bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9150: Re-Elevation of Troponin Following Percutaneous Coronary Intervention Significantly Predicts 1-Year Mortality in Patients with High-risk Non-ST-Segment Elevation Acute Coronary Syndromes
Authors: Tricoci Pierluigi , Leonardi Sergio , White Jennifer A , Tinga Brian , Giugliano Robert P , White Harvey D , Armstrong Paul W , Kleiman Neal S , Sulimov Vitaly A , Tanguay Jean-François , Lewis Basil S , James Stefan K , Gibson C. M , Braunwald Eugene , Van de Werf Frans , Califf Robert M , Mahaffey Kenneth W , Newby L. K
Published: April 2024

Background:
The prognostic value of cardiac troponin (cTn) elevation post PCI is controversial. Moreover, in high-risk NSTE ACS patients presenting with elevated necrosis markers, the ability to use cTn to detect post-PCI MI is especially challenging: primarily this relates to discriminating PCI-related elevation from natural evolution of presenting MI. We addressed this issue by reviewing each cTn trend during the index ACS admission in all patients undergoing PCI randomized in the EARLY ACS (n=5552) and SYNERGY (n=4647) trials.

Methods:
Time and cTn value (indexed by ULN) data pairs were plotted into graphics for each of 10,199 pts and independently reviewed by 2 physicians to detect post-PCI cTn (re)elevation (example in figure). Post-PCI cTn peak was identified for each plot, and the relationship between peak cTn post PCI and 1-year mortality was evaluated using Cox proportional hazard modeling, correcting for the 15 clinical variables of the EARLY ACS 1-year mortality model (including baseline cTn).

Results:
Patients were classified into 3 groups: (i) (re)elevation post PCI not evaluable because cTn values rising through the time of PCI (group 1; N=4427 [43%]; excluded from further analyses); (ii) cTn values stable/falling with post-PCI (re)elevation detected (group 2; N=4276 [42%]); (iii) cTn values stable/falling but without post-PCI (re)elevation (group 3; n=1496 [15%]). In the multivariable model including patients in groups 2 and 3, peak cTn post PCI was significantly associated with a 7% increase in hazard of death per each 10xULN increase (adj. HR 1.07; 95% CI 1.03-1.11; p=0.0008).

Conclusion:
We describe a methodology that allows clear differentiation of post-PCI cTn (re)elevation from presenting MI in over half of high-risk NSTE ACS patients undergoing PCI. This approach identified a highly significant relationship between post-PCI cTn and 1-year mortality and has relevance for the incorporation of cTn for definition of post-PCI MI.
Abstract 9162: Echocardiographic Strain Imaging Allows Differentiation Between Heart Transplant Recipients with and Without Coronary Stenoses
Authors: Dandel Michael , Pang Chol-Ho , Wellnhofer Ernst , Knosalla Christoph , Hetzer Roland
Published: April 2024

Background:
Early detection of patients with cardiac allograft vasculopathy (CAV) is a major goal. However, because diffuse distal coronary narrowing is a major determinant of left ventricular (LV) dysfunction in CAV, regional wall motion alterations are less evident. Echocardiographic (ECHO) strain imaging reveals alterations in myocardial contraction not detectable by conventional ECHO. Thus, we assessed its reliability in distinguishing between patients with and without CAV.

Methods:
All consecutive transplanted patients without visible alterations of LV kinetics underwent speckle tracking derived 2D strain analyses at rest, before coronary angiography. LV radial, circumferential and longitudinal strain and strain-rate (Sr) were measured and also dyssynchrony and end-systolic dyssynergy indexes were calculated from strain curves. 2D strain data were tested for relationship to angiographic findings.

Results:
Of 187 evaluated patients, 56 had no CAV (group 1), 87 diffuse coronary type-B lesions (group 2) and 44 proximal focal stenoses (group 3). Whereas conventional ECHO showed no predictive value for coronary stenoses, certain strain and Sr parameters and indexes appeared predictive for detection of patients with CAV (Fig 1). Thus, the time to peak longitudinal Sr (TpLSr) and the peak longitudinal Sr/TpLSr index showed up to 93.1% and 94.6% sensitivity and specificity, respectively, for differentiation between group 1 and 2. The ayssynchrony and dyssynergy indexes for longitudinal shortening also allowed differentiation between group 2 and 3 (sensitivity and specificity: up to 86.3%).

Conclusions:
2D strain imaging is reliable for CAV prediction and also helpful for differentiation between patients with and without focal coronary stenoses. Our results recommend 2D strain as a non-invasive tool with the potential to facilitate early detection of stenoses and to enable angiographies to be timed, sparing patients frequent routine angiographies.
Abstract 9174: Global Variation in the Etiology and Management of Atrial Fibrillation: Results from a Global Atrial Fibrillation Registry
Authors: Healey Jeff S , Oldgren Jonas , Parekh Amit , Commerford Patrick J , Avezum Alvaro , Pais Prem , Zhu Jun , Jansky Petr , Sigami Alben , Morillo Carlos A , Liu Lisheng , Damasceno Albertino , Grinvalds Alex , Reilly Paul , Ezekowitz Michael , Wallentin Lars , Connolly Stuart J , Yusuf Salim
Published: April 2024

Background:
Atrial fibrillation (AF) is the most common arrhythmia worldwide. A truly global registry is needed.

Methods:
The AF registry enrolled unselected patients who presented to an emergency department with AF.

