bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14194: Health-related Quality of Life After Out-of-hospital Cardiac Arrest : Analysis of the Parisian Registry
Authors: Geri Guillaume , Dumas Florence , Bonnetain Franck , Bougouin Wulfran , Champigneulle Benoit , Arnaout Michel , Chiche Jean Daniel , Pène Frédéric , Mira Jean-Paul , Empana Jean-Philippe , Cariou Alain
Published: April 2024

Introduction:
Data on health-related quality of life (HRQOL) of resuscitated out-of-hospital cardiac arrest (OHCA) patients remain scarce. Our aims were to compare long-term HRQOL of OHCA with that of the general population, and to assess factors associated with better HRQOL.

Methods:
We used a large cohort of OHCA patients admitted in a tertiary medical intensive care unit. The main outcome was HRQOL (SF-36 questionnaire). Each OHCA case was matched with 4 controls of same age and sex issued from general French population. The associations between pre and intra hospital variables and early interventions with the SF-36 dimensions were investigated using MANCOVA.

Results:
During the study period (2000-2013), 1829 OHCA patients were admitted and 602 have been discharged alive. SF-36 interview took place 50 [22-93] months after OHCA. Between discharge and the interview, 137 patients died, 210 were lost of follow-up and then 255 (median age 55 [45,64] y., mostly male (73.7%)) were interviewed. Initial rhythm was shockable in 210 (82.4%) cases. Global physical and mental components did not differ between OHCA survivors and general population (47.0 vs. 47.1, p=0.88 and 46.4 vs. 46.9, p=0.45). However, physical functioning and vitality were significantly altered in OHCA survivors (Figure. SF-36 dimensions of 255 OHCA patients (grey rectangles) and of matched controls (black circles)). Younger age and male gender were independently associated with almost all SF-36 dimensions. Initial VF/VT was associated with a gain in most of the SF-36 dimensions. Successful PCI was associated with a gain in physical functioning (+7.0, p=0.06) and in general health (+7.3, p=0.02) and in vitality (+4.4, p=0.08).

Conclusions:
HRQOL of OHCA survivors appears similar to general population, but some physical components of SF36 scale were significantly altered. Younger age, male gender, initial shockable rhythm and coronary reperfusion were independently associated with a better HRQOL.
Abstract 14261: Molecular Basis of the Protective Effect of β3-Adrenergic Receptor Deficiency on Myocardial Aging: Reversal of Aging-Induced Contrast Changes of Cardiac SERCA 2a and Inducible Nitric Oxide Synthase
Authors: Cheng Heng-Jie , Zhou Peng , Li Tiankai , Zhang Xiaowei , Masutani Satoshi , Kitzman Dalane , Little William , Cheng Che Ping
Published: April 2024

Background:
We have shown previously that aging-induced cardiac dysfunction and β-adrenergic desensitization were prevented in β
3
-adrenergic receptor (AR) knockout (β
3
KO) aged mice. However, the molecular mechanism is unclear. We hypothesize that reversal of aging-induced alterations of cardiac SR Ca
2+
-ATPase (SERCA2a) and inducible nitric oxide synthase (iNOS) by β
3
KO may play a key role for the protective effect.

Methods:
We compared protein levels of β
1
- and β
3
-AR, SERCA2a and iNOS, myocyte contractile, [Ca
2+
]
i
transient ([Ca
2+
]
iT
) and Ca current (I
Ca,L
) responses to isoproterenol (ISO, 10
-8
M) in LV myocytes obtained from 2 young (Y) (~6 m) and 2 aged (A) (~28 m) groups (6/group) of wild-type (WT) and β
3
KO mice, respectively.

Results:
Compared with YWT, AWT myocytes had significantly decreased protein levels of SERCA2a (AWT: 0.23 vs YWT: 0.64), and β
1
-AR (0.33 vs 0.58), but increased iNOS (0.50 vs 0.23) and β
3
-AR (0.34 vs 0.15) with reduced basal cell contraction (dL/dt
max
) (84.5 vs 126.4 μm/s), relaxation (dR/dt
max
) (66.9 vs 101.8 μm/s), [Ca
2+
]
iT
(0.18 vs 0.24), and I
Ca,L
(4.4 vs 7.7 pA/pF). These changes were accompanied by diminished ISO-stimulated inotropic response. In AWT myocytes, ISO caused significantly less increases in dL/dt
max
(AWT: 33% vs YWT: 80%), dR/dt
max
(24% vs 62%), [Ca
2+
]
iT
(16% vs 37%) and I
Ca,L
(15% vs 33%). Versus YWT, Yβ
3
KO did not alter basal myocyte contraction and relaxation and response to ISO stimulation, but had significantly increased protein levels of SERCA2a (Yβ
3
KO: 1.40 vs YWT: 0.62) and reduced iNOS (0.18 vs 0.26) with unchanged β
1
-AR (0.65 vs 0.62). Aβ
3
KO mice had similar alterations. Importantly, in contrast to AWT, in Aβ
3
KO myocytes, the increased SERCA2a (1.2) and reduced iNOS (0.16) correlated with normal basal cell contraction and relaxation with preserved ISO-stimulated inotropic response. ISO caused similar increases in dL/dt
max
(Aβ
3
KO: 80% vs Yβ
3
KO: 83%), dR/dt
max
(68% vs 61%), [Ca
2+
]
iT
(30% vs 32%) and I
Ca,L
(29% vs 31%).

