bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9556: Effect of High Intensity Interval Training in Heart Transplant Recipients - A Randomized Controlled Trial
Authors: Nytrøen Kari , Rustad Lene Annette , Aukrust Pål , Ueland Thor , Hallén Jostein , Holm Inger , Rolid Katrine , Lekva Tove , Fiane Arnt , Amlie Jan P , Aakhus Svend , Gullestad Lars
Published: April 2024

BACKGROUND
High intensity interval training (HIIT) is an efficient form of exercise training in patients with coronary heart disease and heart failure, while heart transplant (HTx) recipients, mainly because of denervation, traditionally have not been exposed to HIIT. Even if many studies have documented effect of exercise in HTx recipients, VO
2peak
remain below normal: 50 to 70% of predicted. Our hypothesis was that HIIT is an applicable and safe form of exercise in heart transplant (HTx) recipients, and that it would markedly improve VO
2peak.
Secondarily, we wanted to evaluate central and peripheral mechanisms behind a potential VO
2peak
increase.

METHODS
Forty-eight clinically stable HTx recipients >18 years old and 1-8 years after HTx underwent maximal exercise testing on a treadmill, muscle strength testing, echocardiography and quality of life questionnaires. They were randomized to either exercise group (a one-year HIIT-program) or control group (usual care).

RESULTS
The mean±SD age was 51±16 years, 71% were male and time since HTx was 4.1±2.2 years. The mean VO
2peak
difference between groups at follow-up was 3.6 [2.0, 5.2] mL/kg/min (
p<
0.001). The exercise group had achieved 89.0±17.5% of predicted VO
2peak
vs. 82.5±20.0% in the control group (
p<
0.001). In addition, the exercise group improved their muscular exercise capacity significantly (
p<
0.001) and had subjectively significant better general health (
p<
0.001). There were no changes in cardiac function measured by echocardiography.

CONCLUSIONS
The present study documents that a long-term, partly supervised and community-based HIIT-program is an applicable, effective and safe way to improve VO
2peak
, muscular exercise capacity and quality of life in HTx recipients. The results indicate that HIIT should be more frequently used among stable HTx recipients in the future.
Abstract 9576: A Nuclear Receptor-microRNA Circuit Links Control of Muscle Fiber Type to Energy Metabolism
Authors: Gan Zhenji , Rumsey John , Hazen Bethany C , Lai Ling , Leone Teresa C , Vega Richard B , Auwerx Johan , Olson Eric N , Kralli Anastasia , Kelly Daniel P
Published: April 2024

Muscle fitness deteriorates in many chronic diseases including heart failure. The mechanisms involved in the coordinate control of the energy metabolic and structural programs that determine muscle fitness are unknown. Recent studies indicate that the nuclear receptors PPARβ (δ) and PPARα exert opposing actions upon muscle endurance in transgenic mice (MCK-PPAR mice). We took advantage of the divergent effects of PPARβ and PPARα in muscle to delineate the regulatory circuitry that orchestrates control of muscle fiber type and energy metabolic programs. Muscle fiber typing and transcriptional profiling revealed that type I fibers were induced in MCK-PPARβ soleus muscle but markedly suppressed in MCK-PPARα muscle. Conversely, type I fibers were significantly increased in PPARα null gastrocnemius muscle whereas shRNA-mediated “knockdown” (KD) of PPARβ in primary skeletal myotubes reduced type I gene markers. Muscle microRNA (miR) profiling revealed that levels of miR-208b and miR-499 were increased in MCK-PPARβ muscle but dramatically reduced in MCK-PPARα muscle. miR-208b and miR-499, which are embedded in the Myh7 and Myh7b genes, respectively, have been shown to activate slow myofiber gene expression. Combined inhibition of miR-208b and miR-499 abolished the enhancing effects of PPARβ on slow myofiber gene expression in MCK-PPARβ myotubes, while transgenic overexpression of miR-499 in MCK-PPARα muscle prevented the PPARα-mediated repression of the type I fiber program, and reversed the poor exercise performance phenotype of the MCK-PPARα mice. PPARβ was shown to mediate its effects on Myh7/miR-208b and Myh7b/miR-499 expression and type I fiber composition in cooperation with the nuclear receptor ERRγ. Lastly, type I fibers were reduced in muscle-specific ERRβ/γ-deficient muscle together with a profound reduction of miR-499 and miR-208b. Taken together, we have identified a nuclear receptor-miRNA circuit that allows for bi-directional, coordinate, control of muscle slow fiber proportion and energy metabolic capacity. This network shows promise as a target for novel therapeutic approaches aimed at enhancing muscle fitness in conditions that lead to muscle de-training and heart failure.
Abstract 9613: Two-dimensional Strain (2d-strain) Analysis for the Differentiation Between Constrictive Pericarditis and Restrictive Cardiomyopathy
Authors: Butz Thomas , Faber Lothar , Piper Cornelia , Reckefuss Norbert , Plehn Gunnar , Horstkotte Dieter , Trappe Hans-Joachim
Published: April 2024

Introduction:
Two-dimensional strain (2DS) is a novel method to measure strain from standard two-dimensional echocardiographic images. The aim of our study was to characterize global and regional function abnormalities using this technique in patients (pts) with constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM).

Methods:
We studied 90 individuals, 58 consecutive pts with heart failure of either proven pericardial (CP) or myocardial origin (RCM; biopsy proven cardiac amyloidosis), and 32 individuals as contol group. Global longitudinal strain (GLS) and regional peak systolic strain (PSS), as well as global transversal strain (GTS) was assessed by 2DS in the apical four-chamber-view using a dedicated software package (Vivid 7, GE Healthcare). Global radial strain (GRS) and global circumferential strain (GCS) was assessed in the parasternal short axis view. All pts underwent a complete echocardiographic and hemodynamic assessment.