Results:
A total of 14,434 patients were enrolled: 45% with AF as their primary diagnosis and 36% with their first documented episode of AF. The number of sites and patients were: North America (18; 1787), Latin America (23; 1116), Western Europe (19; 1903), Eastern Europe (22; 2445), Middle East (8; 813), Africa (20; 891), India (24; 2450), China (20; 1905) and Asia (12; 1124). The average age of patients in North America was 70.2 years and 57.7 % of patients were male. Patients in Africa and India were 12 years younger and were more likely to be female. Hypertension was the most common risk factor, present in 62% of patients worldwide. Its prevalence ranged from 41.5% in India to 80.0% in Eastern Europe. Heart failure was the second most common risk factor, present in 35% of patients worldwide. Its prevalence ranged from 17.4% in India to 70.5% in Africa. Rheumatic heart disease was present in only 2.1% of North American patients with AF, compared to 15.3% in both the Middle East and China, 22.0% in Africa and 30.9% in India. In Africa, more than 5% of AF cases were associated with pericarditis or endomyocardial fibrosis, while these conditions were present in < 1% of patients elsewhere. In North America, the use of oral anticoagulation (OAC) among patients with AF and a CHADS
2
score of ≥ 2 was 72.6%. Elsewhere, the rate was from 19% in China to 63% in Eastern and Western Europe. For patients treated with OAC, the proportion of INR values between 2.0 and 3.0 ranged from 32.6% in India to 66.5% in Western Europe.

Conclusions:
Although advanced age, hypertension and heart failure are the most common predisposing conditions for AF in all regions, rheumatic heart disease remains an important cause in low-income countries. Appropriate use of OAC is low, particularly in low-income countries.
Abstract 9244: Depressive Symptoms and Related Health Behaviors May Contribute to Uncontrolled Hypertension
Authors: Persaud Glorian , Kee Renee , Akhand Sohana , Roemheld-Hamm Beatrix , Clemow Lynn
Published: April 2024

Introduction:
Depression has considerable support as a risk factor for hypertension and for blood pressure remaining uncontrolled even when treated; however, the pathways for depression's effect on hypertension are not well understood. One proposed mechanism is health behavior, including poor medication adherence, diet, physical activity, alcohol intake, and smoking, each of which have been related to depressive symptoms. An unanswered question is the extent of the relationship of depressive symptoms to health behavior in patients whose high blood pressure is uncontrolled.

Objective:
To explore potential links between depressive symptoms and health behaviors that contribute to uncontrolled high blood pressure.

Methods:
A total of 101 subjects classified as uncontrolled hypertensives by ambulatory blood pressure monitoring (waking mean > 135/85, on at least one antihypertensive drug), measured at baseline in a behavioral RCT for hypertension, completed the Beck Depression Inventory II (BDI), Rapid Eating Assessment for Patients (REAP), health behavior questions from the BRFSS, Pittsburgh Sleep Quality Index (PSQI), and Morisky Medication Adherence Scale (MAS). The relationship between the BDI score and health behavior scales and BMI were evaluated.

Results:
Depressive symptoms (BDI) correlated significantly with poorer medication adherence (r = 0.331, p = 0.001). Several dietary items often related to higher sodium intake also correlated with BDI scores: 1) consuming > 4 sit down or take-out meals from restaurants (r = 0.218, p = 0.029); 2) trouble being able to cook or shop (r = 0.229, p = 0.003); and 3) skipping breakfast (r = 0.20, p = 0.045). BDI scores were also highly correlated with PSQI items on duration of sleep (r = 0.508, p < 0.001) and dysfunctional sleep causing trouble staying awake, eating meals, engaging in social activities, or maintaining enthusiasm to get things done (r = 0.213, p = 0.037), not surprising as disrupted sleep can be a depressive symptom. BMI, physical activity, alcohol intake, and smoking were not related to BDI scores.

Conclusion:
Even mild-moderate levels of depressive symptoms (BDI mean = 6.53) affect medication adherence, diet, and sleep that can contribute to uncontrolled hypertension.
Abstract 9259: Upregulation of Cardiac Urotensin II (UII) Exacerbates UII Stimulation-Induced Negative Modulation on Myocyte Contractile Function and Ca
2+
Current in Streptozotocin-Induced Diabetic Rats
Authors: Cheng Heng-Jie , Zhou Peng , Zhao Weixin , Wajih Nadeem , Han Qing-Hua , Little William C , Cheng Che Ping
Published: April 2024

Background.
Urotensin II (U-II), a somatostatin-like peptide is a potent vasoconstrictor. It has been implicated in metabolic regulation. In diabetes mellitus (DM) patients, circulating UII levels are increased. Recent evidence suggests that UII plays a significant role in DM and its complications, such as diabetic cardiomyopathy. However, the mechanisms are unclear. Whether UII alters cardiac contractile behavior in DM is unknown. We tested the hypothesis that DM causes upregulation of myocyte UII and its receptors (UT). This may exacerbate UII stimulation-induced negative modulation on myocyte function and Ca
2+
current and contribute to the progression of left ventricular (LV) dysfunction in DM.

Methods.
We compared LV myocyte UII and UT expression, myocyte contractile, and L-type Ca
2+
current (I
Ca,L
) responses to UII stimulation in 8 rats at 6 weeks after receiving streptozotocin (STZ, 35 mg/kg, ip) and 8 age-matched normal control (C) rats.

Results.
Compared with controls, STZ-treated rats (DM rats) had more than 4-fold elevated blood glucose levels (DM: 569 vs C: 108 mg/dl) and reduced body weight followed by cardiomyocyte systolic and diastolic dysfunction with significant decreases in the peak velocity of myocyte shortening (dL/dt
max
) (28%, DM: 88.4 ± 5.2 vs C:122.7 ± 4.8 μm/s), relengthening (dR/dt
max
) (21%, -73.1 ± 4.9 vs -92.9 ± 6.0 μm/s), and I
Ca,L
(23%, 6.1 ± 0.2 vs 7.9 ± 0.3 pA/pF). Compared to normal myocytes, in DM myocytes, both UII (26%, DM: 0.58 vs C: 0.46) and UT (20%, 0.91 vs 0.76) mRNA and protein levels were significantly increased. Importantly, these changes were associated with enhanced UII-mediated negative modulation on myocyte contraction, relaxation, and I
Ca,L
. Compared to normal myocytes, in DM myocytes, superfusion UII (10
-5
M) caused significantly greater decreases in dL/dt
max
(DM: 24% vs C:11%) and dR/dt
max
(28% vs 14%) accompanied by significantly larger reductions in I
Ca,L
(19% vs 9.8%) (
P
<0.01).