Conclusions:
β
3
KO prevents aging-caused downregulation of cardiac β
1
-ARs and reverses increased iNOS and decreased SERCA2a, leading to the preservation of myocyte function, [Ca
2+
]
iT
, I
Ca,L
and β-adrenergic reserve in aged hearts. Thus, β
3
-AR may provide a new target for cardiac aging.
Abstract 14300: Agonal Respiration With and Without Carotid Pulsation on Emergency Medical Technician’s Arrival at Patient
Authors: Inaba Hideo , Takei Yutaka , Kamikura Takahisa , Funada Akira , Wato Yukihiro , Sakagami Satoru , Myojo Yasuhiro
Published: April 2024

Aim:
To determine the association between agonal respirations with and without carotid pulsation and neurologically favorable one-year survival from OHCAs.

Methods and Results:
Data for resuscitation-attempted, 7,048 OHCAs were prospectively collected during the period of 2007-2013 in Ishikawa Prefecture. Of these, 6,600 cases were in deep coma, and had agonal respiration (N = 238) or no respiration (N = 6,362). Carotid pulse was present in 26 (10.9%) of 238 cases with agonal respiration, and in 34 (0.5%) of 6,382 cases with no respiration (respiratory arrest cases in the narrow sense). The rate of neurologically favorable one-year survival in the agonal respiration with pulse, agonal respiration without pulse, no respiration with pulse, no respiration without pulse groups was 15.4% (4/26), 21.7% (46/212), 14.7% (5/34), and 2.3% (143/6328), respectively. Interaction test for survival disclosed a significant interaction between respiration and pulsation (p = 0.002). Agonal breathing was strongly associated with shockable initial rhythm (OR; 95% CI, 3.73; 2.66-5.23) and neurologically favorable one-year survival (12.0; 8.3-17.3) only when pulse was absent on EMT arrival at patients (Table). The survival rate was extremely high [56.3% (27/48)] when initial rhythm was shockable and when agonal respiration was observed.

Conclusions:
Carotid pulse was present in some (11%) of OHCA patients with agonal respiration on ENT arrival at patients, indicating that chest compressions may be initiated before “true” cardiac arrest in adherence to current BLS guidelines. Agonal respiration was associated with neurologically favorable survival from OHCAs only when carotid pulse was absent on EMT arrival at patients.
Abstract 14308: Parameters of Exercise Stress Testing Are Associated With Incident Major Cardiovascular Event independent of Risk Factors and Coronary Artery Calcification - The Heinz Nixdorf Recall Study
Authors: Mahabadi Amir A , Lehmann Nils , Kälsch Hagen , Pundt Noreen , Dykun Iryna , Moebus Susanne , Jöckel Karl-Heinz , Erbel Raimund , Möhlenkamp Stefan
Published: April 2024

Objective:
To assess the prognostic value of parameters of autonomic cardiac function and cardiovascular fitness, as derived from exercise stress ECG testing, in addition to traditional risk factors and the anatomic information of coronary artery calcification (CAC)-score.

Methods:
Participants from the population based Heinz Nixdorf Recall Study without known cardiovascular disease and without heart rate lowering therapy were included. CAC-score was quantified from non-contrast electron beam CT. From bicycle stress ECG testing peak heart rate (HR), HR recovery (decline of HR 1 minute after peak exercise), exercise capacity, exercise duration, and chronotropic incompetence (chronotropic response of ≤80%) were assessed. We determined gender differences of exercise parameters. Associations with cardiovascular events (myocardial infarction, stroke, cardiovascular death) were evaluated using multivariable Cox regression.

Results:
We included 2349 subjects (age 58.1 ± 7.4 years, 48% male). Exercise duration and exercise capacity were higher in men (11.6 ± 3.0 vs. 7.6 ± 1.9 min, p<0.0001 and 8.9 ± 1.9 vs. 6.5 ± 1.3 METs, p<0.0001), while peak HR, HR recovery, and frequency of chronotropic response were not significantly different between gender (p>0.05). During a median (Q1; Q3) follow-up of 10.6 (10.2; 11.4) years, 118 cardiovascular events occurred. Adjusting for Framingham risk score, peak HR (0.70 (0.52-0.95), p=0.02), HR recovery (0.70 (0.50-0.98), p=0.04), exercise capacity (0.64 (0.45-0.92), p=0.01), and chronotopic incompetence (2.62 (1.35-5.06), p=0.004) were associated with events in women, while only exercise duration was significantly associated in men (0.77 (0.60-0.99), p=0.04). When ancillary adjusting for CAC-score, exercise duration was associated with events in both genders (women: 0.67 (0.47-0.96), p=0.03, men: 0.61 (0.43-0.87), p=0.007), while chronotropic incompetence (2.43 (1.25-4.70), p=0.01) and exercise capacity (0.69 (0.48-0.99), p=0.04) were significantly associated in women only.

Conclusion:
Parameters of exercise stress ECG testing are associated with incident major cardiovascular events, independent of traditional risk factors and coronary artery calcification, especially in female subjects.
Abstract 14344: The Magnitude and Time Course of Stress Induced Left Ventricular Transient Ischemic Dilation: A CMR Perspective
Authors: Lisko John C , Morgenstern Daniel , Nicoloff Nicola , Mikolich Brandon , Mikolich J. Ronald
Published: April 2024

Background:
Transient ischemic dilation (TID) of the left ventricle is used in nuclear myocardial stress perfusion imaging to identify global myocardial ischemia due to multi-vessel atherosclerosis. Although the isotope is injected at peak stress, nuclear stress images are obtained 20-30 minutes later to allow for hepatic clearance of isotope. Cardiac MRI myocardial stress perfusion imaging is performed at peak regadenoson effect. Given the superior spatial resolution of CMR, it also useful for accurate assessment of LV dimensions, both at rest and after stress. This prospective study was designed to assess the time course of peak regadenoson TID with direct measurement of LV dimensions and volumes using CMR.

