bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18661: Endothelial Effects of High-Density Lipoprotein (HDL) Remain Impaired Following Dalcetrapib Treatment in Patients with Coronary Artery Disease or Risk Equivalent
Authors: Riwanto Meliana , Deanfield John , Manz Jasmin , Rohrer Lucia , Suchankova Gabriela , Kallend David , von Eckardstein Arnold , Lúscher Thomas F , Landmesser Ulf
Published: April 2024

Introduction:
As low HDL-Cholesterol levels are associated with an increased cardiovascular risk at least in epidemiology, raising HDL-Cholesterol is being examined as a potentially important therapeutic strategy. However, vascular effects of HDL have recently been found to be highly heterogeneous and benefits may be lost, at least partially, in patients with coronary artery disease (CAD). We therefore studied in patients with CAD or CAD-risk equivalent the effect of the CETP inhibitor dalcetrapib as compared to placebo on HDL function.

Methods:
HDL was isolated by sequential ultracentrifugation from patients randomized to treatment with dalcetrapib (600 mg/day; n=25) or placebo (n=25) at baseline, 12 and 36 weeks, and from healthy subjects. The effect of HDL on endothelial nitric oxide (NO) production was measured by ESR spectroscopy and on endothelial pro-inflammatory and pro-apoptotic activation determined by VCAM-1 and active caspase-3 expression assays, respectively.

Results:
There was no significant improvement in the capacity of HDL to stimulate endothelial NO production following dalcetrapib treatment or placebo in patients with CAD or risk equivalents, that remained impaired as compared to HDL-Healthy. HDL isolated from the dalcetrapib group showed an increase in the capacity to reduce endothelial VCAM-1 activation (9.0±6.3% at 12 weeks, 9.7±6.7% at 36 weeks, vs. 5.3±4.5% at baseline; p<0.05); but remained significantly impaired (HDL-Healthy: 15.2±6.5%; p<0.05). There was also an increase of the capacity of this HDL to reduce active endothelial caspase-3 expression (12.1±8.7% at 36 weeks vs. 6.9±9.9% at baseline; p<0.05); however, these endothelial anti-apoptotic capacities remained largely impaired as compared to healthy subjects (18.9±6.6%; p<0.05).

Conclusions:
Despite a significant increase in HDL-C levels (+31% at 36 weeks), dalcetrapib treatment did not restore the potential anti-atherosclerotic properties of HDL on the endothelium as found in the healthy controls. This finding may contribute, at least in part, to the lack of benefit on endothelial function seen in dal-VESSEL trial and demonstrates the importance of measuring not just HDL-C plasma levels but also its vascular impact when assessing novel treatments.
Abstract 18663: Clinical Risk Profile of Stroke in Hypertrophic Cardiomyopathy: A Case-Matched Study from the Nationwide Inpatient Survey (NIS)
Authors: Vercimak Danika , Duval Sue , Jain Renuka
Published: April 2024

Introduction:
Ischemic stroke complicates hypertrophic cardiomyopathy (HCM), but little is known about the epidemiology of stroke in patients(pts) with HCM as opposed to stroke in pts without HCM.

Methods:
Using administrative data from the Nationwide Inpatient Sample (NIS) in years 2000-2009, we analyzed all cases of acute ischemic stroke and transient ischemic attack (TIA) requiring hospitalization in patients with HCM. We matched these pts by year of admission with a random sample of stroke and TIAs in non-HCM pts.

Results:
We analyzed 540 cases of acute stroke/TIA in pts with HCM compared to 2164 cases of acute stroke/TIA in pts without HCM. Mean age and prevalence of hypertension were similar in both groups (Table). In this population of stroke pts, atrial fibrillation was 3.3 (95% CI 2.6-4.0) times more common in HCM group than non-HCM group. Additional characteristics more common in HCM group were female gender (OR 1.7, 95% CI 1.4-2.0), congestive heart failure (OR 2.0, 95% CI 1.5-2.6), and valvular heart disease (OR 3.4, 95% CI 2.6-4.4). Length of hospital stay was one day longer (5.4 days vs. 4.2 days, p<.0001) and routine discharge to home was less frequent (51.9% vs. 61.1%, p<.01) in the HCM compared to non-HCM group. There was no change in which outcomes were statistically significant after adjusting for age and comorbidity score. However, after controlling for the characteristics that differ significantly between HCM and non-HCM groups in Table 1, routine discharge became statistically non-significant (p<0.07). This was due to the addition of atrial fibrillation to the model. There was no significant difference in in-hospital mortality after stroke.

Conclusions:
In the largest case series accumulated of stroke/TIAs in HCM patients, key differences were seen in the clinical risk profile and outcomes of stroke compared to non-HCM controls. This suggests that a unique approach should be taken in dealing with patients with HCM who suffer from stroke.
Abstract 18685: Global Myocardial Blood Flow Measurements Correlate with Angiographic Severity of Coronary Artery Disease
Authors: Lou Jun-Yang , Tamarappoo Balaji K , Difilippo Frank P , Brunken Richard C , Cerqueira Manuel D , Hachamovitch Rory
Published: April 2024

Background.
The correct identification of multivessel coronary artery disease (CAD) is a potential limitation of routine stress-rest using positron emission tomography (PET) myocardial perfusion imaging .We examined whether PET-based myocardial blood flow (MBF) and flow reserve (MFR) can be used to enhance the identification of extensive CAD.

Methods.
We identified 115 consecutive patients (pts; 65±11 yrs, 75% men) who underwent Regadenoson stress
82
Rb PET and coronary angiography within 6 months. MBF during hyperemia and rest and their ratio (MFR) were quantified. PET metrics included summed rest, stress and difference scores (SRS, SSS and SDS, respectively), transient ischemic dilatation (TID) and changes in ejection fraction (ΔEF). PET results were stratified based on angiographic severity grade from 0 (no stenosis>70% or left main>50%) to 5 (significant 3 vessel and left main CAD) and were analyzed using one way analysis of variance.