Conclusions.
STZ-induced DM causes upregulation of cardiac UII system, which enhances inhibition of cardiomyocyte contraction, relaxation, and I
Ca,L
and, thus, may play an important role in the development and progression of diabetic cardiomyopathy.
Abstract 9292: Can Endothelial Progenitor Cell Dysfunction in Patients with Uncontrolled Diabetes be Normalized by Tight Glycemic Control?
Authors: Lev Eli , Zinger Joel , Leshem-Lev Dorit , Merav Rigler , Dadush Oshrat , Battler Alexander , Kornowski Ran
Published: April 2024

Background:
Recent evidence has shown that endothelial progenitor cells (EPCs) have an important role in repair process following vascular injury, and that in patients (pts) with diabetes EPCs number and function are reduced. Small studies suggest that tight metabolic control may improve the properties of EPCs in pts with uncontrolled diabetes. However, it is unclear whether following such intensive control EPC properties approach the levels of subjects without diabetes. We, therefore, aimed to examine whether after intensive glycemic control EPCs number and function are similar to the EPC profile in non-diabetics.

Methods:
Twenty five pts with treated diabetes who underwent intensive glycemic control for a period of 3-4 months (initial HgA1C > 8.5%; HgA1c goal < 7%) were compared to 25 matched non-diabetic subjects. The proportion of peripheral mononuclear cells (PMNCs) expressing VEGFR-2, CD133 and CD34 were evaluated by flow cytometry. EPCs colony forming units (CFUs) were grown from PMNCs, characterized and counted following 7 days of culture. Functional properties of the cultured cells were evaluated by the MTT viability assay, and migration - modified Boyden assay.

Results:
The two groups (n=25 each) were well-matched: mean age 59.5-61.5 years, 20% women and BMI of 29-31. All pts were treated with aspirin and statins. At baseline pts with diabetes had significantly lower levels of circulating EPCs and reduced functional properties compared with the non-diabetic subjects. After the tight control period HgA1C decreased from 9.5% to 8%, and circulating EPCs increased to a level similar to the non-diabetic group (VEGFR-2
+
CD34
+
:

1.12±0.15% vs. 1.14±0.14%; VEGFR-2
+
CD133
+
:

0.66±0.11% vs. 0.72±0.11%, respectively). However, the number of EPC CFUs in the diabetes group after the control period remained lower compared to the non-diabetes group (10.96±1.71 vs. 15.4±1.9 colonies per well, respectively, P=0.001). Furthermore, the MTT viability test and migration were also reduced in the diabetic compared with the non-diabetic group.

Conclusions:
Following a period of tight glycemic control in pts with diabetes numbers of circulating EPCs increase to a level similar to that of subjects without diabetes, but their functional properties remain attenuated.
Abstract 9593: Osteoclastogenesis as a Novel Therapeutic Target for Abdominal Aortic Aneurysm
Authors: Yamanouchi Dai , Stair Colin , Morgan Stephanie , Kent K. Craig
Published: April 2024

Arterial calcification has been proven to be the result of highly organized processes as seen in bone which relies upon a delicate balance between osteoblasts and osteoclasts. Osteoclast-like cells (OLCs) are derived from the monocyte/macrophage lineage and share features of osteoclasts, including the ability to dissolve extracellular matrix. Although osteoclastogenesis has been reported to occur in calcified arteries, its potential role in the development of abdominal aortic aneurysm (AAA) has yet to be explored. Here, we examined the role of OLCs in the development of AAA. Firstly, we obtained aortic tissues from patients undergoing surgical repair for AAA (N = 5) and aortic occlusive disease (N = 5). Alizarin-Red staining showed calcification in both aneurysmal and occlusive aorta. In contrast, OLCs, recognized as multi-nucleated cells positive for enzymatic TRAP staining, were identified only in aneurysmal aorta (100%, 5 of 5). A time course experiment in mouse calcium chloride-induced AAA (CaCl2 AAA) showed calcium deposition and monocyte/macrophage accumulation starting at 48 hours post-surgery followed by OLC formation, peaking 7 days after CaCl2 injury. Secondly, we administered bisphosphonate (Zoledronic acid, 0.1 mg/kg, once), an inhibitor of osteoclasts, or normal saline as a control, intravenously to mouse after CaCl2 injury (N = 3). Bisphosphonate-treated mice showed a significant reduction in arterial dilation after 7 and 42 days with a mean fold change of 1.08 ± 0.09 vs. 1.62 ± 0.05 (P < 0.01) and 1.24 ± 0.12 vs. 2.26 ± 0.06 (P<0.01), respectively. We also studied the effect of bisphosphonate on “developed aneurysm” by delaying the injection until one week after the injury (N = 5). Bisphosphonate significantly delayed a further expansion of the aneurysm with a percent increase from 7 to 42 days of 11.5% vs. 63.6% (P < 0.01). Finally, mice treated with a neutralizing antibody to RANKL (1mg/kg), a key factor for osteoclast differentiation, showed a significant inhibition at 7 days (N = 3) (1.19 ± 0.06 vs. 1.62 ± 0.05, P < 0.01). In conclusion, we have demonstrated the existence of OLCs in AAA and the inhibitory effect of bisphosphonate and anti-RANKL antibody on aneurysm. These results suggest that OLCs could be a novel therapeutic target for AAA.
Abstract 9600: Coronary Artery Disease Patients with Normal Body Mass Index but Central Obesity Have the Worst Long-Term Survival When Compared to Other Patterns of Adiposity
Authors: Coutinho Thais , Goel Kashish , Correa de Sa Daniel , Kragelund Charlotte , Kanaya Alka , Zeller Marianne , Park Jong Seon , Kober Lars , Torp-Pedersen Christian , Cottin Yves , Lorgis Luc , Lee Sang-Hee , Kim Young-Jo , Thomas Randal , Roger Veronique , Somers Virend , Lopez-Jimenez Francisco
Published: April 2024

Introduction:
In patients with coronary artery disease (CAD), mortality risk increases directly with central obesity (waist circumference [WC] or waist-hip ratio [WHR]) and inversely with BMI (“obesity paradox”). We hypothesized that CAD patients with normal BMI but centrally obese would have increased risk of death compared to other patterns of adiposity.