Methods:
A standard CMR myocardial perfusion protocol was modified by adding a short axis SSFP imaging sequence at the level of the papillary muscle tips, just before the 1st pass perfusion study at peak regadenoson effect, and again 20-30 minutes later, after delayed enhancement imaging was completed. Parameters for this study included LV end-diastolic diameter (EDD) and slice volume (EDV), LV end-systolic diameter (ESD) and slice volume (ESV). TID was defined as an increase in end-diastolic diameter at stress compared to rest. An independent sample t-test was used to compare mean values.

Results:
Data was obtained from 181 consecutive patients undergoing CMR stress studies over a 6 month period. Stress induced LV dilation occurred in 61 patients, but not in 120. Of 61 patients with stress induced LV dilation, the mean slice EDV at rest was 18.24 mL3 and increased to 19.83 mL3 at stress (p<.05). At 20-30 minutes post regadenoson, mean slice volume remained non-significantly elevated at 18.84mL3 (p=.415) relative to the baseline slice EDV. Of the 120 patients without stress induced dilation, mean slice EDV decreased from 21.10 mL3 at rest to 19.65 mL3 at stress (p<.05). Mean slice volume remained non-significantly decreased at 20-30 minutes post stress (p=.188).

Conclusions:
These data suggest that maximum TID occurs at the time of peak regadenoson effect and attenuates to baseline over 20-30 minutes. Because of the inherent delay in obtaining myocardial stress perfusion images with a nuclear technique, CMR stress assessment of TID may be preferable.
Abstract 14567: Detection of Acute Cellular Rejection in Pediatric Heart Transplantation: A Pilot Cardiac Magnetic Resonance Imaging Study
Authors: Greenway Steven C , Dallaire Frederic , Kantor Paul F , Dipchand Anne I , Chaturvedi Rajiv R , Warade Monali , Riesenkampff Eugenie , Yoo Shi-Joon , Grosse-Wortmann Lars
Published: April 2024

Introduction:
The diagnosis of significant acute cellular rejection (ACR) after heart transplantation (HT) prompts an immediate change in management and is associated with adverse outcome. Endomyocardial biopsy (EMB) is the gold standard for the detection of ACR but has important limitations. The purpose of this study was to evaluate cardiac magnetic resonance imaging (CMR) as a non-invasive tool to detect ACR in pediatric patients after HT.

Methods:
In this single centre prospective cohort study, 30 pediatric HT recipients underwent CMR at the time of surveillance EMB. Their CMR results were compared to 14 non-HT pediatric controls. Ventricular volumes and ejection fraction, native T1 times and T2-weighted signal intensities were compared between patients and controls and between patients with (grade 2 R) and without (grade 0 R/1 R) significant ACR according to standard criteria. Extracellular volumes (ECV) and the presence of late gadolinium enhancement (LGE) were compared between the two HT groups.

Results:
There were no significant demographic differences between the patient groups. Transplant patients were on average 11 ± 6.1 years of age and were 31.5 ± 41.3 months post-transplant. Significant (grade 2 R) ACR was an infrequent event in our population (5/30, 17%). Compared to controls, heart rate (100.3 ± 16.4 bpm) and brain natriuretic peptide (60.8 ± 100.7 ng/L) were significantly elevated post-HT but did not differentiate between grades of ACR. Ventricular volumes, ejection fractions, LGE prevalence, ECVs, native T1 times and T2 signal intensities were not significantly altered by ACR.

Conclusions:
We describe the myocardial characteristics of pediatric HT recipients by CMR. Although limited by the small number of patients with significant ACR the results of this pilot study suggest that current CMR imaging protocols are insufficient to reliably identify ACR-related changes in pediatric HT.
Abstract 14586: Total Scar Burden Predicts Cardiac Resynchronization Therapy (CRT) Response Beyond Left Bundle Branch Block (LBBB) and QRS Duration (QRSd) and Regardless of the Type of Cardiomyopathy (CM)
Authors: Harb Serge C , Chareonsri Nisarat , Popovic Zoran , Wahaj Aman , Varma Niraj , Flamm Scott , Kwon Deborah
Published: April 2024

Introduction:
Prior studies have demonstrated that up to 30% of patients do not benefit from CRT and that response may be affected by the extent and location of myocardial scar. We sought to determine the predictive value of the scar burden on CRT response after controlling for the type of cardiomyopathy (Ischemic=ICM vs. Non-Ischemic=NICM), the presence of LBBB and QRSd.

Methods:
We reviewed 71 pts (49% NICM, age 71 +/- 11, 34% women) who underwent cardiac MRI (CMR) pre-CRT. Total and lateral wall % scar were measured and pre-CRT ECG features (LBBB and QRSd) were noted. The change in EF on echo >6 months post-CRT was calculated and a positive response was defined as a ≥10% increase in left ventricular ejection fraction (EF). The relationship between LBBB, QRSd, total and lateral scar % and change in EF were investigated using Pearson (r) correlation. Hierarchical multiple regression was used to assess the ability of total and lateral scar burden to predict CRT response after controlling for the type of CM, the presence of LBBB and QRSd.

