow tract in aortic valve stenosis is crucial. With multislice computed tomography (MSCT) 3D volume data sets of the aorta could be acquired in high spatial resolution, but the comorbid patients are exposed to nephrotoxic contrast agents leading to kidney injury in many cases.

Hypothesis:
The purpose of this study was to establish a useful method for sizing for TAVI without the use of contrast media. With MSCT serving as a the reference standard, we compared measurements of a non-contrast 3D steady-state free-precession (SSFP) magnetic resonance (MRI) for correct annulus sizing and decision for valve size.

Methods:
We examined 52 patients previous to TAVI with MSCT using a 256-MSCT and a 1.5 Tesla whole-body MRI scanner, respectively. MRI examination included a 3D SSFP sequence covering the entire ascending aorta. The 3D images of both imaging modalities were reconstructed for correct orthogonal view of the aortic annulus using a dedicated software (3mensio, Pie Medical Imaging, The Netherlands). Minimal and maximal annulus diameters, annulus perimeters, and areas of both imaging modalities were analyzed by two blinded and experienced readers in consensus. Virtual decision for valve size (Edwards Sapien 3) was based on the median of these diameters.

Results:
Mean age of the study cohort was 82.2±4.9 years, 32 (61.5%) were female. Log EuroScore was 25.2±4.8%. Mean annulus perimeter measured by MSCT was 76.7±6.9 mm, by MRI 76.5±6.7 mm (r=0.93, p<0.0001). MSCT yielded a mean annulus area of 545.2±49.0 mm2 with good correlation to MRI, which resulted in a mean area of 543.5±47.0 mm2 (r=0.92, p<0.0001). Decision for Sapien 3 valve size showed good correlation between MSCT and MRI (r=0.94, p<0.0001).

Conclusions:
In conclusion, non-contrast 3D SSFP MRI shows good correlation to MSCT in the assessment of the aortic annulus and valve sizing for TAVI. The non-contrast MRI approach might be a reasonable alternative for aortic root sizing before TAVI without the use of nephrotoxic contrast agents, especially in patients with reduced kidney function.
Abstract 13320: Vascular Dysfunction Due to Sheath Insertion Into the Radial Artery
Authors: Nakata Tomoo , Ikeda Satoshi , Koga Seiji , Koide Yuji , Kawano Hiroaki , Maemura Koji
Published: April 2024

Background:
The transradial approach is widely used for coronary procedures. However, this procedure carries a risk of radial artery injury such as dissection, spasm and occlusion. We examined the vascular dysfunction caused by the transradial approach using reactive hyperemia peripheral arterial tonometry (RH-PAT), a recently used technique for evaluating endothelial function in digits, and compared the differences in injuries according to the size of sheath

Mehods:
Forty-three patients receiving transradial catheterization with 4-Fr/5-Fr (non-6Fr; n = 26) sheaths or 6Fr sheaths (n = 17) were enrolled. RH-PAT was evaluated using Endo-PAT2000 in the arm of sheath placement and in the other arm as a control before, at the day and 6 months (n = 16, 6-Fr group; n = 13, non-6-Fr group) after catheterization.

Results:
RH-PAT values decreased from 2.42 ± 0.67 before catheterization to 2.08 ± 0.41 at the day after catheterization in the 6-Fr group (p = 0.03), which was more evident in patients with a longer procedure time (> 90 minutes). On the other hand, the change in the non-6-Fr group was not significant. RH-PAT of control side was unchanged in both groups. At 6 months after catheterization, RH-PAT values in 6-Fr group had not completely returned to baseline.

Conclusions:
The insertion of a 6-Fr catheter sheath into the radial artery, especially with a longer procedure time, impaired vascular endothelial function, which occurred at the day after the procedure and sustained after 6 months. Thus, we have to pay attention to the sheath size and procedure time at the transradial approach.
Abstract 13374: Efficacy and Safety of K-877, a Potent and Selective PPAR-α Modulator (SPPARMα), in Combination With Statins in Japanese Patients With Dyslipidemia
Authors: Arai Hidenori , Ishibashi Shun , Yamashita Shizuya , Araki Eiichi , Yokote Koutaro , Suganami Hideki , Kodama Tatsuhiko
Published: April 2024

Background:
Residual cardiovascular risk remains despite intensive statin treatment. K-877, a Selective PPAR-α Modulator (SPPARMα), has shown significant reductions in atherogenic lipids with fewer adverse effects than existing PPARα agonists. We hypothesized that K-877 in combination with statins may provide further benefit and risk reduction than statins alone in patients with dyslipidemia.