Results:
Out of the 90 individuals (mean age: 57±12 years) 27 had CP, 31RCM, and 32 were controls. The thickness of the interventricular septum (IVSD) was significantly increased in pts with RCM (16±4 mm vs. 8±2 mm, resp. 9±2, p<0.001). Mean GLS was -13.2±4.0% in the CP-group, -9.4±3.4% in the RCM-group (p<0.001), and -20.0±3.7% in the control group. The pts with RCM showed a significant base-to-apex gradient of the longitudinal PSS in the septal and lateral segments (see table). GRS was significantly decreased in RCM in comparison to CP (13.5±8.6 % RCM, 32.2±17.4% CP, 35.4±22.1% control, p<0.001). There was no significant difference of GTS and GCS between the RCM and CP groups

Conclusion:
2DS-analysis of GLS, PPS and GRS proved to be useful as additional echocardiographic tool for the differentiation between pts with RCM and CP. The RCM pts showed a significant base-to-apex-gradient of the PSS in the septal and lateral segments.
Abstract 9675: Restoration of Normal Cardiomyocyte Basal and Beta-Adrenergic Receptor (AR) Subtype Modulation of L-Type Calcium Current in Heart Failure by Chronic Beta
3
-AR Deficiency: Insights into the Underlying Electrophysiological Mechanism
Authors: Zhou Peng , Cheng Heng-Jie , Cheng Che Ping
Published: April 2024

Background.
We have previously shown that heart failure (HF) is associated with upregulation of the cardiac β
3
-adrenergic receptor (AR). Isoproterenol (ISO)-induced HF was prevented in β
3
-AR knockout (β
3
KO) mice. However, the cellular mechanism is unclear. The L-type calcium current (I
Ca,L
) plays a fundamental role in cardiac function and is impaired in HF. No previous studies have examined the influence of β
3
KO on I
Ca,L
in normal or diseased states. We assessed the hypothesis that β
3
KO will prevent HF-induced abnormalities of basal and β-AR subtype-stimulated regulation on I
Ca,L
, thereby preserving normal myocyte function.

Methods.
β
3
KO and wild type (WT) mouse experimental groups received ISO (170 mg/kg sq for 2 days), and β
3
KO and WT

mouse control groups received saline (7/group). After 16 weeks (W) of treatment, we compared the response of myocyte contractile function and I
Ca,L
to β-AR subtype stimulation by random exposure of myocytes to ISO (10
-8
M) or a selective β
1
-, β
2
-, or β
3
-agonist, Norepinephrine (NE, 10
-7
M), Zinterol (ZIN,10
-5
M) and BRL-37,344 (BRL,10
-8
M), respectively, during drug superfusion.

Results.
ISO-treated WT

mice had HF onset at 8W and progressed to severe HF at 16W. Compared with normal myocytes (N), basal I
Ca,L
(HF:4.1 vs N:7.8 pA/pF) and cell contraction (dL/dt
max
, 76 vs 144 µm/s) decreased by more than 40% in HF myocytes. ISO-stimulated I
Ca,L
(14% vs 32%) was attenuated accompanied by a diminished NE-mediated increase in I
Ca,L
(16% vs 37%), but enhanced BRL-induced decreases in I
Ca,L
(17% vs 29%).The response of I
Ca,L
(17% vs 29%) to ZIN was relatively unaltered in HF myocytes. Importantly, in ISO/β
3
KO myocytes, the basal I
Ca,L
(8.1 pA/pF) and dL/dt
max
(154 µm/s) remained close to control

levels with preserved β-stimulated positive modulation on I
Ca,L
. The increases in I
Ca,L
in response to ISO (33%), NE (35%) or ZIN (13%) were similar as that in normal WT myocytes, respectively.

Conclusion.
Chronic β
3
-AR deficiency prevents HF-induced abnormalities of basal and β-AR subtype-stimulated modulation on I
Ca,L
and leads to preservation of myocyte contractile function in a mouse model of progressive HF. These findings provide the first electrophysiological evidence that upregulation of β
3
-AR in HF is detrimental.
Abstract 9753: Highly Electronegative LDL is Elevated in Patients With Acute Myocardial Infarction and Triggers Platelet Activation and Aggregation
Authors: Chan Hua-Chen , Ke Liang-Yin , Chu Chin-Sheng , Lee An-Sheng , Shen Ming-Yi , Cruz Miguel A Cruz , Cheng Kai-Hung , Chan Hsiu-Chuan , Lai Wen-Ter , Yen Jeng-Hsien , Sawamura Tatsuya , Sheu Sheng-Hsiung Sheu , Chen Chu-Huang
Published: April 2024

Background:
Human LDL can be chromatographically resolved into 5 subfractions. L5, the 5th and most negatively charged subfraction, is capable of inducing atherogenic responses in vitro and in vivo. Platelet activation and aggregation are major events underlying acute thrombosis in myocardial infarction (MI). We examined the relationship between L5 and acute MI and the role of L5 in platelet activation and aggregation.

Methods and Results:
Plasma L5 concentration ([L5]) was measured and compared between subjects with (1) no risk factors (healthy controls), (2) STEMI, (3) stable coronary artery disease (CAD), and (4) hyperlipidemia (HLP) without CAD. In STEMI subjects, LDL cholesterol (LDL-C) levels were similar to those in CAD and control subjects and lower than those in HLP subjects, but L5/LDL% and [L5] (L5/LDL% × LDL-C) were significantly elevated (Table). L5 from STEMI subjects but not L1 (least electronegative LDL subfraction) induced tissue factor and P-selectin expression in human coronary arterial endothelial cells (ECs) in a concentration-dependent manner; in platelets, L5 increased glycoprotein (GP)IIb/IIIa and P-selectin expression and decreased cAMP production (for all, n=8,
P
<.01 vs PBS). L5 also increased ADP-stimulated platelet aggregation twofold higher than L1 and induced massive platelet–EC adhesion. Experiments with pharmacologic inhibitors indicated that L5 signals through platelet-activating factor receptor and lectin-like oxidized LDL receptor-1 to reduce cAMP production via Akt and trigger granule release and GPIIb/IIIa activation via PKC-α. Injection of human L5 (5 mg/kg) in C57BL/6 mice twice a week for 6 weeks shortened tail-bleeding time by 43% when compared to L1 (n=3;
P
<.01) and increased expression of P-selectin and GPIIb/IIIa in mouse platelets.