Results.
In total, 26 pts had no significant CAD (severity score=0); 27, 30, 22 and 10 patients had severity scores of 1, 2, 3 and 4, respectively. Resting global MBF did not vary as a function of CAD severity (ANOVA F-statistic = 1.63, p = 0.17), where as there was a strong correlation between CAD severity and global MBF during stress (F=13.5, p<0.0001, figure), SSS (F=12.8, P<0.0001) and global MFR (F=10.8, p<0.0001). Weaker correlations were observed between coronary severity and SDS, Delta EF, and TID, respectively (F=8.2, 3.1, and 0.6). In the 35 pts (30% of total) with left main stenosis or 3-vessel CAD, 31 (89%) pts had abnormal stress MBF and MFR (using cut-offs of 1.80 ml/min/g and ratio of 2.0, respectively); whereas 54% had negative [[Unable to Display Character: ▵]]EF and only 20% had abnormal TID.

Conclusion.
Absolute stress MBF and MFR enhance the diagnostic accuracy of cardiac PET over conventional parameters for the identification of high-risk, severe and extensive CAD. This approach may reduce the incidence of CAD underestimation by PET.
Abstract 18689: Building a High-throughput Assay for Arrhythmogenic Cardiomyopathy Modifier Pathways in the Zebrafish
Authors: Plovie Buys Eva , Liu ZhenZhen , Capoen Ward , Asimaki Angeliki , Becker Jason R , Adams Eddie , Kleber Andre G , Saffitz Jeffrey E , MacRae Calum A
Published: April 2024

Introduction:
The arrhythmogenic cardiomyopathies (ACs) are rare inherited heart muscle disorders with a high incidence of ventricular tachyarrhythmias and sudden death. One prominent feature of ACs is variable penetrance that implicates major genetic and epigenetic modifiers of disease expression. We sought to develop a robust model of AC in the zebrafish to enable high-throughput genetic and chemical screens for important modifier pathways in ACs.

Methods and Results:
We generated a zebrafish AC model using cardiac-specific expression of the 2057del2 mutation in human plakoglobin using the GAL4/UAS transactivation system. Plakoglobin mutant fish exhibit a unique phenotype with mild bradycardia, cardiomegaly, and peripheral edema in early adulthood and substantial mortality by the time maturity is reached (survival 45% vs 77% for WT p<0.01). Using qPCR we confirmed an upregulation of natriuretic peptide b (nppb), in mutant expressing fish compared to non-expressing siblings (2 fold, p<0.01). To adapt this line for high-throughput screening, we mated the founders with an existing nppb:luciferase reporter line that we have previously validated and is compatible with 96-well plates. Native nppb expression was strongly correlated with semi-automated luciferase data in this reporter line (average count/embryo ± SEM 202 ± 15 in mutant vs 117 ± 12 in WT, P<0.001). We have gone on to screen a library of 4800 bioactive compounds for disease modifiers and to date have identified both suppressor compounds (10) and compounds that exacerbate the disease response (14). One suppressor of the disease phenotype (SB2) attenuates nppb expression, bradycardia and contractility in the mutant, while also improving survival at 28 days (survival 1.5 μ M SB2 62% and 74% 3 μ M SB2 vs untreated 46%, p<0.01).

Conclusion:
These data support the feasibility of high-throughput approaches to the modeling of complex cardiovascular disorders in zebrafish, as well as the use of such models to identify novel chemical probes and candidate drug leads for major disease pathways. One compound identified in the screen has already demonstrated efficacy in long-term use in AC models. Ultimately, screens of type will enable personalized disease modeling for a broad range of human diseases.
Abstract 18705: Regional Variability of Microcirculatory Resistance After Successful Percutaneous Coronary Intervention
Authors: Iwai Toshiyuki , Masuda Ryo , Takagi Takamitsu , Murai Tadashi , Lee Tetsumin , Kakuta Tsunekazu
Published: April 2024

Background:
The main drawback of Fractional Flow Reserve (FFR) measurements occurs in the presence of microvascular disease, as FFR does not take into consideration the contribution of abnormal microvascular resistance. Normal FFR with concomitant microcirculatory disease may be a cause of angina symptoms or myocardial ischemia. Recently, the blood flow in the myocardium has been reported to show significant spatial heterogeneity. We assessed the hypothesis that heterogeneity of regional microvascular resistance exists in patients after successful percutaneous coronary intervention (PCI).

Methods and Results:
FFR and the index of microcirculatory resistance (IMR) were measured after successful PCI in 20 patients with native de novo discrete coronary lesions both in the territory of the culprit vessel and in the reference territory of non-culprit vessel. Hyperemic mean transmit time (Tmn) was used for the assessment of coronary flow. FFR value after PCI was 0.89 (IQR 0.82-0.96). IMR value in the culprit vessel was 18.8 (IQR 12.1-25.7), and 19.05 (IQR 14.3-26.7) in the non-culprit vessel, respectively. There was no significant relationship between these two regional measurements (r
2
=0.0128, p=ns). Mean difference between these two measures was 17.4 ± 15.9. The coefficients of variation of IMR were 75.7% in the culprit vessel, and 59.5% in the non-culprit vessel. There was a significant relationship between IMR and Tmn both in the culprit vessels (r=0.968, p<0.0001) and non-culprit vessels (r=0.913, p<0.0001).

Conclusion:
A considerable regional heterogeneity of coronary perfusion and microvascular resistance were observed in the present study. There is a high inter-subject, intra-subject, and interregional variability of coronary flow and microvascular resistance in patients after successful PCI. These results highlight the difficulty in establishing the limits of normal microvascular resistance or vasodilating response in patients with ischemic heart disease.
Abstract 18720: Multi Center, Prospective, Randomized, Single Blind, Consecutive Enrollment Evaluation a Novolimus-Eluting Coronary Stent System with Bioabsorbable Polymer Compared to a Zotarolimus-Eluting Coronary Stent System: 12- Month Clinical and 6-Month Angiographic and IVUS Results: the EXCELLA BD Study
Authors: Abizaid Alexandre , Schofer Joachim , Botelho Roberto , Verheye Stefan , Costa Ricardo , Tanajura Luiz Fernando , Waseda Katsuhisa , Morrison Lynn , Toyloy Sara , Fitzgerald Peter
Published: April 2024

Aims:
To evaluate the safety and effectiveness of the Elixir DESyne
TM
BD Novolimus Eluting Coronary Stent System (CSS) with a bioabsorbable polymer compared to the Endeavor Zotarolimus Eluting Coronary Stent System through the assessment of clinical, angiographic, and IVUS endpoints.