Methods:
This is a multi-center double-blind parallel-group study. A total of 423 patients with fasting high TG (≥200 mg/dL), treated with any statins (stable dosage at least 4 weeks prior to the first screening visit) were randomized to the following 24-weeks treatment groups; placebo (n=108), twice-daily K-877 0.2 mg/day (n=150) and 0.2/0.4 mg/day [patients took 0.2 mg/day, those with TG >150 mg/dL at week 8 were uptitrated to 0.4 mg/day from week 12] (n=165 [n=58]). The primary endpoint was the percentage change of TG from baseline, and rates of adverse drug reactions (ADRs) and adverse events (AEs) were assessed.

Results:
Fasting TG reduction was as follows; placebo: -0.8%, K-877 0.2 mg: -46.8% and K-877 0.2/0.4 mg: -50.8%. K-877 groups had significant reductions compared with placebo (P<0.01). By dose titration at week 12, more patients achieved the target (fasting TG≤150 mg/dL) at week 24 (36.2% in 0.4 mg group and 29.7% in 0.2 mg group). The incidence of AEs/ADRs in K-877 groups was similar to placebo [placebo, K-877 0.2 and 0.2/0.4 mg: 57.4%/15.7%, 56.0%/19.3% and 63.6%/19.4%, respectively]. The study discontinuation rate was also similar across all dosing groups. K-877 reduced liver enzymes compared to placebo [ALT; placebo, K-877 0.2 and 0.2/0.4 mg: -0.9, -12.8 and -8.0 IU/L, respectively] and [γ-GT; -1.8, -42.6 and -40.4 IU/L, respectively]. Severe liver failure, severe renal failure or the rhabdomyolysis were not observed. Frequencies of AEs, such as CK increase and musculoskeletal and connective tissue disorders were comparable to those of placebo.

Conclusions:
K-877 significantly reduced TG concentrations in dyslipidemic patients on stable statin treatment, was well tolerated, and associated with reductions in liver enzymes. Thus K-877 has a favorable profile of efficacy and safety and may be useful to reduce residual risk in dyslipidemic patients.
Abstract 13428: Unveiling the Predictive Mechanisms of Care-seeking Delay in Patients With Acute Myocardial Infarction
Authors: Li Polly W. C. , Yu Doris S. F.
Published: April 2024

Introduction:
Despite decades of research has been conducted to examine the phenomenon of care-seeking delay in patients with acute myocardial infarction (AMI), such delay remains the most significant limiting factor for effective disease management.

Objectives:
This study aimed to develop and test an integrative theoretical model to unveil the predictive mechanism for explaining the care-seeking behaviors of patients who experiencing an attack of AMI.

Methods:
Based on several major theories which explain the illness behaviors of patients with chronic diseases and the research evidence on the care-seeking behaviors of AMI patients, we hypothesized that AMI patients’ care-seeking decision was determined by two sequential perceptual-cognitive processes and the immediate context of symptom occurrence. A total of 301 patients with a recent AMI were recruited from the cardiac units of three regional hospitals in Hong Kong. Structural equation modeling was used to test the validity of the hypothesized model.

Results:
The results indicated the decision-making process of AMI patients was driven by two sequential perceptual-cognitive processes, by which a successful action relied on whether the patients could correctly attribute the symptoms to AMI. Such correct symptom attribution depended upon whether they were aware of their own susceptibility to this condition and had a good understanding about the nature of the disease manifestation. A perception of severe illness consequences and the associated negative emotional arousal motivated patients to seek care. The immediate context in which the symptoms occurred also played a role in influencing their decision making, with the favorable roles of lower level of perceived barriers to seek care and positive cues from others in advising care-seeking. This model explained 46% of the variance of care-seeking behaviors with a good data-model fit (χ2 = 38.48, df=30, p=0.72; RMSEA=0.03, NFI=0.96, NNFI=0.98 and CFI=0.99).