Conclusions:
L5 triggers platelet activation and aggregation, as well as adhesion to ECs. The significant elevation of L5 in STEMI strongly suggests L5’s involvement in acute MI.
Abstract 9883: Atenolol versus Bisoprolol after Acute Myocardial Infarction
Authors: Shin Dong-Ho , Kim Jung-Sun , Kim Byeong-Keuk , Park Sungha , Lee Sang-Hak , Ko Young-Guk , Choi Donghoon , Ahn Hyun-Ah , Joung Sun-Ho , Park Young Mi , Hong Myeong-Ki , Jang Yangsoo
Published: April 2024

Objectives
In the controversies regarding the role of beta-blockers, the key might be how different newer beta-blockers are from atenolol. We sought to compare mortalities between patients with atenolol and bisoprolol at discharge after acute myocardial infarction (AMI).

Methods
Total 15,776 AMI patients admitted in 211 centers via emergency department were registered to the Korean Health Insurance Review & Assessment Service database in 2009. Beta-blockers were used in 11,053 patients (75.6%) at discharge. The final analytic cohort consisted of the patients who received atenolol (564 patients) or bisoprolol (2,139 patients) at discharge (total 2,703 patients). The endpoint was all-cause mortality, and death registration of the government at the middle of July 2010 was used to identify mortality cases. Besides Cox proportional hazard model, propensity score (PS) analysis was used as adjustment, weighting and matching methods.

Results
During 2,372.4 person-years of observation, there were 144 deaths (cumulative incidence 5.7%). Mortality rates were not different between patients with atenolol and bisoprolol (6.1% vs 5.6%, respectively ; p=0.564). In the multivariate and propensity score analyses, however, risk reduction by bisoprolol became larger, especially as much as 44% in PS matched analysis (HR 0.56, 95% CI 0.35 ~ 0.89, p=0.014). (Table & Figure)

Conclusion
Compared to atenolol, bisoprolol might reduce mortality after AMI.
Abstract 9897: Frequency of Non-Systems Delays in STEMI Patients Undergoing Primary PCI and Implications for Door-to-Balloon Time Reporting. A Report from The ACTION Registry®-GWTG™ and AHA
Authors: Cotoni David A , Roe Matthew T , Li Shuang , Vetrovec George W , Kontos Michael C
Published: April 2024

Introduction:
Door to balloon (D2B) time ≤90 minutes (min), and percentage of primary PCI patients (pts) with a D2B ≤90 min are used as performance metrics by many organizations. Pts can be excluded from this measure if they have a non-systems related delay. However, how frequently exclusions occur, and how it affects the reporting of D2B times at the hospital level is unknown.

Methods:
The percentage of pts having non-systems delays (cardiac arrest, intubation, difficult vascular access, etc) for primary PCI at the hospital level was calculated using data from the ACTION Registry®-GWTG™. Pts were excluded if the first ECG was not diagnostic, or were transferred to or from another hospital. Hospitals having < 36 primary PCIs during the study period were also excluded. Hospitals were categorized into three groups based on tertiles of percentage of excluded pts. The percentage of hospitals with a D2B ≤90 min in ≥90% of pts were calculated by first including and then excluding pts that had non-systems delays.

Results:
From 1/1/07-3/31/11, 43,909 pts from 294 hospitals were included. The percentage of exclusions recorded differed substantially among hospitals, ranging from 0-68% of pts (median 9.2% [IQR 5.6%, 13.5%] with low tertile ≤7.1%, intermediate tertile 7.1% to 11.2% and high tertile ≥11.2%. Reasons for exclusion included vascular access difficulty (7.8%) cardiac arrest/intubation (38%) and PCI procedural difficulties (20%). There were no significant differences in hospital annual total MI, STEMI, or primary PCI volumes, or hospital bed size among the three groups. Including pts with non-systems delays significantly increased D2B times and decreased the proportion of pts achieving D2B ≤90 min as well as percentage of hospitals having ≥90% of STEMI pts with D2B ≤90 min (TABLE).

Discussion:
The proportion of pts excluded from D2B reporting varies substantially among hospitals. This has an important impact on reported performance measures.
Abstract 9906: Losartan/hydrochlorothiazide Combination was Superior to High-dose Losartan in Controlling Morning Hypertension and Reducing Urinary Albumin Excretion
Authors: Kai Hisashi , Ueda Tamenobu , Kaneyuki Masashi , Shihara Miwako , Toyama Yasuyuki , Imaizumi Tsutomu
Published: April 2024

Background:
There is little evidence for treatment of morning hypertension, an independent risk for cardiovascular events. Thus, we compared the efficacy of losartan/hydrochlorothiazide combination and high-dose losartan in patients with morning hypertension.

Methods:
A total of 216 outpatients having hypertension medication were enrolled in a 3-month, prospective, randomized, open-labeled, multicenter trial, when they had systolic blood pressure (SBP) greater than 135 mmHg and/or diastolic blood pressure greater than 85 mmHg in the morning on home blood pressure self-measurement. An antihypertensive drug was randomly switched to a 50-mg losartan/12.5-mg hydrochlorothiazide combination tablet (Combination group, N=109) or 100-mg losartan (High-dose group, N=106).