Method and Results:
149 patients were randomized 3:1, either to the Elixir DESyne BD Novolimus Eluting CSS loaded with 5mcg per mm of stent length of Novolimus, a sirolimus metabolite, eluted via a bioabsorbable polylactide-based polymer, or to the Endeavor Zotarolimus-eluting CSS loaded with 10mcg per mm of stent length of Zotarolimus eluted via a durable phosphoryl choline polymer. All patients were analyzed for the primary endpoint of in-stent late lumen loss (LLL) assessed by QCA at 6 months. Moreover, all patients underwent evaluation for the secondary endpoints including the Device-orientated Composite Endpoint (DoCE) defined as: cardiac death, MI not clearly attributable to a non-intervention vessel, and clinically-indicated target lesion revascularization; clinically-indicated Target Vessel Revascularization (TVR), and stent thrombosis at 1, 6, 9, and 12 months and annually through 5 years. Lesions were also evaluated for angiographic endpoints at 6 months including: in-segment LLL, percent diameter stenosis, minimal lumen diameter post-procedure and at 6 months, and angiographic binary restenosis (ABR) (≥50%). A subset of patients underwent intravascular ultrasound (IVUS) evaluation including percent (%) neointimal obstruction at 6 months. The study met the primary endpoint demonstrating both non-inferiority and superiority of the DESyne BD compared to the control (0.12±0.15 vs 0.67±0.47, p<0.001), additionally, in-stent ABR was significantly lower for DESyne BD (0% vs 7.9%, p=0.003). Excellent clinical results at 6 months were demonstrated for both devices. Clinical results through 12 months and additional angiographic and IVUS results will be presented.

Conclusion:
Clinical results through 12 months and complete angiographic and IVUS results will be presented.
Abstract 18761: Improved Quality of Life and Functional Capacity for Patients Receiving the HVAD
®
Pump
Authors: Birks Emma J , Slaughter Mark S , Boyce Steven W , McGee Edwin C , Cotts William G , Najjar Samer S , Pagani Francis D , Hathaway David , Jacoski Mary V , Najarian Kevin B , Aaronson Keith D
Published: April 2024

Background: Patients with advanced heart failure experience significant impairment in quality of life (QoL) and functional capacity. Improved survival and longer waits for transplant following LVAD implantation means QoL and functional capacity outcomes are increasingly important. We reviewed the experience of patients receiving the HeartWare
®
Ventricular Assist System (HVAD), a novel design continuous flow, centrifugal pump in the pivotal ADVANCE Bridge to Transplant (BTT) Trial and Continued Access Protocol (CAP) to explore changes in QoL and functional capacity.

Methods: The QoL surveys analyzed in the combined BTT and CAP trials included the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary, and the EuroQOL-5D Visual Analog Scale (VAS). The 6 minute walk test (6MW) was used to determine functional capacity. Descriptive statistics were used to evaluate differences compared to baseline.

Results: In the combined BTT and CAP study (N=332), between 44% and 55% of patients completed paired QoL measurements, at baseline (pre-implant) and 180 days post-implant. Patients unable to complete a test for any reason other than incomplete follow-up visit had imputed values of zero. Of 231 patients who were available for follow-up at 6 months (i.e., not transplanted, explanted for recovery, or dead and had reached the 6 month post-implant assessment), paired data were obtained on 184, 164 and 146 patients for the 6MW, KCCQ and VAS, respectively. Of patients completing the paired assessments, there was a statistically significant improvement of 195.9 meters in the 6 Minute Walk Test. Both the EQ-5D Visual Analog Scale and KCCQ Overall Summary also showed statistically significant improvements in their scores of 27.0 and 31.1 points, respectively.

Conclusion: QoL and functional capacity was substantially improved at 6 months in bridge to transplant recipients of the HeartWare HVAD System.
Abstract 18768: Comparison of Displacement-Based and Radial Uniformity Ratio Estimate Dyssynchrony Metrics in Serial Echocardiography of Post-Infarct Mice
Authors: Lin Dan , Xu Yaqin , French Brent A , Hossack John A
Published: April 2024

Background:
Many of the existing dyssynchrony metrics rely on myocardial strain measurements, including circumferential uniformity ratio estimate (CURE) and related metrics such as RURE. Since strain is a derivative of displacement, amplification of noise in strain calculations due to noisy displacement data is common, thus compromising strain-based dyssynchrony metrics. We propose a novel displacement-based dyssynchrony metric, called Dyskinesia Index (DI), that is sensitive and consistent in detecting left ventricular (LV) dyssynchrony, particularly dyskinesia.

Methods:
Long-axis (LA) cines of 7 C57BL/6 mice were captured with a 30MHz ultrasound transducer. Baseline (B) data were acquired prior to myocardial infarction (MI) induced by a 1-hr occlusion of the LAD followed by reperfusion. Thereafter, cines were acquired at 2, 4, 7, 14 and 28 days post-MI. Displacements were quantified using speckle tracking on the LA cines. DI was determined using Fourier analysis of radial displacement distributed along the endocardial wall, and is the square root of the ratio of the zero-order power term to the sum of zero-order and a scaled first order power terms.

Results:
In Fig. 1, DI is compared to RURE at B and at 5 time-points post-MI. DI values at B are consistently close to 1 (0.96±0.01), and decrease significantly early after MI due to dyskinesia, reaching a minimum at D4 (0.64±0.08). After the first week, motion in the infarct zone becomes more akinetic due to scar formation and DI values partially recover to a plateau late after MI. ANOVA reveals significant differences between B and all post-MI time-points (p < 0.05). In contrast, RURE is less sensitive to dyskinesia at D4 and post-MI estimates are only significant from B for after D4 (p < 0.05).