Results:
Mean EF pre-CRT was 23.6%+/-8 and correlated significantly with EF by CMR (mean =24.4 +/-10; r = 0.5, p<0.01). LBBB was present in 52% of pts and mean QRSd was 152ms. A positive response to CRT was noted in 52% of pts. The change in EF correlated significantly with the presence of LBBB (0.31; p=0.01), QRSd (0.27; p=0.03); total scar % (-0.39; p<0.01) and lateral scar % (-0.28;p=0.02). After controlling for the type of CM, and presence of LBBB and QRSd, total scar % was still significantly predictive of the response to CRT [R squared change (tot scar) = 0.06, F change (1,63) = 16, p=0.01] - see table 1. With lateral scar, the same analysis was not significant [R squared change (lat scar)=0.04, F change (1,62)=3.5 p=0.06]

Conclusion:
Assessment of total scar burden provides incremental predictive value to CRT response after controlling for the type of CM (ICM vs. NICM), the presence of LBBB and QRSd.
Abstract 14688: Paradox of Right Ventricular Function: Lower the Better? -- Right Ventricular Dysfunction May Predict the Diagnosis of Tachycardia Induced Cardiomyopathy
Authors: Okada Atsushi , Nakajima Ikutaro , Morita Yoshiaki , Kamakura Tsukasa , Wada Mitsuru , Ishibashi Kohei , Miyamoto Koji , Nagase Satoshi , Noda Takashi , Aiba Takeshi , Kamakura Shiro , Anzai Toshihisa , Noguchi Teruo , Yasuda Satoshi , Ogawa Hisao , Kusano Kengo F
Published: April 2024

Background:
Differentiating tachycardia induced cardiomyopathy (TIC) from other dilated cardiomyopathies (DCM) remains challenging in patients presenting with LV dysfunction and AF tachycardia. While sustained rapid pacing in animals produces biventricular dysfunction, left-sided heart failure patients develop right ventricular (RV) dysfunction in advanced stages following increase in pulmonary vascular resistance. We hypothesized that RV dysfunction at presentation may predict the diagnosis of TIC.

Methods:
We studied the RV function using CMR in 102 consecutive patients with LVEF<45% and uncontrolled AF tachycardia (defined as heart rate over 100 at rest or over 160 on exercise). Patients with coronary, valvular, congenital, or other secondary cardiomyopathies were not included. CMR was performed after heart rate stabilization, and ventricular functions assessed by Argus (Siemens, Germany), endomyocardial biopsies and hemodynamic data from Swan-Ganz catheter were analyzed. Patients who had normal EF after 1 year treatment were classified as TIC group (n=45), and patients who did not as DCM group (n=57).

Results:
LVEF at presentation by echocardiogram were similar between the 2 groups (29.2±9.7 vs.28.1±8.0%, p=0.79). At CMR, TIC group had higher LVEF (33.5±9.8 vs. 24.8±7.6%, p<0.001) but tended to have lower RVEF (33.0±7.4 vs. 35.0±6.7%, p=0.11). No significant differences were observed between TIC and DCM in myocardial fibrosis, hypertrophy or hemodynamic parameters including pulmonary vascular resistance. RVEF/LVEF ratio was significantly lower in TIC (1.03±0.25 vs. 1.51±0.45, p<0.001), and by ROC analysis, RVEF/LVEF ratio<1.1 predicted TIC with a sensitivity of 76% and specificity of 87% (AUC=0.85). Logistic regression analysis showed RVEF/LVEF ratio is a strong independent predictor of TIC (OR=0.62 per 0.1, p<0.001).

Conclusions:
RV dysfunction assessed by RVEF/LVEF ratio was highly predictive of TIC. Ventricular impairment in TIC occurs equally in both ventricles, and RV dysfunction in TIC develops without elevation of pulmonary vascular resistance. While RV dysfunction generally indicates advanced heart failure with worse prognosis, it may also indicate TIC, which is generally considered to have good prognosis.
Abstract 14692: Evaluation of Subaortic Right Ventricular Function in ccTGA: How Do Echocardiography Parameters Compare to CMR?
Authors: Albinmousa Zakariya , Kha Lan-Chau , Carlo Alessia D , Wong Alton , Crean Andrew , Wald Rachel , Wilson William , Roche Lucy S
Published: April 2024

Background:
Subaortic right ventricular (RV) functional assessment in patients with congenitally corrected transposition of the great arteries (ccTGA) is important for both long-term outcome and as an indication for tricuspid valve replacement. Cardiac magnetic resonance (CMR) imaging is considered the reference standard for assessment of subaortic RV systolic function. However, two-dimensional echocardiography (2DE) remains the most frequently used imaging modality in clinical practice.

Objective:
To compare 2DE and CMR parameters of RV function in patients with ccTGA.

Methods:
We identified adults (≥18) with the diagnosis of ccTGA who underwent consecutive CMR and 2DE imaging within 6 months between 2005 and 2015. Patients with tricuspid valve replacement or pacemaker were excluded. 2DE images were reviewed and the following RV parameters re-measured by a single observer: fractional area shortening (FAC), tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (Ts’), the rate of systolic RV pressure increase (dp/dt) and myocardial acceleration during isovolumic contraction (IVA). RVEF as measured by CMR was recorded.

Results:
There were 82 matched 2DE and CMR studies in 42 ccTGA patients (50% male). Median age at 2DE was 33.1 years (IQR = 22.7- 48.2 year). Pearson correlation analysis demonstrated a weak correlation between FAC and RVEF (r
2
=0.143, p=0.0005). Other 2DE parameters failed to show any correlation with RVEF (Figure 1).

Conclusion:
In general, 2DE parameters for the assessment of subaortic RV systolic function correlate poorly with CMR measured RVEF in patients with ccTGA. This is important information for selection and interpretation of various modalities in the long-term follow-up of this patient population.
Abstract 14694: Ventricular Fibroblasts Expression of Orai1 and Ca2+ -influx Through ICRAC is Increased in Human Heart Failure
Authors: Ross Gracious R. , Bajwa Tanvir , Kraft Kelsey , Cosic Milanka , Emelyanova Larisa , Rizvi Farhan , Holmuhamedov Ekhson L. , Werner Paul , Tajik A. Jamil , Jahangir Arshad
Published: April 2024

Introduction:
Increased ventricular fibrosis contributes to the progression of heart failure (HF); interventions that limit fibrosis are proposed to improve cardiovascular outcomes. Intracellular Ca2+-dependent processes like excessive fibroblast (FB) proliferation, activation and secretion of extracellular matrix and cytokines are critical for progression of fibrosis. Defining pathways that increase Ca2+ mobilization in FB from HF patients could identify a novel target to prevent fibrosis and HF progression.