Methods:
We studied 15,923 subjects with established CAD who were part of 5 studies from 3 continents. We excluded 373 participants with BMI <18.5 Kg/m
2
and 3863 without either WC or WHR data. Subjects were divided in 6 categories based on BMI (normal, overweight or obese) and either WC or WHR (normal or high). Multivariate Cox-proportional hazard models adjusted for age, sex, BMI, hypertension, diabetes, smoking, heart failure, creatinine level and use of aspirin, beta-blockers, and inhibitors of the renin-angiotensin system assessed mortality risk according to different patterns of adiposity, using subjects with normal BMI and normal WC or WHR as reference.

Results:
Mean age was 65.7±11.0 yr, and 55% were men. There were 4699 deaths, median follow-up 4.7 years (IQR: 0.5 - 7.6 years). Results are summarized in the Table. Subjects with normal BMI but centrally obese had the worst long-term survival when compared to subjects with other patterns of adiposity. Furthermore, normal weight centrally obese subjects had 1.92 higher risk of dying than individuals with overweight BMI but normal WHR, and 1.63 higher mortality risk than subjects with obese BMI but normal WHR (
P
<0.002 for both).

Conclusions:
Normal weight with central obesity, a body morphology pattern often clinically dismissed, is associated with the highest mortality in patients with CAD, especially when compared to individuals considered overweight or obese but without central obesity. An adverse metabolic milieu or less attention to risk assessment/modification in the setting of normal weight central obesity may explain these findings.
Abstract 9693: Onset of Lone Atrial Fibrillation Before 40 Years is Associated with a High Prevalence of Mutations in the Cardiac Sodium Channel
Authors: Olesen Morten S , Yuan Lei , Nielsen Jonas B , Liang Bo , Holst Anders , Schmitt Nicole , Christiansen Michael , Olesen Søren-Peter , Haunsø Stig , Jespersen Thomas , Svendsen Jesper H
Published: April 2024

Introduction
Atrial Fibrillation (AF) is the most common sustained arrhythmia. Studies screening SCN5A, the gene encoding the α-subunit of the cardiac sodium channel, have reported that around 0-2 % of general AF patients have mutations in the gene.

Hypothesis
We tested the hypothesis that early onset lone AF is associated with a high prevalence of genetic variation in SCN5A and CAV3, both genes encoding important components of the cardiac sodium channel.

Methods
We sequenced the coding region and splice-site of SCN5A and CAV3 in 192 early onset lone AF patients. Only lone AF patients with onset of disease before the age of 40 years and without traditional risk factors for AF were included; patients with structural heart disease, diabetes or metabolic diseases or other disease were excluded. For electrophysiological patch clamp studies HEK cells were transiently co-transfected with pcDNA3-hSCN5A, and pcDNA3-eGFP as a reporter gene.

Results
Of 192 probands with early onset lone AF, nine non-synonymous mutations were found in ten probands: eight mutations in SCN5A; T220I, R340Q, T1304M, F1596I, R1626H (novel), D1819N, R1897W (novel), V1951M and one mutation in CAV3 (T78M in two patients). None of the mutations were present in public available databases and only V1951M has previously been reported in conjunction to AF. All other mutations affected evolutionarily conserved residues. All patient caring SCN5A mutations underwent a flecainide test, without inducing any sings of Brugada ECG pattern. SCN5A, T220I, T1304M and CAV3 T78M has been electrophysiologically investigated earlier and the mutations all significantly compromises sodium current. In vitro electrophysiological studies were conducted of the remaining mutations. R340Q, R1626H and R1897W showed loss-of-function while T1304M showed gain-of-function. F1596I did not affect the electrophysiologic function while V1951 showed both loss-of-function and gain of function.

Conclusions
Ten out of 192 patients with early-onset lone AF had a non-synonymous mutation in SCN5A and CAV3. All ten mutations either had been or were investigated electrophysiologically and of those, seven mutations compromised the sodium current and are therefore suspected to enhance the susceptibility to AF.
Abstract 9827: Acute Rosiglitazone Treatment is Cardioprotective Against Ischemia/Reperfusion Injury by Modulating AMPK, Akt, and JNK Signaling in Non-Diabetic Mice
Authors: Morrison Alex , Yan Xiaoyan , Li Ji
Published: April 2024

Background:
Rosiglitazone (RGZ), a PPAR-γ agonist, has been demonstrated to possess cardioprotective properties during ischemia/reperfusion (I/R). However, this concept remains controversial as recent evidence has suggested an increased risk of cardiac events associated with long-term use of RGZ in patients with type 2 diabetes. In this study, we tested the hypothesis that acute RGZ treatment is beneficial during I/R by modulating cardioprotective signaling pathways in a non-diabetic mouse model.

Methods and Results:
Non-diabetic FVB/NJ mice were subjected to left anterior descending coronary artery occlusion for 20 min followed by 4 h of reperfusion and given RGZ (1 µg/g i.v.) 5 min before reperfusion. Myocardial infarction was significantly reduced in mice treated with RGZ compared to vehicle controls (9% ± 1% vs. 20% ± 4%,
P
<0.05) and post-ischemic recovery in isolated perfused hearts (no flow ischemia 20 min, reperfusion 30 min) was significantly improved with RGZ administered at reperfusion compared to vehicle (
P
<0.001). To investigate the signaling mechanisms of RGZ-induced cardioprotection, mice were subjected to 20 min of
in vivo
regional ischemia and 10 min of reperfusion. The levels of both p-AMPK (Thr
172
) and p-Akt (Ser
473
) were significantly increased when RGZ was given 5 min before reperfusion compared to vehicle (
P
<0.01 and
P
<0.05, respectively). On the other hand, p-JNK (Thr
183
/Tyr
185
) was significantly decreased as a result of RGZ treatment compared to vehicle (
P
<0.05). Pre-treatment with the selective PPAR-γ inhibitor GW-9662 (1 µg/g i.v.) 10 min before reperfusion significantly decreased both p-AMPK and p-Akt levels and did not decrease p-JNK levels in the heart during I/R. Moreover, mice pre-treated with the AMPK inhibitor compound C (10 μ g/g i.p.) and given RGZ 5 min before reperfusion did not exhibit a significant decrease in infarct size compared to RGZ alone.