Results:
At baseline, SBP levels, clinical background, and biochemical parameters were similar in the two groups. Primary end-point: Morning SBP was reduced by 18 mmHg in Combination group and by 8 mmHg in High-dose group (p<0.001 for both), whereas the resultant levels were lower in Combination group than in High-dose group (P<0.001). Secondary end-points: Urinary albumin excretion (UAE) was reduced in Combination group (P<0.05), but not in High-dose group, although estimated glomerular filtration rates were not changed in either group. Serum uric acid (UA) was decreased in High-dose group (P<0.001), but was not changed in Combination group. %UAE reduction was significantly associated with %morning SBP reduction, UA reduction (negatively), or combination regimen. Multiple linear regression analysis exhibited that %morning SBP reduction was an independent factor associated with %UAE reduction (β=0.277, P<0.05). After adjustments for treatment regimen and UA reduction, %UAE reduction was positively correlated with the tertiles based on morning SBP reduction levels (P=0.02 for trend).

Conclusions:
Losartan/hydrochlorothiazide combination was more effective than high-dose losartan for controlling morning hypertension and reducing UAE. The reduction in morning SBP was associated with UAE reduction in patients with morning hypertension.
Abstract 18015: Loss of Swi/snf-complex Subunit Heart of Stone Leads to Cardiac Hyperplasia in Zebrafish
Authors: Zimmermann Tobias , Berger Ina , Just Steffen , Rottbauer Wolfgang , Dahme Tillman
Published: April 2024

Fish and also neonatal mice possess the capacity to regenerate their hearts after myocardial damage. The adult mammalian heart only has a very limited capacity to regenerate after cardiac injury. Myocardial regeneration in zebrafish and newborn mice involves the dedifferentiation and proliferation of resident cardiomyocytes to replace the injured tissue. Unfortunately, only little is known about the factors and signaling cascades that regulate this regenerative capacity.

In a forward genetics ENU-screen in zebrafish, we recently isolated the mutant heart of stone (hos). Hearts of hos mutant embryos show a severe thickening of the ventricle with almost complete obliteration of the ventricle. Based on cell count assays using histological sections we find significantly increased cell numbers in hos mutant ventricles. Based on BrdU incorporation assays as well as H3P and PCNA stainings, we find that ventricular hyperplasia in hos is caused by significantly enhanced cardiomyocyte proliferation.

By positional cloning we show a splice donor site mutation within the zebrafish hos gene. hos is a subunit of the SWI/SNF chromatin remodeling complex, which is known to be involved in transcriptional regulation. The identified hos mutation specifically leads to an integration of Intron7 resulting in a reading frame shift and thereby to premature termination of hos protein translation. Injection of wild-type hos mRNA in hos mutant embryos restores the wild-type, while injection of morpholinos directed against the splice donor site of Exon7 phenocopy the hos mutant phenotype. In addition, by generating hos-null zebrafish using morpholinos directed against the translational start site of hos, we are also able to induce ventricular hyperplasia, suggesting that the hos mutation results in the complete loss of hos function. Interestingly, in contrast to hos-deficient embryos, targeted knockdown of the zebrafish SWI/SNF-complex core component BRG1 leads to severe hypoplastic hearts, indicating that hos in zebrafish might play a repressive role on SWI/SNF complex function and the control of cardiomyocyte proliferation in vivo.
Abstract 18032: Increased Late Sodium Current During Early Heart Failure Development Induced by Chronic Sympathetic Activation
Authors: Schoenleitner Patrick , Wakula Paulina , Engelhardt Stefan , Pieske Burkert M , Heinzel Frank R , Antoons Gudrun
Published: April 2024

Chronic sympathetic activation promotes myocardial hypertrophy and heart failure. In mice overexpressing the human β1-adrenoreceptor (β1-OE), cytosolic [Na+]i increases during early stages of cardiac remodeling (8-12 weeks), thereby slowing relaxation and increasing diastolic [Ca2+]i due to increased Na+/Ca2+ exchanger (NCX) reverse mode activity. Here we investigate whether reduced Na+ efflux via Na+/K+ ATPase (NKA) regulation, or enhanced Na+ influx (voltage-dependent Na+ current or TRPC channel regulation) may account for increased [Na+]i in young β1-OE mice.

In β1-OE mice (8-12 weeks) and their wild-type (WT) littermates protein expression of NKA and phospholemman (PLM) was determined by Western blot in ventricular homogenates or isolated ventricular myocytes (TRPC 1, 3, 6) and normalized to GAPDH. NKA current (Ipump, whole cell voltage clamp) was measured as the difference in outward current after rapid solution switch to 0 K+ external solution. The persistent component of the Na+ current, INa,late, was measured as the current sensitive to 30 μm Tetrodotoxin (TTX).

In β1-OE, NKA α1 subunit expression was unchanged, whereas the α2 subunit was reduced (0.87±0.09 in β1-OE, n=5 vs. 1.24±0.08 in WT, n=4; p<0.05; mean±s.e.). Phosphorylated PLM was increased (1.3±0.05 in β1-OE, n=5 vs. 0.748±0.06 in WT, n=4; p<0.001), and total PLM was reduced in β1-OE mice (0.71±0.08 in β1-OE, n=5 vs. 1.23±0.18 in WT, n=4;p<0.05). TRPC 1, 3 and 6 expression was unaltered. Maximal Ipump density (100 mM [Na+]i in the pipette) was unchanged. With 10 mM [Na+]i, Ipump was significantly increased, indicating a higher Na+ affinity of NKA in β1-OE myocytes. INa,late was increased in β1-OE myocytes: at the end of pulse amplitude was -0.149 ± 0.034 pA/pF in β1-OE, n=10 vs. -0.063± 0.018 pA/pF in WT, n=9; p<0.05; integrated current was 138 ± 17 pC/pF in β1-OE, n=10 vs 85 ± 17 pC/pF in WT, n =9; p<0.05.