Hypothesis:
We hypothesized that human ventricular FB (hVF) from a failing heart will have enhanced intracellular Ca2+ release and ICRAC (Ca2+-release activated channel)-mediated Ca2+ influx.

Methods:
Primary cultures of hVF obtained from HF patients undergoing left ventricular assist device implantation (n = 9) were compared to non-diseased hVF from trauma victims (n = 3). Cytosolic free Ca2+ imaging was performed in FB preloaded with fluo-3 AM (confocal microscopy) and thapsigargin (2.5 μM) was used to release and deplete intracellular Ca2+ stores in Ca2+-free KRH solution followed by addition of CaCl2 (2 mM) to assess Ca2+ influx (ICRAC). Ionomycin (2 μM) was used for normalization. Protein expression of STIM1, Orai1 and GAPDH was performed by immunoblotting. Data were analyzed by unpaired Student’s t-test.

Results:
Ca2+ release from intracellular stores by thapsigargin was not different (p = 0.7) between control (16 ± 1%) and HF groups (15 ± 1%), but store-operated Ca2+-influx (ICRAC) was significantly (p = 0.05) elevated in HF (43 ± 2%) compared to control group (32 ± 5%). The Ca2+-influx was sensitive to YM-58483 (10 μM), an ICRAC inhibitor (9 ± 2%, n = 4, p <0.01). Immunoblots of the components of ICRAC channel, STIM1 and Orai1, showed significant (p = 0.01) increase in the Orai1 expression in HF group (0.09 ± 0.01 AU, n = 8) compared to control (0.04 ± 0.01 AU, n = 3) but no difference (p = 0.7) in STIM1 expression (control [0.19 ± 0.02 AU, n = 3] vs HF [0.2 ± 0.02 AU, n = 8]).

Conclusions:
Store-operated Ca2+ influx is significantly increased in hVF from HF patients and may play an important role in the progression of cardiac fibrosis. Selective fibroblast Orai1 inhibition may be a potential therapeutic target to prevent progressive worsening of HF.
Abstract 14717: Identifying Predictors of Red Cell Distribution Width at Admission and Changes in RDW During Heart Failure Hospitalization
Authors: Horne Benjamin D , Muhlestein Joseph B , Budge Deborah , Lappé Donald L , Muhlestein Joseph B , Bennett Sterling T , Benuzillo José , Bradshaw Alejandra , May Heidi T , Bair Tami L , Anderson Jeffrey L
Published: April 2024

Introduction:
The causes of risk-associated elevations in red cell distribution width (RDW) are unknown, but RDW strongly predicts adverse outcomes in heart failure (HF) patients. Initial RDW level and the change in RDW (ΔRDW) were previously shown to predict hospital length of stay, 30-day readmission, and 30-day mortality.

Hypothesis:
Risk factors and diagnoses predict initial RDW and in-hospital ΔRDW of HF patients.

Methods:
Patients (N=6,414) were studied if they had an inpatient stay for the primary diagnosis of HF during 2004-2013, had RDW measured within 24 hours after admission, and had a second RDW tested within 24 hours prior to discharge. ΔRDW was calculated as the difference between the two RDW measurements. All patients were aged 65 years or older and were discharged alive and not to hospice.

Results:
In linear regression, predictors of initial RDW included age, being ever diagnosed with 15 comorbidities (Table), and diagnosis in the prior month with 8 comorbidities. Those 24 factors explained 10.5% of the variation in RDW (model F-statistic= 33.3, p<0.001). In contrast, predictors of ΔRDW were sex, length of stay, initial red blood cell count, mean corpuscular volume, RDW, mean corpuscular hemoglobin concentration, sodium, calcium, potassium, medications administered in-hospital (e.g., ACE-I, inotropes, and vasopressors), and diagnosis ever or within the last month of various comorbidities (Table). Those factors explained 13.9% of the variation in ΔRDW (model F-statistic= 35.9, p<0.001).

Conclusions:
Predictors of initial RDW and ΔRDW in HF patients clustered among diagnoses of cardiovascular, pulmonary, renal, and psychological diseases, and (as expected) hematological/bleeding conditions. These findings may aid in determining the cause of RDW elevations and in personalizing medical care using common, inexpensive, electronic laboratory data. With most variance in RDW and ΔRDW still unexplained, discovery of other predictors is needed.
Abstract 14728: Atrial Fibrillation After Orthotopic Heart Transplantation: Results From a Meta-analysis
Authors: Metz Tamara , Mohanty Sanghamitra , Mohanty Prasant , Trivedi Chintan , Gianni Carola , Di Biase Luigi , Natale Andrea
Published: April 2024

Background:
Atrial fibrillation (AF) is a known complication of orthotopic heart transplantation (OHT). However, post-OHT AF is yet to be well characterized as studies report diverse data on the incidence rate and clinical characteristics of this arrhythmia. This study provides a review and meta-analysis of the existing evidences on the incidence rate, time of onset and association with allograft rejection of post-OHT AF.

Methods:
An extensive literature search was performed on PubMed, MEDLINE and EMBASE databases (from 1990 to August 2014) and reference lists of selected articles for studies on the incidence of atrial fibrillation in OHT patients. Post OHT arrhythmia incidence data along with population characteristics were collected and pooled prevalence rate and associated 95% confidence intervals (CIs) were calculated.