Conclusions:
The integrative theoretical model is valid to explain the care-seeking decisions in AMI patients. This model provides important insights to inform the development of innovative empowerment strategies to enhance appropriate care-seeking decisions and behaviors among AMI patients.
Abstract 13631: Therapeutic Inhibition of Mitochondrial Reactive Oxygen Species With Mito-tempo Reduces Diabetic Cardiomyopathy
Authors: Ni Rui , Peng Tianqing
Published: April 2024

Introduction:
The mitochondria are important sources of reactive oxygen species (ROS) in the heart. Mitochondrial ROS production and subsequent oxidative damage have been implicated in the pathogenesis of diabetic cardiomyopathy. We hypothesized that therapeutic strategies specifically targeting mitochondrial ROS may have benefit in diabetic cardiomyopathy.

Hypothesis:
We hypothesized that therapeutic inhibition of mitochondrial ROS with mito-TEMPO reduces diabetic cardiomyopathy.

Methods:
The mitochondria-targeted antioxidant mito-TEMPO was administrated after diabetes onset in a mouse model of streptozotocin (STZ)-induced type-1 diabetes and type-2 diabetic db/db mice. Cardiac adverse changes were analyzed and myocardial function assessed. Cultured adult cardiomyocytes were stimulated with high glucose, and single mitochondrial superoxide generation and cell death were measured.

Results:
Incubation with high glucose increased mitochondria superoxide generation in cultured adult cardiomyocytes, which was prevented by mito-TEMPO. Co-incubation with mito-TEMPO also abrogated high glucose-induced cell death. Mitochondrial ROS generation, and intracellular ROS formation and oxidative damage were induced in both type-1 and type-2 diabetic mouse hearts. Daily injection of mito-TEMPO for 30 days inhibited mitochondrial ROS generation, prevented intracellular ROS formation and oxidative damage, decreased apoptosis and reduced myocardial hypertrophy in diabetic hearts without change of blood glucose, leading to improvement of myocardial function in both type-1 and type-2 diabetic mice. Mechanistic study revealed that the protective effects of mito-TMEPO were associated with down-regulation of ERK1/2 phosphorylation in diabetic hearts and high glucose-stimulated cardiomyocytes.

Conclusions:
Therapeutic inhibition of mitochondrial ROS by mitochondria-targeted antioxidant mito-TEMPO reduced adverse cardiac changes and mitigated myocardial dysfunction in both type-1 and type-2 diabetic mice. Thus, mitochondria-targeted antioxidants may be an effective therapy for diabetic cardiac complications.
Abstract 13715: Colchicine Acutely Suppresses the NLRP3 Inflammasome in Acute Coronary Syndrome Patients Monocytes
Authors: Robertson Stacy , Payet Cloe , Martinez Gonzalo J , Barraclough Jennifer , Celermajer David , Bursill Christina , Patel Sanjay
Published: April 2024

Objectives:
Inflammasome activation, with subsequent release of pro-inflammatory cytokines IL-1β and IL-18, has recently been implicated in atherosclerosis-associated inflammation. Here, in acute coronary syndrome (ACS) patients, we assessed (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation.

Methods:
ACS patients (n=21) were randomized to oral colchicine (1.5mg) or no treatment, and compared with untreated healthy controls. Venous samples were drawn pre- (day 1) and 24h post- (day 2) treatment. Cultured monocytes were stimulated with ATP which facilitates the release of cleaved cytokines. Analysis of key inflammasome markers was performed in cell media and lysates.