In conclusion, in β1-OE mice, increased INa,late contributes to elevated [Na+]i during chronic sympathetic activation. Higher Na+ affinity of NKA due to less inhibition by phospholemman only partially compensates increased Na+ influx at this early stage of heart failure development.
Abstract 18071: Integrating Three-Dimensional Imaging for Aortic Valve Stenosis Assessment. A Pilot Multimodality Imaging Study Comparing Classic vs. Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis
Authors: Cavalcante Joao L , Patel Mitika T , Katz William E , Schindler John T , Crock Frederick W , Khandhar Sameer J
Published: April 2024

BACKGROUND:
Assessment of aortic stenosis (AS) severity is critical for treatment decisions but challenging in patients with severe AS (aortic valve area, AVA <1.0 cm2) and low gradients (mean AV gradient <40 mmHg). We sough to evaluate the incremental utility of 3D multidetector computed tomography (MDCT) over TTE for assessment of AS severity in patients with either depressed (classic low-flow, low-gradient, CLFLG, LVEF <50%) or preserved LV systolic function (paradoxical low-flow, low-gradient, PLFLG, LVEF ≥50%) is unknown.

METHODS:
Sixteen patients who underwent TTE, invasive hemodynamics with a right heart catheterization and dual lumen pigtail catheter, and MDCT studies within 30 days were prospectively studied (10 CLFLG and 6 PLFLG). Mean age was 76±10 years with 26% females. TTE parameters included LVEF, systolic LVOT diameter (LVOT-D) and conventional AV Doppler assessment. MDCT evaluated ratio of maximal to minimal LVOT-D (eccentricity index), mean systolic LVOT-D, and AVA by planimetry. Corrected AVA was calculated by substituting the MDCT-derived mean LVOT-D into continuity equation (MDCT-AVA).

RESULTS:
Figure 1 shows hemodynamics and imaging parameters measured. Despite good correlation between TTE-AVA and MDCT-AVA (r=0.85, p<0.0001), AVA was underestimated in 10/16 of patients by either TTE or invasive hemodynamics, irrespective of the baseline LVEF (p < 0.0001 for both). Dimensionless index also correlated better with MDCT-AVA (r=0.71, p=0.002) then with TTE-derived AVA (r=0.58, p=0.003) or by cath-derived AVA (r=0.47, p=0.02).

CONCLUSION:
In patients with severe AS and low-gradients, MDCT imaging revealed eccentric LVOT in most patients, resulting in underestimation of 2D TTE-AVA. Integration of 3D imaging dataset with either 3D-transesophageal echocardiography or MDCT may improve AS severity classification of these challenging patients. Larger cohort studies will be needed to ascertain the impact on treatment decisions.
Abstract 18213: Advanced Glycation End-Product Inhibition With Alagebrium Slows Age-Related Large Vessel Arterial Stiffening in Healthy Elderly Humans
Authors: Shibata Shigeki , Fujimoto Naoki , Hastings Jeffrey L , Bhella Paul S , Carrick-Ranson Graeme , Sarma Tom , Okada Yoshiyuki , Palmer Dean , Boyd Kara , Livingston Sheryl , Levine Benjamin D
Published: April 2024

Background:
Lifelong exercise training maintains youthful compliance of the central arteries, while even prolonged (1 yr) and intense training started later in life failed to reverse age-related central arterial stiffening, possibly because of accumulation of irreversible advanced glycation end-products (AGE). Alagebrium breaks AGE crosslinks and improves central arterial compliance in animals. However, little is known how Alagebrium would affect central arterial compliance in previously sedentary elderly humans. Moreover, it is unclear whether a strategy of exercise training combined with Alagebrium would improve central arterial compliance.

Methods:
Sixty two healthy elderly subjects were randomized into 4 groups: a) Sedentary+placebo; b) Sedentary+Alagebrium (200mg/day); c) Exercise+placebo; and d) Exercise+Alagebrium. Fifty seven/62 subjects (67±6 yrs; 37f/20m) completed 1 yr of intervention followed by repeat measurements. Arterial compliance were evaluated with Modelflow generated aortic age (A-age), central and peripheral pulse wave velocity (PWVs), carotid artery, and ascending and descending aorta beta stiffness indices (Beta indices), and augmentation index (AI). A-age was calculated from the finger blood pressure waveform (BMEYE) and stroke volume (Thermodilution) (
Shibata 2010
). Central blood pressure, PWVs and AI were measured with applantation of tonometry (SphygmoCor). Aortic and carotid arterial geometries were assessed with MRI and ultrasound, respectively.

Results:
A-age increased less over the 1 yr intervention in the Alagebrium groups (Medication х Time effect p=0.066). Also, AI increased significantly less in the Alagebrium groups (Medication х Time effect p=0.034). However, exercise training did not impact on any of these indices. There were no significant differences in either Beta indices or PWVs. No subject developed aortic dilatation or had any CV complications (safety endpoint).

Conclusion:
Breaking of AGE cross links with Alagebrium was safe, and slowed but did not reverse age related large vessel arterial stiffening in elderly humans without an additive effect of exercise training. The absence of concordant changes in all indices suggests that these effects were modest.
Abstract 18234: miR-362-3p Decreases hERG Expression and is Associated With an Unidentified Form of Congenital Long-QT Syndrome
Authors: Shao Minghai , Wei Rongrong , Tisdale James E , Liu Wanqing , Overholser Brian R
Published: April 2024

Introduction:
Endogenous microRNAs (miRs) regulate cardiovascular disease by modulating diverse cellular processes. We recently discovered that miRs may mediate the association between a single nucleotide polymorphism (rs1533317) and QT interval prolongation; identified in a previous genome-wide association study (GWAS). The objective of this research was to assess the ability of the identified miRs to regulate the expression of hERG (i.e. KCNH2).