Conclusion:
Strain-based measures of dyssynchrony are error-susceptible without proper filtering of displacement data. DI has been shown to work well in ultrasound B-mode images, where image artifacts can degrade displacement data.
Abstract 18775: Low Levels of Omega-3s In Hispanics Due to Genetic and Dietary Factors Can be Significantly Improved with a Highly Bioavailable Omega-3 Free-fatty Acid Formulation
Authors: Davidson Michael , Superko Robert , Sninsky John , Ross David , Ferber Sandra , Johnson Judith , Kling Douglas
Published: April 2024

Background:
Hispanic Americans have low fish consumption compared to non-Hispanics. In addition to dietary intake, LC-PUFA plasma levels are affected by FADS1 gene polymorphisms. FADS1 genes code for desaturases that convert MC-PUFAs (linoleic, alpha-linoleic acid) to LC-PUFAs (arachidonic acid (AA), eicosapentaenoic acid (EPA)). The single nucleotide polymorphism (SNP),
rs174546
in the FADS1 gene has previously been shown to be associated with variations in plasma EPA and AA and triglycerides levels . The present study evaluated the prevalence of the
rs174546
SNP genotypes (CC, CT, TT) and corresponding plasma EPA, DHA and AA levels after treatment with an omega-3 free-fatty acid (FFA) formulation in a population of healthy Hispanic volunteers.

Methods:
Forty six Hispanic participants in a statin pharmacokinetic study received 40 mg of simvastatin with and without a 4g daily dose of omega-3 FFA (primarily EPA and DHA ) for two weeks in a cross over study. Plasma samples were collected prior to and at the end-of-treatment in the omega-3 FFA arm for analysis of EPA, DHA, and AA.

Results:
Prior to treatment the Hispanic population had a higher prevalence of TT homozygotes (41%) compared to CC homozygotes (24%) corresponding to significantly different levels of EPA (CC=18 ug/mL; CT=11 ug/mL; TT=7 ug/mL, p <0.0001) and AA (CC=266 ug/mL; CT=202 ug/mL; TT=167 ug/mL, p <0.0001) across genotypes. In response to Omega-3 FFA therapy a substantial increase in EPA was observed, with the largest percent increase in the TT genotype (TT:1054%, CT:573%, CC:253%, p<0.0001). Baseline plasma DHA levels were low suggesting comparable dietary fish intake and changes were similar across genotypes (CC:39%, CT:55%, TT:67%, p=0.2134).

Conclusion:
In contrast to other ethnicities, the T allele in FADS1 polymorphism,
rs174546
is the major allele in Hispanics and the TT genotype is associated with low levels of EPA. This difference in LC-PUFA levels can be exacerbated with low dietary omega-3 intake and may explain the high prevalence of hypertriglyceridemia in Hispanics. Our data suggests that treatment with a highly bioavailable omega-3 FFA may result in significant improvement in omega-3 levels in the Hispanic population.
Abstract 18793: Impact of Chronic Kidney Disease on Outcomes in Patients Undergoing Balloon Aortic Valvuloplasty: Results from the BRAVO Study
Authors: Vlachojannis Georgios , Kini Annapoorna , Mehran Roxana , Gukathasan Nilusha , Cohen Mauricio , Yu Jennifer , Sergie Ziad , Baber Usman , Sartori Samantha , Pyo Robert , Theodoropoulos Kleanthis , Thapi Roja , Roy Swathi , Sayeneni Swapna , Pinnelas Rebecca , Jacobs Evan , Knopf David , Kovacic Jason , Vadde Raj , O'Neill Brian , Sharma Samin K , Dangas George D
Published: April 2024

Background
Balloon aortic valvuloplasty (BAV) is a palliative treatment for severe aortic stenosis that is increasingly performed as a bridge to transcatheter aortic valve replacement. While chronic kidney disease (CKD) is a frequent comorbidity in elderly patients with aortic stenosis undergoing BAV, its impact on in-hospital outcomes has not yet been determined.

Methods
We conducted a retrospective analysis of 421 consecutive patients who underwent non-emergent BAV at two high-volume centers. We analyzed baseline and procedural characteristics as well as in-hospital outcomes according to the presence or absence of CKD, defined as a glomerular filtration rate of <60 mL/min/1.73m
2
. All adverse events were adjudicated by a blinded, independent clinical events committee.

Results
Of the 421 patients who underwent BAV, 251 (59.2%) had CKD. Patients with CKD had significantly higher rates of mortality (8.0% vs. 2.4%, p=0.02) and major bleeding (14.3% vs. 7.6%, p=0.04) as well as net adverse clinical events (18.7% vs. 11.2%, p=0.04) compared to patients without CKD. A secondary analysis stratifying the groups by type of antithrombotic used revealed an almost 3-fold decrease in major bleeding events in CKD patients treated with bivalirudin compared to those receiving heparin (5.8% vs. 14.9%, p=0.01). After multivariate analysis controlling for multiple confounders, CKD remained associated with an increased risk for bleeding (OR 1.99; 95%CI [0.83, 4.78]; p=0.12) and death (OR 2.12; 95%CI [0.61, 7.33]; p=0.24), without statistical significance.

Conclusions
CKD is associated with an increased risk of in-hospital mortality and bleeding complications post-BAV. Further research is warranted to determine whether adverse outcomes in CKD patients can be reduced through selective use of novel devices or alternative pharmacological approaches.
Abstract 18811: Plasma Renin Activity Test Versus US Joint National Committee Guidelines for Selecting Initial Antihypertensive Drug
Authors: Alderman Michael H , Laragh John H , Sealey Jean E , Cohen Hillel W
Published: April 2024

Background:
US National Guidelines promote initiating treatment for nearly all hypertensive patients with a natriuretic drug. We now report a double-blind, randomized controlled trial to compare that with a Plasma Renin Activity (PRA) test guided therapeutic approach.