Results:
Monocytes from untreated ACS patients secreted significantly higher levels of cleaved IL-1β and IL-18
vs
healthy controls (p<0.05 for both; Fig A). Colchicine treatment in ACS patients markedly reduced intracellular pro- and cleaved IL-1β protein levels as well as secreted cleaved IL-1β protein levels (Fig A)
vs
pre-treatment levels. Colchicine treatment significantly reduced pro-caspase-1 mRNA levels and secreted caspase1 protein levels (p<0.05) vs untreated patients (Fig B). IL-18 levels were unaffected by treatment. In untreated ACS patients, inflammasome-related protein levels did not significantly change between day 1 and day 2

Conclusion:
We show here, for the first time, that (1) monocytes from ACS patients are “primed” to secrete inflammasome-related cytokines and (2) short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing cellular protein secretion of IL-1β. These data, therefore, provide mechanistic insights into a potential role for colchicine in suppressing coronary inflammation in ACS patients.
Abstract 13951: Right Anterior Oblique in Addition to Left Anterior Oblique Projections Are Useful to Implant Right Ventricular Pacemaker Lead Into Mid-Septum and Achieve More Physiological Pacing
Authors: Tanaka Akihiro , Nishino Masami , Okamoto Naotaka , Mori Naoki , Makino Nobuhiko , Egami Yasuyuki , Shutta Ryu , Tanouchi Jun
Published: April 2024

Introduction:
It has been reported that it is difficult to implant right ventricular (RV) leads to the true mid-septum using conventional fluoroscopic criteria. Thus, we investigated which is the best method to achieve the true RV mid-septum using 3 dimensions (3D) reconstruction of 64-slice multidetector computed tomography (64 MDCT).

Methods and Results:
We retrospectively analyzed 33 patients in whom we intended to place RV lead into the septum using conventional fluoroscopic criteria, 40 degree left anterior oblique (LAO40), and performed 64 MDCT later. 3D reconstruction of 64 MDCT revealed that the right ventricular lead was anchored on the true mid-septum in 10 patients (only 30%; MS group, n=10), anterior wall in 19 patients, and free wall in 4 patients (non-MS group, n=23). After implantation of the pacemaker, we evaluated the predictive value of MS group when we used electrocardiography criteria (q wave or negative QRS complex in lead I), 90 degree left lateral (LL90) view and 30 degree right anterior oblique (RAO30) view using 3D reconstruction of 64 MDCT in addition to LAO view. As shown in a table, the method using both LAO and RAO views was the best to achieve the true RV mid-septum among these methods. MS group had significantly shorter paced QRS duration and ΔQRS (paced QRS-own QRS) than non-MS group (139±21.9ms vs. 155.3±10.9ms, p=0.03 and 24.2±21.2ms vs. 55.5±9.1ms, p=0.0001).

Conclusions:
The true mid-septum RV pacing could achieve more physiological pacing. Not only confirming rightward orientation in LAO view but also aiming the middle of the cardiac silhouette in the RAO view may be a simple and accurate way to achieve the true RV mid-septum positioning.
Abstract 13992: The Impact of Dexmedetomidine on the Cardiac Electrophysiological Properties in Patients With Paroxysmal Atrial Fibrillation
Authors: Sairaku Akinori , Nakano Yukiko , Suenari Kazuyoshi , Kihara Yasuki
Published: April 2024

Background:
Dexmedetomidine (DEX), a selective α2-adrenergic receptor agonist, has increasingly been used as a sedative during ablation of atrial fibrillation. DEX is known to have some suppressive effects on the cardiac conduction system, however, that has not yet been extensively assessed in human adults. We aimed to perform a detailed analysis of the impact of DEX on the cardiac electrophysiological properties in patients with paroxysmal atrial fibrillation (AF).

Methods and Results:
We measured the cardiac electrophysiological properties in adult patients (65±11 years) undergoing ablation of paroxysmal AF who were assigned to receive DEX (10 minutes of a loading at a dose of 6μg/kg/min followed by a maintenance dose of 0.6μg/kg/min; N=120) or those who were assigned not to receive any sedative (N=120). The patients with DEX were more likely than those without to have a longer sinus cycle length (943±190 vs. 802±142ms; p<0.001), greater corrected sinus node recovery time (547±334 vs. 441±239ms; p<0.001), and more prolonged atrial effective refractory period (234±35 vs. 220±33ms; p<0.001). The AH interval (103±24 vs. 91±20ms; p<0.001), atrioventricular (AV) nodal effective refractory period (324±70 vs. 268±58ms; p<0.001), and Wenckebach cycle length (446±76 vs. 377±55ms; p<0.001) were greater in patients with DEX, while the HV interval was similar between the groups (42±11 vs. 41±8ms; p=0.63). AF was less often induced in the patients with DEX than in those without (8.3% vs. 20.8%; p=0.01), when a single extra stimulus was given within the atrial vulnerable period.