Methods:
Through a previous genome-wide integrated miR-transcriptome analysis, the expression of 9 miRs were significantly associated with rs1533317 (p< 1x10
-5
). To assess this relationship further, a correlation analyses between transcriptome and miRNome data was performed related to the down-regulation of KCNH2. The potential targeting of KCNH2 by miR was validated using a Dual-Luciferase Assay of the KCNH2 3′-UTR. SK-Br-3 cells were co-transfected with miR mimic or negative control and the KCNH2-3’UTR reporter clone. The reporter plasmid, renilla, was used to control for transfection efficiency. To further assess the ability of miRs to down-regulate KCNH2, SK-Br-3 cells (endogenous KCNH2 expression) were transfected with miR mimic or control and KCNH2 protein expression was assessed by Western blot analysis.

Results:
Out of the 9 assessed, miRs 362-3p, 98, 148, 129*, and 186 were significantly associated with down-regulation of KCNH2 based on the transcriptome and miRNome data (p<0.001). From the Luciferase assay, miR-362-3p was the only miR to significantly reduce KCNH2 3’UTR activity (mean ± SE of 42.6% ± 16.9) relative to control, whereas KCNH2 3’UTR activity was enhanced by miR-98 by an unknown mechanism (figure). Endogenous KCNH2 protein expression was reduced by 33.9% ± 5.3 relative to GAPDH by miR 362-3p (p=0.01).

Conclusion:
Upregulation of miR-362-3p decreases KCNH2 expression and may be the underlying mechanism for a previously reported unidentified form of LQTS regulated by rs1533317.
Abstract 18245: Results of the Chronic Heart Failure Intervention to Improve Medication Adherence (CHIME) Study: A Randomized Self-Management Intervention in High Risk Non-Adherent Patients
Authors: Granger Bradi B , Bosworth Hayden , Hernandez Adrian , Reed Shelby , Ekman Inger
Published: April 2024

Background:
Heart failure (HF) remains a primary cause of avoidable hospitalizations, disability and death. Taking evidenced-based medications is one component of guideline-based self-management, and is associated with improved clinical outcomes. Despite benefits, patients struggle with medication adherence in daily life and adherence remains less than 50%. Interventions to improve medication adherence have been limited in their ability to show an effect over time.

Purpose:
To evaluate the efficacy of a self-management intervention designed to develop person-centered symptom identification and to improve symptom response and medication adherence in high-risk persons with HF.

Methods:
Patients with HF and at high risk for non-adherence (n=84) were randomized to an attention control or the intervention. A prospective, randomized controlled design was used to pilot test the efficacy of an intervention to promote adherence to the medication regimen in high risk patients with chronic heart failure. The intervention was administered at 3 month intervals by a nurse over the phone with a focus on skill-based teaching for symptom recognition and rapid response, medication adherence strategies, and self-management activities. Longitudinal analysis was performed to evaluate the magnitude of change in adherence and symptom-related events at 3, 6 and 12-month clinic visits. Efficacy was measured as improved adherence using the Morisky adherence scale and pill count.

Results:
Patients in the intervention arm were almost four times as likely to be adherent to medications at 12 months as compared to attention control (OR 3.92; 95% C.I. 1.83, 8.40; p= .0006). Symptom recognition; accuracy and timeliness of medication reconciliation; appointment keeping; and caregiver engagement scores were improved in the intervention group. Readmissions and emergency department use were not statistically different.

Conclusions:
A nurse administered self-management intervention that includes a symptom recognition and response plan component improves medication adherence and shows a trend in decreased hospitalizations.
Abstract 18292: Incidence and Recurrence of Atrial Fibrillation in Patients Undergoing Cavotricuspid Isthmus Ablation for Typical Atrial Flutter
Authors: Reddy Madhu Y , Pillai Anand , Vallakati Ajay , Yarlagadda Vivek , Ponnaganti Gopi C , Atkins Donita , Bommana Sudharani , Janga Pramod , Maybrook Ryan , Sridhar Arun , Dawn Buddhadeb , DiBiase Luigi , Natale Andrea , Lakkireddy Dhanunjaya
Published: April 2024

Background:
A proportion of patients with cavotricuspid dependent right atrial flutter (AFL) have previous episodes of atrial fibrillation (AF). Many patients with isolated AFL (no previous AF) develop AF after AFL ablation. There is limited data evaluating the impact of AFL ablation on the a) development of AF in those without AF and b) recurrence of AF in patients with previous AF.

Methods:
We performed a retrospective study including all consecutive patients (with or without previous AF) undergoing cavotricuspid isthmus ablation for AFL in a large academic center.

Results:
A total of 589 patients underwent AFL ablation between 2007 and 2012. Mean age was 64 ±13 years with 74% males. Mean left ventricular ejection fraction was 50 ±14%. Median duration since diagnosis of AFL was 2 months (IQ range 1-10) months. 289 (49%) patients had a history of AF (paroxysmal in 95%) and the remaining 300 (51%) patients did not have AF. Patients “with AF” were on more antiarrhythmics (AADs) prior to ablation when compared to those “without AF”. 67 (23%) patients “with AF” had AF in the lab spontaneously, by programmed stimulation or with isoproterenol infusion when compared to 27 (9%) patients “without AF”; p<0.001. After a mean follow-up time of 31 months, 200 (34%) patients were on AADs (47% vs 12% in patients with and without AF respectively). During follow up, 166 (57%) of the patients “with AF”, had a recurrence of AF and 87 (29%) patients “without AF” developed AF; p<0.001. The independent predictors of AF during follow up in patients with prior AF were CHADS2 score, number of AADs used and AF induction during the procedure. In patients without prior AF, LVEF was the only independent predictor of incident AF

Conclusions:
At 2.5 years after AFL ablation a) 29% of the patients with isolated AFL develop incident AF and b) 43% of the patients with prior AF do not have AF recurrence. LVEF is the only independent predictor for new onset AF in patients without prior AF.
Abstract 18295: Comparison of Long Term Health and Economic Outcomes of ED Triage Strategies for Patients With Acute Chest Pain
Authors: Goehler Alexander , Mayrhofer Thomas , Pursnani Amit , Lumish Heidi , Barth Cordula , Nagurney John T , Truong Quynh A , McMahon Pamela , Gazelle Scott G , Hoffmann Udo
Published: April 2024

Background:
Cardiac CT, functional testing and expedited ED triage with subsequent outpatient testing have been proposed as viable strategies to triage patients presenting with acute chest pain. However, long term health and economic outcomes data are not available.