Methods:
Hypertensive participants (n=164) consented to (i) replacement of antihypertensive drugs with placebo for at least 4 weeks and then (ii) a 5 month double blind study to compare BP control and BP change achieved by initial monotherapy: Experimental = guided by PRA (n=82) v. Control = hydrochlorothiazide (HCTZ) (n=82).

Results:
Eligible subjects were 45% males with a mean±SD age 60±9, entry BP 152±10/86±10mmHg,and median (IQR) PRA 0.7 (0.2, 1.4)ng/mL/hr. Experimental subjects were given a diuretic if PRA <0.65 (n=32?), or olmesartan if PRA ≥0.65 ng/mL/hr (n=50?). At 4 months, 72% of both Experimental and Control groups achieved BP <140/90mmHg, (132±15/76±11 v. 134±14/79±9mmHg,p=.39/.18 respectively). As expected, in subjects with PRA<0.65ng/mL/hr BP decline was similar in Experimental and Control groups. By contrast, in 91 patients with PRA ≥ .65ng/mL/hr, after adjusting for entry BP Experimental subjects (n=50) had a significantly greater mean±SE fall in systolic BP [_-4.9±2.4mmHg (p=.04)] and a borderline significantly greater fall when not adjusted (_-4.5±2.3mmHg, p=.06).

Conclusions:
Effectiveness of PRA guided therapy is identical to US National Guidelines for patients with PRA < 0.65 ng/mL/hr. However, it significantly improved BP treatment in patients with PRA ≥ 0.65ng/ml/hr. Moreover, in this clinical trial of moderately hypertensive patients, initial monotherapy lowered BP to <140/90 mmHg in nearly 3/4 of subjects. These results suggest that routine PRA determination can improve both the effectiveness and efficiency of hypertension treatment.
Abstract 18819: Multi-Center, First-In-Man Evaluation of the Myolimus-Eluting Bioresorbable Coronary Scaffold: 6-Month Clinical and Imaging Results
Authors: Verheye Stefan , webster mark , Stewart Jim , Abizaid Alexandre , Costa Ricardo , Costa J. Ribamar , Yan John , Bhat Vinayak , Morrison Lynn , toyloy sara , Ormiston John
Published: April 2024

Aims:
To evaluate the clinical safety and effectiveness of the DESolve™ Myolimus-Eluting Bioresorbable Coronary Scaffold (DESolve) in patients with single de novo native coronary artery lesions through clinical endpoints and multiple imaging modalities.

Methods and Results:
Background: The DESolve Bioresorbable Scaffold is a novel drug eluting device that combines a PLLA-based scaffold coated with a bioresorbable polylactide-based polymer and the drug Myolimus. Myolimus, a macrocyclic lactone mTOR inhibitor has demonstrated potent anti-proliferative properties in two First-in-Man (FIM) trials using Elixir’s metallic Myolimus-eluting coronary stents. The drug dose is 3 mcg per mm of scaffold length; the same dose as used as in the FIM studies. Sixteen patients with single, de novo coronary artery lesions were enrolled in this prospective, multi-center, single-arm FIM study. One patient did not receive a study stent and was deregistered. The 15 remaining patients are being analysed for multiple clinical endpoints: Device and Procedure Success; Major Adverse Cardiac Events (MACE), a composite endpoint of cardiac death, target vessel MI, and clinically-indicated target lesion revascularization (CI-TLR); clinically-indicated Target Lesion and Target Vessel Revascularization, (CI-TVR) and stent thrombosis assessed at 1, 6 and 12 months and annually to 5 years. Multiple assessments by angiographic, IVUS and OCT at 6 months were completed. An additional analysis using multislice computed tomography (MSCT) will be completed at 12 and 24 months. At 6 months, the in-scaffold late lumen loss was 0.19 ± 0.19 by QCA, the % volume obstruction was 7.18 ± 3.37 by IVUS, and by OCT 98.68 ± 2.44% of struts were demonstrated as covered. There was one MACE, event, a TLR, during the follow-up period. Detailed clinical and imaging results through 6 months will be presented.

Conclusion:
The DESolve™ Myolimus-Eluting Bioresorbable Coronary Scaffold demonstrated both excellent safety and effectiveness in this FIM study, thus warranting further clinical evaluation of the novel technology in larger clinical studies. Detailed clinical and imaging results through 6 months will be presented.
Abstract 18898: Characterization of Proendothelin-1 Derived Peptides Identifies a Co-secreted Modulator of ET-1 Vasoconstriction, and Provides Insights for Biomarker Measurements
Authors: Yuzugulen Jale , Wood Elizabeth G , Douthwaite Julie A , Villar Inmaculada C , Patel Nimesh S , Jegard James , Montoya Alexander , Cutillas Pedro , Hartley Oliver , Ahluwalia Amrita , Corder Roger
Published: April 2024

Background:
ET-1 is strongly implicated in cardiac and renal pathologies both as a potent vasoconstrictor, and as an inducer of tissue remodeling and fibrosis. However, in experimental and human studies ET antagonists are often ineffective. ET-1 biosynthesis occurs via a 212 amino acid peptide preproendothelin-1 (ppET-1); hence other peptides from this precursor may contribute to the biological effects of EDN1 gene expression.

Methods:
Specific immunoassays were used to identify the peptide products of ppET-1 in conditioned media samples from EA.hy 926 and A549 cell lines. Secretion of proET-1 peptides was also investigated using primary cultures of human aortic endothelial (HAEC) and smooth muscle cells (HAVSMC), and cardiomyocytes (HCM). Synthetic proET-1 peptides were used to study their rate of clearance from the circulation in anaesthetized rats, and effects on ET-1 induced vasoconstrictor and blood pressure responses.