Conclusions:
Taken together, acute treatment with RGZ can reduce ischemic injury in a non-diabetic mouse heart via modulating AMPK, Akt, and JNK signaling pathways. Although the use of RGZ pertains exclusively to patients with type 2 diabetes, the use of acute RGZ therapy to non-diabetic patients may be a potential beneficial treatment for I/R injury.
Abstract 9885: Progressive Worsening of Left Ventricular Size and Function is Associated with Increased Ventricular Arrhythmia Burden Among Patients Undergoing Cardiac Resynchronization Therapy
Authors: Friedman Daniel J , Altman Robert K , Park Mi Young , Orencole Mary , Britt Carmella M , Picard Michael H , Ruskin Jeremy N , Singh Jagmeet P , Heist Edwin K
Published: April 2024

Background
Ventricular tachycardia and fibrillation (VT/VF) may increase as systolic heart failure worsens. The effect of progressive decline in LV function despite cardiac resynchronization therapy (CRT) on the incidence of VT/VF has not been described.

Methods
The relationships between changes in LV size and function and incident VT/VF were analyzed in 115 patients who underwent CRT implant. Baseline and 6 month post-CRT echocardiograms were used to determine LV remodeling. Progressors were defined by both increase in LV end-systolic dimension (LVESD) and decrease in left ventricular ejection fraction (LVEF) after CRT. Responders were defined as >5% absolute increase in LVEF or 10% decrease in LVESD, and all other patients were defined as Non-Progressors. The primary endpoint was time to VT/VF requiring device therapy for 5 years after CRT implant.

Results
At 6 months, 67% of patients were Responders, 22% were Non-Progressors and 11% were Progressors. There were no baseline differences between the 3 groups in medications, comorbidities, LVEF, LVESD, cardiomyopathy type, NYHA class, prior VT/VF, or renal function. Progressors were at significantly increased risk of VT/VF compared to either Non- Progressors (p=0.0431) or Responders (p = 0.0018)(figure). There was no significant difference in VT/VF comparing Non-Progressors to Responders (p=0.4151).

Conclusions
CRT patients with worsening in both LV size and function 6 months after CRT placement have a significantly increased incidence of VT/VF compared to patients with no change or improvements in these parameters. “Progressors” despite CRT thus represent a high-risk population for VT/VF who warrant close follow-up.
Abstract 9887: Patient Selection for Ventricular Assist Device Therapy in the Elderly: Application of the HeartMate II Risk Score
Authors: Cowger Jennifer A , Sundareswaran Kartik , Rogers Joseph G , Kushwaha Sudhir S , Pagani Francis D , Tatooles Antone , Adamson Robert M , Slaughter Mark S , Farrar David J
Published: April 2024

Introduction:
Advanced age is a risk factor for poor outcomes following left ventricular assist device (LVAD) implant. A means of identifying elderly patients with acceptable mortality risk following LVAD surgery is not currently available. The HeartMate II (HMII) Risk Score (HMRS) was recently developed and validated, providing good risk discrimination for predicting survival in patients undergoing HMII implant. Independent survival predictors in the model included age and markers of renal function, coagulopathy and nutrition. We hypothesize that the HMRS will provide utility for risk stratification of the elderly LVAD candidate.

Methods:
Elderly patients (age >65 years) enrolled into the HMII Destination Therapy (DT) and Bridge to Transplant trials were selected for the study (n=444). Complete data for HMRS calculation was available in 98% (n=435). Preoperative patient HMRS was calculated according to the formula: HMRS = ln(1.29)*decade of age + ln(0.71)*Albumin + ln(1.37)*Cr + ln(1.86)*INR + ln(0.52)*LVAD Center Volume >=15 + ln(0.67)*Implant after 2007. Patients were trichotimized into high (HMRS >1.0), medium (HMRS 0.50-1.0), and low (HMRS <=0.50) risk categories (as previously defined in model development) based on HMRS. The primary endpoint was survival at 1 year following LVAD implant, estimated using Kaplan-Meier methods.

Results:
The mean cohort age was 71±4 years and 84% (n=372) had devices implanted for DT. The table shows the HMRS along with mean±stddev values for the score's components. All between-group differences were statistically significant (Kruskal-Wallis p<0.05), although differences in age were not clinically significant. Survival based on HMRS strata is shown in the figure. Patients in the low and medium risk groups had survivals >80% at 1 year following LVAD implant.

Conclusions:
The HMRS can be used to identify elderly patients with survivals comparable to that of the general LVAD population.
Abstract 9995: Glucagon-Like-Peptide-1 (GLP-1) Activates AMP-Activated Protein Kinase (AMPK) and Diminishes Inflammation in Human Aortic Endothelial Cells (HAECs)
Authors: Krasner Nadia M , Ido Yasuo , Ruderman Neil B , Cacicedo Jose M
Published: April 2024