Results:
Ten prospective studies with 3,852 patients undergoing OHT were included in the primary meta-analysis. The pooled prevalence of AF across studies was 5.4% (95% CI 7.0-10.1). AF was the most common early arrhythmia; 74% (95% CI 65-83) of the reported AF episodes were observed in <30 days of OHT. The pooled prevalence of AF was much higher with allograft rejection (41.5%, 95% CI 32-52, p<0.001). Additionally, two studies reported lower incidence of AF following OHT compared to the AF-incidence after other cardiac surgeries such as MAZE and double- lung transplantation, despite pulmonary vein isolation in both groups (relative OR 0.25, 95% CI 0.07-0.56), which they attributed to the antiarrhythmic benefit of cardiac denervation in the transplanted heart.

Conclusion:
In heart transplant recipients atrial fibrillation is uncommon; mostly seen in the early post-operative period and often in the presence of graft rejection. Of note, cardiac autonomic denervation may have a protective antiarrhythmic effect in the post-operative setting of orthotopic heart transplantation.
Abstract 14743: Intracellular Adenosine Suppresses Vsmc Phenotypic Switch Through Klf4 Gene Methylation
Authors: Wang Yong , Xu Yiming , Zeng Xianqiu , Zhou Yaqi , Liu Zhiping , Wu Chaodong , Li Qinkai , Huo Yuqing
Published: April 2024

Background and objective:
It is well known that adenosine affects the growth of vascular smooth muscle cells via adenosine receptors. Adenosine kinase (ADK) is an intracellular enzyme regulating the levels of adenosine in intracellular and further extracellular compartments. The effect of ADK on VSMC phenotypic switch is unknown. In this study, we evaluate phenotypic changes of VSCMs both in vitro and in vivo following deletion of ADK in VSMCs.

Methods and results:
The expression of ADK in vascular wall was significant upregulated in mouse carotid artery ligation model. Heterogeneous deletion of ADK or specific ADK deletion in VSMCs led to remarkably decreased neointima in ligated mouse carotid arteries (Fig. A&B). This was accompanied with increased expression of VSMC differentiation markers and transcriptional factor KLF4 (Fig. D). In an in vitro setup, treatment of VSMCs with ADK shRNA or ADK inhibitors suppressed serum or PDGF-induced SMC proliferation and migration (Fig. C). This effect remained intact in the presence of adenosine receptor antagonists to A1, A2A, A2B and A3. Deletion of ADK in VSMCs increased the levels of intracellular adenosine, decreased the methylation levels of genes and histones, and augmented KLF4 expression. It is being investigated that upregulation of KLF4 was resulted from its gene hypomethylation in response to elevated intracellular adenosine following ADK deletion/knockdown or inhibition.

Conclusions:
Our data demonstrate that ADK deletion/inhibition suppresses neointima formation in injured arteries through a novel epigenetic pathway but not classic adenosine receptors, and ADK is a promising therapeutic target in the treatment of arterial diseases such as atherosclerosis and arterial neointima formation following arterial angioplasty.
Abstract 14763: Discontinuation of Dofetilide or Qt Prolongation is Much More Common in Real-world Setting Than Reported in Clinical Trials
Authors: Anand Vidhu , Vakil Kairav , Adabag Selcuk
Published: April 2024

Introduction:
Dofetilide is a class III anti-arrhythmic agent approved for achieving and maintaining sinus rhythm in patients with symptomatic atrial fibrillation or flutter (AF). Due to a risk of QT prolongation and ventricular tachycardia (VT) patients initiated on Dofetilide need to be hospitalized for at least 3 days to closely monitor ECG. In large clinical trials 1.8-2.5% of the patients had to discontinue Dofetilide due to QT prolongation. We aimed to evaluate the frequency and correlates of discontinuation of Dofetilide due to QT prolongation (QTc >500 msec) or VT in a real-world, inpatient setting.

Methods:
We included 100 consecutive patients, hospitalized for Dofetilide initiation at the Minneapolis VA Medical Center from 2011 to 2014. Data was collected retrospectively from electronic medical records.

Results:
The mean age was 63.8 ± 9.1 years. The indication for Dofetilide was AF (88%) and VT (12%). Dofetilide had to be discontinued in 21% of the patients due to QTc prolongation (17%) or VT (2%) or lack of efficacy (2%). One patient died in the hospital. The mean QTc in patients in whom Dofetilide had to be discontinued was 512±53 msec. In 29% of the cases Dofetilide cardioverted patients to sinus rhythm. Patients who had to discontinue Dofetilide were less likely to have coronary heart disease (CHD) than those who were discharged on Dofetilide (14% vs. 44%, respectively; p= 0.012) (Table). The average number of doses received by patients before discharge was 5.5±0.9 in patients who were discharged on Dofetilde vs. 3.2±1.5 in whom Dofetilide was discontinued because of QTc prolongation (55% discontinued after 2
nd
dose). Concomitant

QTc prolonging drugs were used in 29% of patients who had to discontinue Dofetilide vs. 24% of those who were discharged on Dofetilide (p=0.78) (Table).

Conclusion:
The incidence of Dofetilide discontinuation due to high-risk ECG features in the real world setting is remarkably higher than that reported in prior clinical trials.
Abstract 14805: Use of Dedicated Protocol and Implantable Loop Recorder to Evaluate for Atrial Fibrillation in Cryptogenic Stroke Patients: Real World Validation of Crystal AF
Authors: Seiler Amber , Biby Sharon , Sethi Pramod , Allred James
Published: April 2024

Introduction:
Embolic strokes related to atrial fibrillation (AF) carry significant morbidity and mortality. Identifying patients with asymptomatic AF following stroke is difficult. A protocol for incorporation of implantable loop recorders (ILR) in stroke management has not been established.