Results:
Using specific antibodies 3 peptides were identified: NT-proET-1 (ppET-1[18-50]), MP-proET-1 (ppET-1[93-166]) and CT-proET-1 (ppET-1[169-212]). Specific sandwich ELISAs for these three peptides showed that they were secreted from all cell types studied with levels of release correlating with ET-1. Arterial blood measurements after i.v. administration (1 nmol/kg) of peptide showed markedly different elimination rates. NT-proET-1 had the most rapid clearance (<5 min) and CT-proET-1 the slowest (8% of initial values 40 min after injection). On rat mesenteric resistance arteries MP-proET-1 alone showed no significant vasoconstrictor effect up to 10 nM, but after pre-treatment with ET-1 (1 - 3 nM) it produced a concentration dependent vasoconstriction. Pre-incubation of rat mesenteric resistance arteries with 10 nM MP-proET-1 increased the response of 1 nM ET-1 by 5 fold (P <0.002). MP-proET-1 alone (3 nmol/kg) had no effect on blood pressure in anaesthetised rats, but it significantly increased the duration of the pressor response to ET-1 (0.3 nmol/kg, P <0.02).

Conclusions:
ProET-1 derived peptides may play an important role in vascular pathologies by modulating ET-1 responses, or the actions of other mediators. The slower systemic clearance of CT-proET-1 favors its use as a biomarker of EDN1-linked pathologies.
Abstract 18909: Symptoms and Coronary Anatomy are Associated with Management Decisions in Children and Young Adults with Anomalous Aortic Origin of a Coronary Artery: A Congenital Heart Surgeons' Society (CHSS) Study
Authors: Poynter Jeffrey A , Jacobs Marshall L , Williams William G , Brothers Julie A ,   The Congenital Heart Surgeons' Society Anomalous Aortic Origin of a Coronary Artery Working Group
Published: April 2024

Background:
Anomalous Aortic Origin of a Coronary Artery (AAOCA) is a rare congenital heart lesion associated with myocardial ischemia and sudden death in the young. Evidence-based criteria for managing young patients with AAOCA are lacking. The CHSS began multi-center enrollment of patients with AAOCA age ≤ 30 years to develop these criteria. We hypothesized that demographics, symptoms and features of coronary morphology would correlate with whether or not the patient had surgery.

Methods:
To date, we have enrolled 199 patients from 23 CHSS member institutions (median age at diagnosis= 10.4 years; 64% male). Data was extracted from clinical records. Fifty-three percent were symptomatic at presentation (most commonly chest pain, N=78). AAOCA was diagnosed at autopsy in two patients who presented after sudden death (1 with anomalous left coronary artery [ALCA]; 1 with a single ostium above a commissure). Correlation analysis compared demographics, symptoms, coronary anatomy and management.

Results:
Imaging reports documented anomalous right coronary artery [ARCA] in 142 patients (74%) and ALCA in 51 patients (26%). Surgery was performed in 106 patients (70 ARCA [66%]; 34 ALCA [32%]; 2 ARCA/ALCA [2%]) at a median age of 12.6 years. Overall, 71% of patients with ARCA vs. 51% with ALCA had surgery. Most surgical patients (96/106) had an intramural anomalous coronary artery (69/72 ARCA; 27/36 ALCA). The correlation of diagnostic reports (N=100) with surgical findings was poor (45%). Surgery correlated with symptoms, older age and intramural ALCA (Table).

Conclusions:
A high index of suspicion for coronary anomalies should be present when a young patient presents with exertional chest pain, presyncope or syncope. Surgical management of these patients is influenced by patient symptoms and coronary morphology. Future analysis of this expanding cohort will lead to evidence-based protocols to manage the spectrum of risk in this heterogeneous population of young patients.
Abstract 18927: Geographic Variation of AHA's ‰Life's Simple Seven in Women
Authors: Johnson Caitlin , Rodriguez Fatima , Wang Yun , Foody JoAnne
Published: April 2024

Background:
Evidence shows that individuals achieving AHA’s “Life’s Simple 7” cardiovascular health metrics have significantly reduced risk of CVD incidence and mortality. Geographic variation in CVD risk factors has been previously described. We sought to determine whether CV risk as defined by optimal CV health metrics varied geographically among women.

Methods:
In 2009, Sister to Sister provided free cardiovascular screenings to 9,442 women in 12 cities, including Atlanta, Baltimore, Boston, Chicago, Dallas, Detroit, Jacksonville, Los Angeles, Miami, St. Louis, Tampa, and Washington, DC. Using biometric data collected from screenings supplemented by surveys on CVD risk, we analyzed variance in the “Simple 7” cardiovascular metrics by city. These metrics were defined as being physically active, having normal blood pressure, weight and blood glucose and total cholesterol levels, and eating a healthy diet. We used 6 of these 7 metrics, excluding diet, to assign each city with a risk score.

Results:
Few cities were at optimal health. On average, cities achieved 3.8 out of 6 cardiovascular metrics. From a regional perspective, Atlanta, Dallas and Detroit were significantly lower, and Boston and St. Louis were significantly higher than the city-wide average (see figure 1).

Conclusion:
Significant geographic variation exists in proportion of individuals achieving “ideal CV health” as measured by the AHA’s “Life’s Simple 7”. Given this, solutions to improve community based CV risk will need to be tailored by region.
Abstract 18958: Changes in Wnt-Frizzled System in Heart Failure and Associated AF Substrate
Authors: Dawson Kristin , Qi XiaoYan , Nattel Stanley
Published: April 2024

Introduction:
The wnt-frizzled (Fzd) signaling cascade, important in development, has recently been implicated in post myocardial infarction scar formation. Fzd receptors (Fzd1-6) interact with wnt ligands to produce downstream effects antagonized by the endogenous antagonist sFRP. This study examined the potential role of wnt-Fzd signaling in heart failure (HF), in which atrial-selective extracellular matrix (ECM) remodeling creates a substrate for AF.

Methods:
HF was induced by ventricular tachypacing (VTP 240 bpm) in dogs. Time-dependent changes were studied with VTP ×12 hr, 24 hr, 1 wk or 2 wks. mRNA was measured in freshly isolated left atrial (LA) and ventricular (LV) fibroblasts (qPCR).