GLP-1 therapy is primarily prescribed for patients with type 2 diabetes because of its effects on insulin and glucagon secretion resulting in improved glucose control. Recent epidemiological evidence strongly suggests that it may also have cardio- and cerebrovascular benefits; however, the mechanisms responsible for these benefits are not known. AMPK has been implicated as a target for the prevention of cardiovascular disease by virtue of its involvement in lipid metabolism as well as its ability to suppress inflammation and other atherogenic factors. In the present study we examined whether GLP-1 activates AMPK in HAECs and if so, whether it also downregulates inflammatory and atherogenic factors. Initial RT-PCR studies revealed that HAECs express the primary enzyme responsible for GLP-1 degradation, dipeptidyl peptidase-4 (DPP4), the GLP-1 receptor (GLP-1R) and several targets of the GLP-1R signaling cascade. Thus, these cells possess the machinery necessary to transduce GLP-1 signals. Dose and time course experiments revealed that the concurrent addition of GLP-1 at a concentration of 0.3nM, led to the transient activation by phosphorylation of AMPK and its substrate ACC, which peaked at 15 minutes, returned to baseline by 30 minutes and cyclically rose again by 50 minutes. Incubation of HAECs for 24h in a hyperglycemic media (25mM) led to augmented gene levels of vascular cellular adhesion molecule-1 (VCAM-1) and E-selectin, molecules known to be increased during the course of atherogenesis. GLP-1 addition markedly downregulated both the control level and glucose-stimulated increase in VCAM-1 and E-selectin expression observed at 24h. Repetition of this trial using TNFα treatment to induce inflammation showed similar downregulation of VCAM-1/E-selectin expression attributable to GLP-1 addition. Further studies are needed to determine whether the sustained effect of GLP1 is attributable to AMPK, and if so, whether it works by acute effects on metabolism and/or the regulation transcriptional activators and co-activators.
Abstract 18300: Myocardial Ischemia Induces Telomerase Activity in the Mouse Heart
Authors: Werner Christian , Arendt Christophe , Bakogiannis Constantinos , Schirmer Stephan H , Mueller Andreas , Boehm Michael , Laufs Ulrich
Published: April 2024

Introduction: The incidence of cardiovascular disease rises with age. Ischemia and oxidative stress-induced DNA damage and telomere erosion may accelerate cardiac senescence. The enzyme telomerase has been shown to protect cardiovascular cells from mitochondrial oxidative stress independent of telomere elongation. We examined whether myocardial ischemia impacts on telomere biology and cellular aging in the infarcted mouse heart.

Methods and results: C57Bl/6 mice (10 weeks old, n=6-8 per group) were subjected to anterior myocardial ischemia induced by proximal ligation of the left anterior descendant coronary artery or sham operation. Cardiac MRI was used to verify infarct localization and measure LV function, showing that ejection fraction was reduced in MI mice (47±5% vs. 68±3% in sham, p<0.01). Sham and MI mice were compared 3 days, 7 days, or 4 weeks after LAD ligation and myocardial infarct zone (IZ) and remote zone (RZ) were analyzed. Telomerase activity as measured by TRAP assays was elevated in the infarct zone 3 days after LAD ligation (187±9% vs. sham mice, p<0.01), but not in the remote zone (113±35%). Seven days after myocardial infarction, telomerase was up-regulated both, in the infarct zone (177±31%) and the remote zone (154±26%). This effect was even more pronounced 4 weeks after LAD ligation (IZ: 271±14%; RZ 223±28%). In concert with telomerase activation, telomere repeat binding factor (TRF) 2 protein expression was up-regulated in the infarct zone after three days (337±25%) and in both areas after 7 days (IZ: 431±48%; RZ: 380±31%) and less strongly after 4 weeks (IZ: 170±23%; RZ: 141±27%). In parallel to telomerase activity and TRF2 expression, the apoptosis and senescence markers p53 (189±11%), Chk2 (167±32%), bax/bcl2-ratio (278±27%) and p16 (518±42%) were up-regulated in the myocardium of MI mice after 4 weeks (all shown values p<0.05 vs. myocardial tissue of sham-operated mice).

Conclusion:
Myocardial telomerase and telomere-associated factors are up-regulated in a time- and region-specific manner in the infarcted mouse heart in concert with apoptosis and cell-cycle regulators. This regulatory process may be of relevance for myocardial survival, inflammation, and remodelling after ischemia.
Abstract 18310: Angiotensin Converting Enzyme Gene Polymorphism is Associated with Reverse Remodeling of Left Atrium after Catheter Ablation of Atrial Fibrillation
Authors: Shim Jaemin , Mun Hee-Sun , Wi Jin , Park Jae Hyung , Uhm Jae Sun , Kim Jong Youn , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam
Published: April 2024

Background:
Although it has been known that radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) induces reverse remodeling of left atrium (LA) and improves left ventricular (LV) function, its mechanism has not been evaluated yet. We hypothesized that genetic polymorphisms in angiotensin converting enzyme (ACE) or angiotensin II type 1 receptor (AT1R) genes may contribute to the changes after RFCA.

Methods:
We included 263 patients with AF (male 78%, 56±11 years old, paroxysmal AF 70%) who underwent RFCA of AF, and compared pre-procedural and post-RFCA 1-year follow-up echocardiography. LA reverse remodeling was defined as decreased LA size at 1-year after RFCA. Potential 4 ACE (rs4341, rs4362, rs4309, rs4291) and 3 AT1R (rs2675511,
rs422858
, and rs5182) related single nucleotide polymorphisms (SNPs) were genotyped and compared with phenotypes of AF patients.

Results:
Mean LA size decreased (41.4±6.1 vs. 38.5±5.8 mm, p<0.001) at 1-year after RFCA and the reduced LA size after RFCA was observed in 72.2% of patients (n=190). The patients with reverse remodeling were more likely to have larger preprocedural LA size (42.6 ± 5.9 vs. 38.4 ± 5.3 mm, p<0.001) than those without it. Mean LV ejection fraction (LVEF, 63.3±7.8 vs. 65.2±7.5%, p<0.001) increased at 1-year and E/E’ decreased (18.7±4.0 vs. 14.6±3.3 mm, p<0.001) in patients with baseline LV diastolic dysfunction (E/E’≥15). Among the 7 SNPs, ACE gene, rs4309 and rs4291 variants, were significantly associated with reverse remodeling of LA (CC vs. CT+TT; OR 0.407; 95% CI 0.189-0.879, TT vs. AT+AA; OR 0.307; 95% CI 0.114-0.827, respectively). A multiple logistic regression analysis showed that the rs4309 variant (OR 0.400; 95% CI 0.179-0.896) and preprocedural LA size (OR 1.147; 95% CI 1.083-1.215) were independent predictors of the reverse remodeling of LA.