Methods:
We developed a Markov microsimulation model to examine 4 ED triage strategies: early CCTA (CCTA) and standard ED evaluation (SOC) based on ROMICAT II, a consensus guideline based strategy, and a previously published expedited ED triage protocol using two troponin measurements. As model input parameters, we used demographics, risk factors and resource utilization as observed in the ROMICAT II study. The model predicted the number of diagnostic tests and costs for the initial ED presentation, 5-year mortality and lifetime outcomes and determined the incremental cost-effectiveness ratios (ICER).

Result:
The model accurately predicted multiple ROMICAT II endpoints: Length of stay (CCTA: 23.2 hr (model) vs. 23.2 hr (ROMICAT II trial); SOC: 30.3 hr vs. 30.8 hr), frequency of PCI (CCTA: 5% vs. 5%; SOC: 3% vs. 3%), cumulative radiation exposure (CCTA: 14.0 mSv vs. 14.3 mSv; SOC: 6.1 mSv vs. 5.3 mSv), and total costs during initial ED presentation (CCTA: $4,356 vs. $4,289; SOC: $4,179 vs. $4,060). The expedited ED protocol resulted in substantial savings of resources during the initial ED presentation (Table). After 5 years, however, mortality was highest in the expedited ED strategy and lowest after early CCTA. Moreover, lifetime ICER was $39,700/QALY for CCTA compared to the expedited ED protocol, while SOC and consensus optimal SOC strategies were dominated (i.e., less effective and more expensive).

Conclusion:
A Markov microsimulation analysis based on ROMICAT II outcomes predicts that for long term health and economic outcomes CCTA is a cost-effective ED triage strategy for patients presenting with acute chest pain compared to alternative strategies.
Abstract 18387: Compliance With Chronic Coronary Artery Disease Secondary Prevention Guidelines in the USA
Authors: Lopez-Jimenez Francisco , Zysek Victoria , Roger Veronique , Somers Virend , Liesinger Juliette , Ting Henry , Thomas Randal , Sochor Ondrej
Published: April 2024

Objectives:
To assess compliance with chronic coronary artery disease (CAD) secondary prevention guidelines in the USA, to determine time trends, and to identify potential sociodemographic predictors of low compliance.

Design, Setting and Participants:
We analyzed the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2010, representative of non-institutionalized civilian population in the USA. We included people with self-reported previous diagnosis of CAD, angina or myocardial infarction (MI).

Primary Outcome:
Adherence to secondary prevention guidelines including blood pressure control, lipid control, not smoking, normal body mass index, physical activity at goal, and meeting all 5 outcomes (“all-or-none”). Use of antiplatelet therapy was reported and analyzed from 1999-2004.

Secondary Outcome:
Use of beta-blocker therapy in people with history of MI; in diabetes (DM), use of ACE-inhibitors or angiotensin receptor blocker, and HgbA1C <7%. Age, gender, race, income, education and insurance status were evaluated as covariates. Analyses were weighed according to Center for Disease Control guidelines.

Results:
There were 62,160 individuals in the cycle data of which 2,615 comprised the study group, representative of 73,574,548 individuals in the USA. Mean age was 65 yr, 58% men, 79% white. Only 2.8% of people with CAD met all 5 main outcomes. Only blood pressure and LDL control showed significant improvement over time, see Figure. Antiplatelet therapy was reported in 58.2%. Of those with history of MI, only 50.5% were on a beta-blocker and of those with history of DM, 59.4% were using either an ACE-I or an ARB; and 54% had a HgbA1C less than 7%. When adjusting for demographics, no significant differences were found regarding compliance with all 5 main outcomes.

Conclusions:
Adherence to guidelines for secondary prevention of CAD is suboptimal. There is an immense opportunity for improvement in secondary prevention for CAD in the USA.
Abstract 18460: A Comparison of Complexity of Extraction Between Sprint Fidelis and Other Right Ventricular Leads
Authors: Reddy Madhu Y , Vallakati Ajay , Lipatov Kirill , Janga Pramod , Ponnaganti Gopi C , Yarlagadda Vivek , Bakhtiani Ramchandur , Atkins Donita , Bommana Sudharani , Reddy Namratha , Pimentel Rhea , Emert Martin , Dendi Raghuveer , DiBiase Luigi , Natale Andrea , Dawn Buddhadeb , Lakkireddy Dhanunjaya , Berenbom Loren
Published: April 2024

Introduction:
There is no data comparing the relative difficulty of extraction between Sprint Fidelis and other right ventricular (RV) leads.

Methods:
We performed a retrospective analysis of all consecutive RV lead extractions in a single large referral center performed between 2005 and 2011. RV leads were grouped into Fidelis, non-Fidelis ICD and pacemaker leads. Indications, baseline characteristics, procedural variables and outcomes were compared between the different RV leads.