Results:
Fzd1 expression was LA selective (16.6 × LV*, P<0.05) but did not change with VTP. Fzd2 increased in LA at 1 wk (15 fold***, ***P<0.001) and 2 wks (13 fold***), increasing less in LV (3.7 fold* at 2 wk). Fzd3 and Fz5 did not change. Fzd4 decreased quickly in LA (12 hr, -5.3 fold**, **P<0.01; 24 hr, -7.6 fold**) and then returned to control. Fzd6 increased slightly in LA at 2 wk (2.9 fold*). Agonists of the pathway, wnt3a and wnt5b, were also investigated. Wnt3a was undetectable in LA or LV fibroblasts. Wnt5b decreased in LA at 12 hr (-4.3 fold**) and 24 hr (-4.25 fold**). LV wnt5b expression decreased later and to a lesser extent: 24 hr (-1.72 fold*) and 1 wk (-1.75*). The endogenous antagonist sFRP1 was expressed selectively in LA (5.5 × LV*). LA levels fell early (-4.8 fold at 12 hr VTP**), remained decreased at 1 wk (-2.2 fold*) and returned to control at 2 wk. Treatment of LA fibroblasts with recombinant sFRP1 (2.5 µg/mL) decreased fibronectin expression (-2.4 fold***), suggesting that sFRP interaction with endogenous wnt-Fzd signaling negatively regulates fibronectin, an important ECM and fibroblast interaction regulator. Fibronectin was upregulated in VTP, with significant changes noted at 24 hrs. Collagen1-α1 was unaffected by sFRP1.

Conclusions:
The wnt-Fzd system is altered in HF, with the most prominent changes occurring in LA, consistent with LA-selective ECM remodeling. Downregulation of sFRP1 may contribute to rapid increases in LA fibronectin expression with VTP/HF, thereby playing an important pathophysiological role in AF-promoting ECM remodeling.
Abstract 18959: Minimally Invasive CABG: Results to 6 years
Authors: McGinn Joseph T , Shariff Masood , Lapierre Harry , Sohmer Benjamin , Goyal Nikhil , Ruel Marc
Published: April 2024

OBJECTIVE:
To evaluate the longitudinal outcomes of minimally invasive CABG (MICS CABG).

METHODS:
We prospectively followed 800 consecutive patients who underwent MICS CABG, performed through a 4-6 cm thoracotomy in the left 5th intercostal space. During MICS CABG, the left internal thoracic artery was harvested under direct vision with long instruments, proximal anastomoses were handsewn onto the ascending aorta after mobilizing it in a stepwise fashion, and all myocardial territories were accessed for distal anastomoses by using an apical positioner and/or epicardial stabilizer. All operations were performed by either one of two surgeons. Mean follow-up was 2.2 years (maximum 6.4 years).

RESULTS:
Mean patient age was 63.5 ± 10.8 years and 197 patients were female (24.6%). A mean of 2.2 ± 0.8 grafts were performed. Peripheral cardiopulmonary bypass assistance was used in 77 patients (9.6%). There were 25 (3.1%) conversions to sternotomy, and 26 (2.7%) reoperations for bleeding. New onset atrial fibrillation occurred in 187 (23.4%). Overall, the median hospital length of stay was 4 days, and perioperative mortality was 1.0% (8/800). No deep wound infection occurred. At 2 years postoperatively, mid-term survival after MICS CABG was 98.0 ± 0.7%, and 22 patients (2.8%) had undergone percutaneous coronary reintervention.

CONCLUSIONS:
These results indicate that MICS CABG constitutes a feasible and increasingly established minimally invasive alternative for patients in need of multivessel CABG. It is associated with a short hospital length of stay, no deep wound infections, and is a safe, reproducible operation yielding survival and durability results in par with that of conventional CABG.
Abstract 18978: Resting Pressure Gradient (iFG) Instantaneous Wave-free ratio (iFR) for Non-culprit Stenosis Evaluation in Patients with Acute Coronary Syndromes. Preliminary Data from the FORECAST Study
Authors: Indolfi Ciro , Polimeni Alberto , Mongiardo Annalisa , Spaccarotella Carmen , Sorrentino Sabato , Curcio Antonio , Caiazzo Gianluca , Torella Daniele , De Rosa Salvatore
Published: April 2024

Background:
The assessment of non-culprit stenoses is an important issue in ACS. Adenosine administration is currently required for functional evaluation of stenosis severity using the fractional flow reserve (FFR). An alternative adenosine-independent index of coronary stenosis, the instantaneous wave-free ratio (iFR), was recently introduced.

Objective:
Aim of the present study was to evaluate the trans-stenotic instantaneous wave-free pressure gradient (iFG), the instantaneous wave-free ratio (iFR) and the fractional flow reserve (FFR) in ACS patients.

Methods:
Intracoronary diastolic pressure was measured proximal and distal to the stenosis during the wave-free period with a pressure wire (Certus, St. Jude, USA) at baseline and upon iv adenosine administration (140 ug/kg/min). The data were acquired with a PowerLab (AD Instruments, USA) and analyzed with a LabChart 7.

Results:
A total of 71 stenoses were evaluated in the present study. iFR showed a correlation with FFR (r=0.61, p<0.001), while a proportional error was documented with the Bland-Altman analysis. At multivariate analysis, the localization of the evaluated stenosis within the coronary tree influenced the correlation of iFR with FFR (p=0.03). ROC analysis showed a promising diagnostic efficiency for detection of significant coronary stenosis with iFR (AUC=0.936; p<0.001) or iFG (AUC=0.944; p<0.001).

Conclusions:
The instant wave-free ratio (iFR) and the resting distal-to-proximal pressure gradient measured during the wave-free period (iFG) showed a good diagnostic performance for the assessment of non-culprit lesions in ACS, representing a promising and adenosine-independent alternative to standard fractional flow reserve (FFR).
Abstract 18990: Impact of Cavotricuspid Isthmus Dependent Right Atrial Flutter Ablation on the Incidence and Recurrence of Atrial Fibrillation
Authors: Reddy Madhu , Janga Pramod , Pamulapati Hema , Bommana Sudharani , Kretsinger Hallie , Reddy Chanakyaram , Barnds Brandon , Reddy Namratha , Atkins Donita , Lakkireddy Dhanunjaya
Published: April 2024

Background:
There is limited data evaluating the impact of cavotricuspid isthmus ablation for right Atrial Flutter (AFL) on the a) development of Atrial Fibrillation (AF) in those without AF and b) recurrence of AF in patients with previous AF.