Conclusions:
DEX may have inhibitory effects on both the sinus node and AV node, and may even reduce the AF inducibility in adult AF patients.
Abstract 14096: Ischemic Postconditioning During Cardiopulmonary Resuscitation Normalizes Mitochondrial Function in a Porcine Model of Prolonged Cardiac Arrest
Authors: Matsuura Timothy R , Tsangaris Adamantios , Bartos Jason A , Chandra Shekar Kadambari , Olson Matthew D , Rees Jennifer N , McKnite Scott H , Lick Michael C , Cheng Qunli , Neumar Robert W , Bienengraeber Martin , Aufderheide Tom P , Riess Matthias L , Yannopoulos Demetris
Published: April 2024

Introduction:
Mitochondrial dysfunction is a hallmark of prolonged ischemia, however it’s onset during cardiac arrest (CA) and reperfusion with cardiopulmonary resuscitation (CPR) has yet to be elucidated. In a porcine model of CA, ischemic postconditioning (IPC) during CPR increased neurologically intact survival. We hypothesized that reperfusion injury, as evidenced by mitochondrial dysfunction, develops during CPR and is rescued with IPC. We investigated the effect of CA, CPR, and IPC on mitochondrial function and viability.

Methods:
After 15 min of ventricular fibrillation, 30 animals were randomized to no CPR (VF, n=10), active compression decompression + impedance threshold device (ACD-ITD) CPR (Control, n=9), or ACD-ITD CPR + IPC (IPC, n=11). Aortic blood pressure and ECG were continuously recorded. IPC consisted of 3 cycles of 20 sec compression / 20 sec pause for the first 2 min of CPR. Cardiac mitochondria were isolated via differential centrifugation 4 min after initiation of CPR. Additionally, mitochondria were isolated from 6 animals that did not suffer CA (non-ischemic controls). Respiration and calcium retention capacity (CRC) were measured for complex I (pyruvate+malate) and II (succinate+rotenone) substrates. Respiratory control index (RCI) was calculated as the ratio of states 3 to 4 respiration. Data were compared with ANOVA. A p value < 0.05 was considered significant.

Results:
Coronary perfusion pressure was similar between groups during CPR. Compared to the non-ischemic group, VF resulted in decreased complex I and II RCI and decreased complex I CRC. Control CPR increased complex I and II RCI compared to VF but did not affect complex I CRC. IPC increased complex I and II RCI and complex I CRC compared to VF and Control to a level comparable with the non-ischemic group. Complex II CRC was unchanged between groups.

Conclusion:
Complex I and complex II RCI and complex I CRC are diminished during VF. Respiration is partially restored with standard CPR. IPC improved mitochondrial function to non-ischemic values as early as 4 min after initiation of CPR. These improvements were independent of changes in blood pressure, suggesting that initiation of CPR is a source of mitochondrial reperfusion injury and a critical time for intervention.
Abstract 14158: Impact of Statin Following Endovascular Aneurysm Repair in Patients With Abdominal Aortic Aneurysm
Authors: Nanto Kiyonori , Iida Osamu , Fujita Masashi , Masuda Masaharu , Okamoto Shin , Ishihara Takayuki , Shiraki Tatsuya , Kanda Takashi , Sunaga Akihiro , Tsujimura Takuya , Okuno Shota , Yanaka Koji , Matsuda Yasuhiro , Ohashi Takuya , Tazaki Junichi , Uematsu Masaaki
Published: April 2024

Introduction:
Endovascular aneurysm repair (EVAR) has been an established treatment for abdominal aortic aneurysm (AAA). Although statin use has been shown associated with better long-term survival following open AAA surgery, its impact on EVAR has not been systematically explored.