Conclusions:
Reduction of AF burden by catheter ablation induces reverse remodeling of LA and improves LV systolic and diastolic function, especially in patients with baseline LV diastolic dysfunction. Several ACE polymorphisms were associated with such reverse remodeling of LA in patients with AF.
Abstract 18313: Gender Differences in the Early Mortality of Octogenarian Patients with Acute Myocardial Infarction From a Registry Database in Japan
Authors: Yamane Takafumi , Kotani Junichi , Sakamoto Hiroki , Ishihara Masaharu , Anzai Toshihisa , Shimizu Wataru , Yasuda Satoshi , Kusuoka Hideo , Yokoyama Hiroyuki
Published: April 2024

Background:
During the previous 2 decades studies have consistently shown that younger women hospitalized with an acute myocardial infarction (AMI) have a poorer prognosis than their men peers. However, gender differences in elderly patients especially in octogenarians are not fully discussed. We evaluated gender differenes in ogtogenarians patients with AMI in Japan, which is highly progressive aging society.

Methods and Results:
We established the multicenter registry to collect data of patients with AMI. 3691 patients enrolled into a registry from 27 hospitals during 2005 and 2009. Among these patients, 755 patients were octogenarians ( age equal or older than 80), and 383 were male and 372 were female. Female was more likely to be older (84.2±3.9 vs 85.7±4.3, p<0.0001) and longer from the onset of symptom to admission, more likely to have heart failure in admission. However, there was no change in the rate of hypertension, dyslipidemia, diabetes between both gender. Primary percutaneous coronary intervention (PCI) was performed at a high frequency in both groups (male vs female, 78.9% vs 75.5%, p=0.28). In patients with AMI female <80 years old had higher in-hospital mortality than male of the same age (male vs female, 4.4% vs 9.5%, p<0.0001), but not in octogenarian patients (male vs female, 14.6% vs 19.9%, p=0.055). In multivariable analysis, female was stronger predictor of in-hospital mortality in non-octogenarian patients (Odds Ratio 2.7, 95%CI 1.6-4.3, p<0.0001), than in octogenarian patients (Odds Ratio 1.4, 95%CI 0.78-2.4, p=0.27).

Conclusions:
In octogenarian AMI patients, gender differences of baseline characteristics are not so strong as non-octogenarian patients, and female was not so strong predictor of in-hospital mortality.
Abstract 18317: Abnormal High Density Lipoprotein (HDL) from Patients with Chronic Kidney Disease (CKD) Increases Arterial Blood Pressure: Role of Toll-Like Receptor-2 (TLR-2)
Authors: Speer Timo , Rohrer Lucia , Blyszczuk Przemyslaw , Kränkel Nicolle , Kuschnerus Kira , Shi Yi , Akhmedov Alexander , Zewinger Stephen , von Eckardstein Arnold , Lúscher Thomas , Bahlmann Ferdinand , Fliser Danilo , Landmesser Ulf
Published: April 2024

Background Patients with chronic kidney disease (CKD) exhibit a high cardiovascular morbidity and mortality, even in the early stages, and frequently develop hypertension. , Patients with advanced CKD have an uremic dyslipidemia, characterized by low levels of total cholesterol, low density lipoprotein and HDL cholesterol and elevated levels of triglycerides. In addition to its role in reverse cholesterol transport, HDL from healthy subjects (HS) exerts several potential vasoprotective effects. Thus, we compared endothelial effects of HDL from CKD patients and HS and potential consequences for blood pressure responses. Methods HDL was isolated from patients with CKD (K/DOQI stadium II, IV, V, each n=15) and healthy subjects (n=15) by sequential ultracentrifugation. The effect of HDL on endothelial nitric oxide production (NO) was assessed by electron spin resonance (ESR) spectroscopy. To evaluate the effects of HDL on systolic blood pressure (SBP) in vivo, HDL was injected into wild type and eNOS-deficient mice. Expression of VCAM-1 and endothelial mononuclear cell (MNC) adhesion was assessed. Moreover, endothelial repair capacity of HDL was assessed in vitro and vivo, using a gap closure assay and carotid injury model in nude mice . Results HDL from HS stimulated endothelial NO production; whereas HDL from CKD patients markedly inhibited the endothelial NO production (-80 % by HDL of these patients; P<0.05), even in incipient CKD. TLR2, but not TLR4 inhibition, prevented the inhibitory effects of HDLCKD on endothelial NO production. In vivo, CKD-HDL induced an increase of SBP (+10.7±1.1 mmHg; P<0.05), while healthy HDL reduced SBP (-11.3±1.7, P<0.05). Notably, HDL from patients with CKD induced endothelial VCAM-1 expression and promoted endothelial MNC adhesion, while HDL from healthy subjects did not. In vitro gap closure and in vivo reendothelialization after carotid injury were suppressed by HDL of CKD patients. Conclusion Our data demonstrate for the first time that endothelial-protective effects of HDL are considerably impaired in patients with CKD independently of the severity of CKD. Furthermore, HDL may be involved in initiation and aggravation of hypertension in these patients.
Abstract 18388: Is Pregnancy Associated with an Increased Risk of Arrhythmias and Disease Progression in Arrhythmogenic Right Ventricular Cardiomyopathy?
Authors: Rigato Ilaria , Rigato Sara , Steriotis Alexandros Klavdios , Zorzi Alessandro , Basso Cristina , Thiene Gateano , Iliceto Sabino , Corrado Domenico , Bauce Barbara
Published: April 2024

BACKGROUND:The risk of pregnancy in women with ARVC is an important clinical issue for which systematic data have not been reported so far.

OBJECTIVES: to assess the morbidity and mortality in nulliparous and multiparous women affected by Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC).