Results:
A total of 475 patients were included in the study of which Fidelis, non-Fidelis ICD and pacemaker lead was extracted in 198 (42%), 128 (27%) and 149 (31%) of the patients with a mean lead age of 47, 42 and 71months respectively (p=0.002). Mean age of the population was 64years with no difference across the groups. The indications for extraction were prophylaxis (32%), infection (25%) and malfunction (18%) with Fidelis lead much more likely to be extracted for prophylaxis and malfunction than for infection when compared to the other 2 groups (p<0.001). Extraction support (ES) was needed in 302 (64%) (laser in 57% and mechanical device only in 43%) of the leads. Many more leads needed ES in the Fidelis group (77%) when compared to either the non-Fidelis ICD (56%) or the pacemaker group (52%) (p<0.001). Analysis of leads >24months old revealed that for a given lead age, Fidelis lead was much more likely to require ES when compared to both non-Fidelis ICD lead and the pacemaker lead (p=0.001). Complications occurred in 16%, 15% and 6% of the patients with Fidelis, non-Fidelis ICD and pacemaker leads respectively (p = 0.003 between ICD and pacemaker patients). One major complication occurred each in Fidelis and pacemaker group patients.

Conclusion:
Extraction of Sprint Fidelis lead appears to be more difficult than other RV ICD or pacemaker leads with similar major complication rate.
Abstract 18479: New Heart Failure Diagnostic and Prognostic Biomarkers Discovered Using Capillary Electrophoresis Coupled to Mass Spectroscopy
Authors: Berry Matthieu , Galinier Michel , Delmas Clement , Fournier Pauline , Desmoulin Franck , Turkieh Annie , Barutaut Manon , Caubere celine , Mischak Harald , Kalogeropoulos Andrea , Georgiopoulou Vasiliki , Butler Javed , Smih Fatima , Rouet Philippe
Published: April 2024

Blood heart failure (HF) biomarkers such as the natriuretic peptides (NP) are widely used but the NP biomarker family has limitations and HF diagnosis remains too often complicated because of atypical presentations and the need of specialized care access. More specific and accurate biomarkers with detection method allowing for facilitated large scale HF screenings are required. Indeed, 30 % of the patients admitted to emergency care for acute dyspnea have a BNP concentration in a « grey zone » that do not allow for diagnosis. Thus, diagnosis of these patients is costly and time-consuming while a rapid medical care of the patient has a positive impact on his health and reduces the treatment cost. Therefore, we have launched a prospective multicentric case-control study and investigated for urinary polypetides specific to acute (AHF) or chronic heart failure (CHF), using a capillary electrophoresis-mass spectroscopy strategy (CE-MS). Based on a screen of the urinary proteome of patients (CHF, AHF, and healthy controls matched for cardiovascular risk factors), we revealed a panel of polypeptides specific to HF. One polypeptide (X64, patent pending) seemed very relevant because it could discriminate AHF and CHF with a high specificity and specificity (AUC = 0,99; p<0,0001). X64 plasma levels were assessed within Atlanta (n=340, follow-up 3 years) and Toulouse (n=187, follow-up 6 years) cohorts. The Atlanta cohort revealed that X64 level is associated with major clinical events: HR: 1.23 per 100 ng/mL (95% CI: 1.06 to 1.43); P=0.005 and with HF admissions: IRR: 1.20 per 100 ng/mL (95% CI: 1.00 to 1.44); P=0.05. Moreover, the Toulouse cohort revealed that high X64 levels were strong predictors of cardiac death (p<0.0001). Our work provides with new biomarkers allowing for HF diagnosis in the BNP « grey zone » or prognosis and therefore allow for a better care of the HF patients at the hospital but also in general care.
Abstract 18730: Correlates and Cut-points of the Triglyceride/HDL Cholesterol Ratio: The Very Large Database of Lipids 4 (VLDL-4)
Authors: Manalac Raoul , Martin Seth S , Blaha Michael J , Toth Peter P , Kulkarni Krishnaji R , Nasir Khurram , Virani Salim S , Blumenthal Roger S , Jones Steven R
Published: April 2024

Background:
An elevated TG/HDL-C is predictive of atherosclerotic cardiovascular disease; however, advanced lipoprotein correlates of the TG/HDL-C ratio and discrimination by standard cut-points are incompletely characterized.

Hypothesis:
Elevated TG/HDL-C correlates most strongly with triglyceride-rich remnant lipoprotein cholesterol (RLP-C) and also with LDL density, Lp(a)-C, and male gender.

Methods:
We examined 1,350,908 individuals from the Very Large Database of Lipids (Baltimore, MD;
NCT01698489
) who were clinically referred for lipoprotein cholesterol ultracentrifugation (Atherotech, Birmingham, AL). LDL density was assessed as a continuous LDL density parameter (LLDR) calculated as the natural log of the ratio of dense to buoyant LDL-C subfractions. RLP-C was defined as VLDL
3
-C plus IDL-C.

Results:
The strongest univariate correlates of the TG/HDL-C ratio were VLDL
3
-C (spearman rho= 0.824, p<0.0001) and IDL-C (spearman rho=0.537, p<0.0001). In a multivariable linear regression model including age, gender, LLDR, Lp(a)-C, VLDL
3
-C, and IDL-C, the overall adjusted R
2
was 0.764 (p<0.0001). In this model, IDL-C was inversely correlated (partial R=-0.140, p<0.0001) while VLDL
3
-C (partial R=0.697, p<0.001) was more strongly and positively associated with TG/HDL-C. We compared demographic and lipid parameters across standard cut-points of TG/HDL-C (<3, 3-5, >5) (
Table
). Compared with the TG/HDL-C <3 group, there was a 36% higher VLDL
3
-C level in those with a TG/HDL-C of 3-5, and 73% higher level in those with a TG/HDL-C >5. There was a progressively higher LLDR across these groups characteristic of increasing LDL density.

Conclusions:
A higher TG/HDL ratio is correlated with an increasingly atherogenic lipid phenotype. Across increasing TG/HDL-C groups, VLDL
3
-C, IDL-C, and RLP-C increase. Non-HDL-C rises across these groups along with LDL density, despite similar LDL-C.