Methods:
We developed a protocol for evaluation of patients with cryptogenic embolic stroke using ILR for detection of AF (figure 1). Patients implanted with ILR were enrolled in an AF clinic with structured remote follow-up. The primary end point was time to first detected AF. Secondary end point was time to initiation of anticoagulation following identification of AF.

Results:
95 patients underwent ILR placement. Baseline characteristics are shown in table 1.

The median time between stroke and ILR placement was 6 days with a range of 1 to 496 days. The mean follow-up time was 169.4 +/- 103.1days. 18 patients (18.9%) had AF detected during the study period (Figure 2). Mean time to detection of AF was 95.7 +/- 93.6 days. 94.4% were anticoagulated (52.9% Rivaroxaban, 41.2% Apixaban, 5.9% Warfarin). The median time from detection of AF to initiation of anticoagulation was 2 days with a range of 1 to 28 days.

Conclusions:
A protocol for incorporating ILR in evaluation of embolic cryptogenic stroke can improve AF detection and time to initiation of anticoagulation.
Abstract 14839: Association of Silent Brain Infarction With CHADS2 Score and Left Atrial Abnormalities in Patients With Nonvalvular Atrial Fibrillation
Authors: Kawai Yu , Sugioka Kenichi , Iwata Shinichi , Fujita Suwako , Ito Asahiro , Matsumura Yoshiki , Hanatani Akihisa , Takagi Masahiko , Yoshiyama Minoru
Published: April 2024

Introduction:
The CHADS2 score is widely used for risk stratification of thromboembolism in patients with nonvalvular atrial fibrillation (NVAF). Furthermore, LA abnormalities detected by transesophageal echocardiography (TEE) are also well known risk factors for thromboembolism in NVAF patients. On the other hand, silent brain infarction (SBI) relates to subsequent symptomatic brain infarction; however little is known regarding association among CHADS2 score, TEE parameters and SBI.

Methods:
The study population consisted of 103 neurologically asymptomatic patients with NVAF (mean age 63 ± 10 years) who underwent TEE. All participating patients underwent brain MRI and were calculated CHADS2 score. SBI was defined as an area of hypointense lesions that measured >3 mm on T1-weighted images and hyperintense lesions on T2-weighted images by brain magnetic resonance imaging (MRI). LA abnormalities were defined as LA thrombus, spontaneous echo contrast, or low LA appendage emptying velocity (<20 cm/s) detected by TEE.

Results:
Of 103 patients, 31 (30%) showed SBI on brain MRI. Over all mean CHADS2 score was 1.1 ± 0.9, and LA abnormalities were detected in 24 patients by TEE (23%). Mean CHADS2 score in patients with SBI was significantly higher than that in patients without SBI (P<0.05). The prevalence of SBI increased along with increases in CHADS2 score (CHADS2 score of 0, 1, 2 and 3-6 in 13%, 23%, 47% and 80%, respectively, P<0.05). Patients with SBI had a higher prevalence of LA abnormalities than those without SBI (P<0.05). In patients with SBI with CHADS2 score of 0-1, LA abnormalities were detected in 5 of 14 patients (36%).

Conclusions:
In this study, both CHADS2 score and prevalence of LA abnormalities by TEE were higher in patients with SBI on MRI. LA abnormalities detected by TEE may discriminate risk for SBI even in patients with low CHADS2 score.
Abstract 14879: Comparing the Risk of Heart Failure Among Different Dipeptidyl Peptidase 4 Inhibitors
Authors: Lin Jou Wei , Chang Chia-Hsuin , Lai Mei-Shu
Published: April 2024

Introduction:
Dipeptidyl peptidase 4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes mellitus by increasing incretin levels, inhibiting glucagon release, and augmenting insulin secretion. Previous trials raised safety concerns regarding a potential risk of hospitalization for heart failure (HF), but the most recent TECOS trial suggests that adding sitagliptin to usual care did not increase the risk. The objective of this study was to compare the risk of hospitalization for HF among different types of DDP-4 inhibitors.

Methods:
Diabetic patients who started to use sitagliptin, saxagliptin, and vildagliptin between 2011 and 2013 were identified from Taiwan's National Health Insurance (NHI) claims database. The outcome of interest was the first hospitalization due to HF (ICD-9-CM cod 428). The patients were followed from drug initiation to the outcome occurrence, death or disenrollment from NHI, one year after treatment initiation, or study termination (December 31, 2013). A Cox proportional hazards regression model adjusted for baseline characteristics was used to calculate the hazard ratios (HR) and their 95% confidence intervals, using sitagliptin as the reference group.

Results:
A total of 239,669 patients, including 159,330 sitagliptin, 38,561 saxagliptin, and 41,778 vildagliptin initiators, were included in the analysis. The mean age of 62.2 years and 52% were male. With a follow-up period ranging from 269 days (vildagliptin) to 313 days (sitagliptin), the crude incidence rate of HF was 2.77, 2.63, and 1.91 per 100 person-years for sitagliptin, saxagliptin, and vildagliptin, respectively. Saxagliptin had a similar HF risk (HR: 0.98, 95% CI: 0.91-1.06) compared to sitagliptin while vildagliptin was associated with a lower risk of HF (HR: 0.85, 95% CI: 0.78-0.93).