METHODS: The study cohort included 27 women affected by ARVC with one or more live births, for a total of 47 live births. Maternal mortality and morbidity related to ARVC during pregnancy was evaluated with a follow-up programme, consisting of personal and family history, ECG, signal-averaged ECG, 24-h Holter and echocardiogram within three years of their pregnancy. The symptoms considered were dyspnoea, asthenia and palpitations. Moreover in 15 patients with >1 pregrancies, clinical and instrumental findings detected at the time of the first and the second pregnancy were compared. Finally, data of 13 nulliparous ARVC patients (mean age 32,3±5yrs) were correlated to those of 10 multiparous patients with the same age (34,9± 3,3 yrs).

RESULTS: No pregnancy-related death occurred. In the 27 patients evaluated within close proximity of their first pregnancy, 4 (14%) showed worsening of arrhythmias during pregnancy. All 4 patients had severe form of the disease. One patient experienced a sustained ventricular tachycardia 50 days after delivery. No patient complained of worsening symptoms. In the 15 patients who had more than one pregnancy, the comparison between the first and the second pregnancy demonstrated worsening of symptoms (P=0,05) and arrhythmias (P=0,03) after the second delivery. Similarly, the comparison between nulliparous and mutiparous ARVC patients demonstrated a significant dilatation of the Right Ventricular Outflow Tract (RVOT1= 21mm/m2; p=0,03) as well as worsening of symptoms (P=0,05) and arrhythmias (p=0,03) after the second pregnancy.

CONCLUSIONS: Maternal mortality is not increased in patients with ARVC compared with the general population. During gestation a worsening of arrhythmic pattern is more common in subjects with a severe form of the disease. A second pregnancy seems to be associated with worsening of clinical and instrumental features of the disease. Pre-conception planning and risk assessment are essential.
Abstract 18406: Gender Influence on the Functional Significance of Intermediate Coronary Artery Stenosis
Authors: Lee Ju-Hee , Koo Bon-Kwon , Park Kyung-Woo , Itsik Ben-Dor , Waksman Ron , Pichard Augusto , Nam Chang-Wook , Doh Joon-Hyung , Murata Naotaka , Tanaka Nob , Lee Chi-Hang , Gonzalo Nieves , Escaned Javier , Costa Marco A , Kubo Takashi , Akasaka Takashi , Hu Xinyang , Wang Jian-An , Yang Hyung-Mo , Yoon Myeong-Ho , Tahk Seung-Jae , Kim Hyo-Soo
Published: April 2024

Background
Previous studies suggest that there are clinically relevant differences between women and men in patients with ischemic heart disease. However, little is known about the gender influence on the functional significance of coronary artery stenosis.

Method
A total of 1,032 lesions with available intravascular ultrasound (IVUS) and fractional flow reserve (FFR) were recruited from 11 international centers and 881 de novo lesions with intermediate stenosis located at the non-left main major epicardial coronary arteries (822 patients, male 70.6%) were included in this analysis. All data were analyzed at Seoul National University Data Management Core Laboratory. FFR ≤0.8 was considered functionally significant.

Results
Angiographic % diameter stenosis and reference diameter were 49.6±12.7 and 3.0±0.5 mm, respectively. Minimum luminal area (MLA) by IVUS was 3.12±1.34mm
2
. Mean FFR was 0.81±0.11 and 353 lesions (40.1%) were functionally significant. There were no differences in angiographic lesion severity and IVUS MLA between male and female patients (Table). However, compared to female patients, FFR was significantly lower in male (male: 0.81±0.11 vs. female: 0.83±0.10,
P
=0.010) and functionally significant stenosis was more frequent in male patients (FFR ≤0.8; male: 42.8% vs. female: 32.9%,
P
=0.007). The best cutoff value of angiographic % diameter stenosis to determine the functional significance was 49.4% in male and 53.0% in female patients. The best cutoff value of IVUS MLA was 3.25 mm
2
in male and 3.05 mm
2
in female patients.

Conclusion
Compared to male patients, female patients may have higher anatomical threshold for the functional significance of coronary artery stenosis.
Abstract 18531: Impact of MicroRNA-145 to Prevent Vein Graft Disease in Rabbit by Regulation of Smooth Muscle Cell Phenotype
Authors: Ohnaka Motoaki , Marui Akira , Yamahara Kenichi , Minakata Kenji , Yamazaki Kazuhiro , Kumagai Motoyuki , Masumoto Hidetoshi , Ikeda Tadashi , Sakata Ryuzo
Published: April 2024

Backgrounds Intimal hyperplasia is the major cause of vein graft disease. Smooth muscle cell (SMCs) proliferation and migration into the intima are key mechanism in this process. Recent studies have reported that microRNA-145(miR-145) is a specific mediator in the regulation of proliferation, differentiation, and phenotype of SMCs. In this study, we sought to investigate the impact of miR-145 to intimal hyperplasia in rabbit model of vein graft disease using electropolation mediated gene transfer.

Methods and Results Right jugular vein of male Japanese white rabbit was harvested (15mm) and endothelial cells of the graft were injured by balloon catheter. The graft was interposed in ipsilateral jugular artery in reversed fashion (Control group). Alternatively, harvested jugular vein was transduced with miR-145 encoding plasmids by electroporator after balloon injury, and then interposed in ipsilateral jugular artery in the same fashion (miR-145 group). Two weeks after surgery, venous graft was explanted. Four sections were obtained and each section was stained with both hematoxylin and eosin, and the elastica van Gieson method for elastic fiber staining. Neointima formation was quantified on cross sections of vein graft and reendothelialization and intima/media area ratio were evaluated. Optimal condition of the electroporator (Figure 1a) was confirmed by DsRed immunostaining (Figure 1b: positive red fluorescence on inner surface of the graft 1c: DsRed monoclonal antibody staining). Reendothelialization was significantly reduced in miR-145 transduced grafts at 2 weeks (Figure 1d, 1e). Arrowheads indicate the internal lamina. Intima/media area ratio was significantly lower in the miR-145 group compared to the control group (0.062±0.011 vs. 0.365±0.281, p=0.03) .

Conclusion Transduction of miR-145, which specifically regulates smooth muscle cell phenotype, into the bypass graft may be a novel option to prevent intimal hyperplasia in vein graft disease.