Methods:
We retrospectively analyzed a multicenter database of 368 consecutive patients (age, 76 ± 8 years; 84% male) undergoing EVAR for AAA between November 2006 and December 2013. The outcome measure was overall survival following EVAR. Independent predictor associated with the outcome was assessed by Cox proportional hazard regression model. Furthermore, the association between the statin use and the outcome was assessed.

Results:
During the follow-up of 30 ± 20 months, 38 patients died from cardiovascular disease (33%), cancer (23%) or infection (23%). Survival rate was 96% and 81% at 1 and 5 years, respectively. In Cox regression analysis, statin use (in 213 AAA patients, 58%) was negatively associated with the mortality [HR, 0.34; P = 0.002]. There was a significant interaction effect between statin and preoperative aneurysm size. The adjusted hazard ratio of statin for mortality was 0.19 (95% confidence interval (CI): 0.08 to 0.48, p < 0.001) in patients with preoperative aneurysm size < 55 mm, whereas it was 1.00 (95% CI: 0.31 to 3.19, p = 1.000) in those with preoperative aneurysm size ≥ 55 mm. (Figure)

Conclusions:
In this retrospective study, statin use was associated with a better long-term survival following EVAR for AAA, particularly in those with preoperative diameter <55mm.
Abstract 14239: Trends and Outcomes in Hospitalizations With Acute Diastolic Heart Failure, 2003 to 2012
Authors: Goyal Parag , Almarzooq Zaid I , Sobol Irina , Karas Maria , Singh Harsimran S , Swaminathan Rajesh V , Feldman Dmitriy N , Minutello Robert M , Bergman Geoffrey , Wong S. Chiu , Horn Evelyn M , Kim Luke K
Published: April 2024

Introduction:
Hospitalizations for heart failure with preserved ejection fraction (HFpEF) are increasing. There is limited data examining contemporary trends and outcomes in patients hospitalized with HFpEF.

Hypothesis:
Outcomes in patients hospitalized with HFpEF are improving over time.

Methods:
We examined all hospitalizations with acute heart failure (n=5,829,546) in 2003-2012 using the Nationwide Inpatient Database. Based on ICD-9 codes, we identified 2,329,391 (~40%) as acute diastolic heart failure without concurrent systolic heart failure, or HFpEF. Patient characteristics, in-hospital mortality rates, and length of stay (LOS) were examined.

Results:
Compared to those with heart failure with reduced ejection fraction (HFrEF), those with HFpEF were older (mean 76±13 vs 72±14 years), more likely female (64% vs 42%), and more likely to have hypertension (67% vs 64%), atrial fibrillation (43% vs 39%), chronic pulmonary disease (38% vs 32%), renal failure (36% vs 35%), and anemia (34% vs. 26%) (all p<0.001). Over time, HFpEF comprised increasing proportions of men and patients aged ≥75. Compared to HFrEF, in-hospital mortality rate was lower (4.3% vs 5.1%), and mean LOS was higher in HFpEF (7.0 vs 6.8 days) (both p<0.001). The in-hospital mortality rate for HFpEF declined by 13% from 2003 to 2012 (4.8% to 4.2%, p-for-trend <0.001), reflecting improved survival in females and those aged ≥65 years (both p-for-trend<0.01). Mean LOS declined by 8% (7.4 to 6.8 days, p-for-trend<0.001). Adjusting for potential confounders using multivariate regression analysis, pulmonary circulation disease (OR 1.90, 95%CI [1.86 to 1.94]), liver disease (OR 1.57, CI [1.52-1.63]), and renal failure (OR 1.35, CI [1.33-1.37]) were independent predictors of in-hospital mortality. Whereas atrial fibrillation (OR 1.07 [CI 1.06-1.08]) was mildly associated with in-hospital mortality, traditional factors of hypertension (OR 0.64 [CI 0.63-0.65]), diabetes (OR 0.77 [CI 0.76-0.78]), and CAD (OR 0.79 [CI 0.78-0.80]) were inversely related (all p<0.001).

Conclusions:
Hospitalizations for HFpEF place a significant burden on the U.S. health care system. Our study, which represents the largest cohort of HFpEF to date, shows that outcomes have improved between 2003 and 2012.