Methods:
We studied all consecutive patients (with or without previous AF) undergoing cavotricuspid isthmus ablation for symptomatic drug resistant AFL in a large academic center.

Results:
302 patients underwent AFL ablation between 2007 and 2011. Mean age was 65 yrs with 71% males. Mean left ventricular ejection fraction was 51±14%. Median duration since diagnosis of AFL was 2 months (IQ range 1-10) months. 136 (45%) patients had a history of AF (paroxysmal in 95%) and the remaining 166 (55%) patients did not have AF. Patients “with AF” were more likely to be females, have a previous stroke, had higher CHADS2 score, larger left atria and used more antiarrhythmics prior to ablation. 33 (25%) patients “with AF” had AF in the lab spontaneously, by programmed stimulation or with isoproterenol infusion when compared to 11(7%) patients “without AF”; p<0.001. After a mean follow-up time of 24 months, 95 (31%) patients were on antiarrhythmics (46% vs 19% in patients with and without AF respectively). During follow up, 75 (55%) of the patients “with AF”, had a recurrence of AF and 36 (22%) patients “without AF” group developed AF; p<0.001. The predictors of AF during follow up were female gender (p=0.03), number of antiarrhythmics used (p=0.009) and AF induction during the procedure (p<0.001). AF induction during the procedure predicted AF recurrence in patients “with AF” (p=0.020) but not in patients “without AF” (p=0.243).

Conclusions:
At 2 years after AFL ablation a) 22% of the patients with isolated AFL develop AF and b) 45% of the patients with previous AF did not have AF recurrence. AF induction during the procedure predicts recurrence of AF after AFL ablation.
Abstract 18994: Independent and Combined Effect of Heart Failure and Renal Dysfunction on One-year Mortality in Patients with Acute Myocardial Infarction
Authors: Nakatani Daisaku , Sakata Yasuhiko , Suna Shinichiro , Usami Masaya , Usami Masaya , Matsumoto Sen , Hara Masahiko , Hamasaki Toshimitsu , Yasumura Yoshio , Ueda Yasunori , Sato Hiroshi , Hori Msatsugu , Nanto Shinsuke , Komuro Issei
Published: April 2024

Background:
A concept of cardio-renal syndrome has been proposed in clinical practice setting. Little is known whether there exist independent and combined effect of heart failure (HF) and renal dysfunction (RD) in patients with acute myocardial infarction (AMI) in the contemporary era.

Methods:
A total of 4,700 patients with AMI who were registered to the Osaka Acute Coronary Insufficiency Study (OACIS) were studied. Patients were divided based on Killip classification (I, II, III and IV) and estimated glomerular filtration rate (eGFR) with 4 categories (CKD 1,2,3 and 4/5) on admission. One-year mortality rate and risk were compared using log-rank test and Cox regression hazard model.

Results:
Ninety-one % of patients received reperfusion therapy. There was a linear relationship between both HF (3.7%, 15.2%, 32.7% and 43.0% for Killip I, II, III and IV, P<0.001) and RD (1.2%, 3.4%, 13.6% and 32.5% for CKD 1,2,3 and 4/5, P<0.001) with 1-year mortality rate, respectively. Patients with both Killip IV and CKD4/5 had highest mortality rate of 57.6% and risk with a 27-fold higher compared to those with Killip I and CKD 1 (P<0.001) (shown in figures).

Conclusions:
In the contemporary reperfusion era, there exists independent and combined effect of HF and RD on 1-year mortality in patients with AMI. Explorations of novel adjunctive strategies to reduce mortality will be needed for AMI complicated with each or both HF and RD.
Abstract 190: Cardiopulmonary Resuscitation with Rescue Breathing Is Superior to Hands-Only Cardiopulmonary Resuscitation for Children and Infants: Results of a Systematic Review
Authors: Bradley Richard N ,   American Red Cross Scientific Advisory Council
Published: April 2024

Introduction:
Evidence supports teaching hands-only CPR for the initial treatment of cardiac arrest in adults. Unlike adults, however, children and infants with cardiac arrest are more likely to have non-cardiac causes.

Hypothesis:
The objective of this project was to conduct a structured literature review to answer the question, “In children and infants with cardiac arrest treated in an out-of-hospital setting, does compression-only CPR, alone or with supplemental oxygen, compared to CPR with rescue breathing lead to improved outcomes?”

Methods:
We performed a MEDLINE search (“compression only”[Title/Abstract]) AND cardiopulmonary resuscitation[MeSH Terms] with limits children (ages 0 -18). We also performed a search in the Cochrane database for systematic reviews, the Central Register of Controlled Trials, and EMBASE using similar search terms. We also searched applicable bibliographies and used the ‘Cited By’ function in Google Scholar. The study included papers if they evaluated the difference between compression only CPR and CPR with rescue breathing in infants or children. Papers that reported results from studies that used procedures that were beyond the basic life support level were excluded. Each paper was evaluated using specific criteria to determine the level of evidence.

Results:
Sixty-nine records were identified and screened. Fifty-four of these did not meet inclusion/exclusion criteria, leaving fifteen full-text articles that we assessed for eligibility. Eleven of these did not meet inclusion/exclusion criteria, leaving four that we included in the qualitative synthesis. Of these, one good quality study with level of evidence (LOE) 2a and 3 other studies (LOE 4) all opposed the hypothesis. There is a relative paucity of published data on this subject. The majority of the papers published describe evidence from animal models.

Conclusions
: In conclusion, rescuers should provide chest compressions with rescue breathing to children and infants in cardiac arrest; rescuers unwilling or unable to provide compressions with rescue breathing may provide chest compressions alone for these patients.