Conclusions:
The safety profile was not all the same among different types of DPP-4 inhibitors in diabetic patients. Vildagliptin was associated with a lower risk of HF than sitagliptin and saxagliptin.
Abstract 14896: Does Echocardiography/Doppler Reliably Predict Elevated LVEDP?
Authors: Cameron David M , Bach David , McLaughlin Vallerie , Rubenfire Melvyn , Visovatti Scott
Published: April 2024

Introduction:
Heart failure with preserved ejection fraction is a common cause of group 2 pulmonary hypertension (PH). The utility of echocardiography (echo)/ Doppler for identification of elevated left ventricular end-diastolic pressure (LVEDP) specifically among patients with PH is not well defined.

Methods:
161 patients referred to Pulmonary Hypertension Clinic were retrospectively studied. Included patients underwent echo/Doppler and had catheter measurement of LVEDP or pulmonary capillary wedge pressure within a 3-month period, had normal sinus rhythm at the time of the TTE, and had unchanged diuretic and PH regimens during the examination interval. The ability of echo to predict elevated LVEDP (> 15 mm Hg) based on American Society of Echocardiography (ASE) / European Association of Echocardiography (EAE) guidelines was evaluated, and a new model was developed for better prediction of elevated LVEDP with echo data using univariate linear regression and multi-variable logistic regression; receiver operating characteristics were analyzed.

Results:
Of 161 patients, 81 (51%) had LVEDP > 15 mm Hg on invasive testing; mean PAP was 37.8 ± 14.3 mmHg and PVR was 4.6 ±3.8 WU. Doppler E/A, E/e’ (septal, lateral, average), e’/a’ (lateral and average), LA volume, and LA diameter had significant correlation with LVEDP (p values < 0.05). There was poor test performance of both the ASE/EAE model and the experimental model (area under the ROC 0.7, p < 0.001). Only echo/Doppler grade III had a mean LVEDP significantly different from other grades (p value < 0.05).

Conclusions:
Numerous echo/Doppler measurements correlate with elevated LV filling pressure. However, both the ASE/EAE model and our experimental model had poor test performance that did not permit confident identification of patients with elevated LVEDP. Assessment using echo/Doppler is not adequate to either reliably include or exclude patients with elevated LVEDP as a cause of severe PH.
Abstract 14910: Vascular Cells Originating From Perivascular Adipose Tissue Contribute to Vasa Vasorum Neovascularization in Atherosclerosis
Authors: Tanaka Kimie , Komuro Issei , Sata Masataka
Published: April 2024

Introduction:
Proliferation of vasa vasorum (VV) is observed in the adventitia of arteries with atherosclerotic plaques. It was reported that fat tissue transplantation to carotid artery exaggerated neointimal formation and VV proliferation after wire injury in a hypercholesterolemic mouse model. However, there is no in vivo histological evidence that vascular cells originating from perivascular adipose tissue (PAT) contribute to VV neovascularization.

Methods:
We established a new mouse model of atherosclerosis, in which the carotid artery is partially ligated (CPL) and exogenous adipose tissue is transplanted in the perivascular area (PVAT). The three branches (external and internal carotid, occipital) of the left carotid artery (LCA) of 20- to 25- week-old male apolipoprotein E-deficient (ApoE-/-) mice were ligated. Then epididymal adipose tissue from a donor ApoE-/- mouse was transplanted around the LCA (CPL+PVAT, n=5). Carotid partial ligation alone was performed as a control (CPL, n=3). After 8 weeks, on western type diet, LCA was harvested with PAT after biotinylated-Lycopersicon Esculentum (Tomato) lectin perfusion staining. Next, epididymal fat tissue from a male enhanced green fluorescent protein (EGFP) mouse was transplanted around the LCA of another set of male ApoE -/- mice after CPL (n=4). After 8 weeks, LCA was harvested with PAT after perfusion staining of microvessels, embedded in plastic resin, and observed under a confocal microscope.

Results:
The transplanted adipose tissue engrafted and atherosclerotic lesion developed in LCAs. Intima/media ratio of CPL+PVAT group was similar with that of CPL alone group (p=0.39). Whereas, VV density in adventitial area (outside the elastic lamina within a distance of the thickness of neointima plus media, excluding PAT) near three -fold increased than CPL alone group (p<0.05). In the EGFP fat transplanted mice, a significant portion of VV was GFP positive (GFP positive /total microvessels in adventitia: 12.5 ± 6.2 % ).

Conclusions:
The vascular cells derived from PAT contribute to VV neovascularization, at least in part, in atherosclerosis.
Abstract 14993: Does Pregnancy Increase the Risk of Deterioration of Homograft Valves? A Systematic Review and Meta-analysis
Authors: Munoz-Mendoza Jerson , Pinto Miranda Veronica , Tamariz Leonardo , Garcia Mario
Published: April 2024

Introduction:
A previous meta-analysis found that pregnancy increases the risk of structural valve deterioration (SVD) of bioprosthetic valves. However both homografts and xenografts were included indistinctly in the analysis. The purpose of this study is to conduct a meta-analysis to determine if pregnancy independently increases the risk of SVD in women recipient of homograft and xenograft valves.

Methods:
We searched MEDLINE, EMBASE, CINAHL, Web of Knowledge, and Cochrane Library databases for articles published from inception until May 2015. Only cohort and case control studies were included. We calculated the relative risk (RR) and the corresponding 95% confidence interval (CI) of having SVD by pregnancy status using the DeSirmonian-Laird method. Meta-regression examined the RR of SVD by age, number of pregnancies and time from valve replacement to delivery.

Results:
Our search strategy yielded 23 publications; nine studies met inclusion criteria. Two studies (75 women) were performed in recipients of homografts. They were divided in two groups according to their history of pregnancies, 22 who were pregnant at least once and 53 who never were pregnant. Eight studies (1071 women) assessed SVD in women recipient of xenografts, including 282 women who had been pregnant and 789 who never were pregnant. Twenty (26.6%) and 341 (31.8%) women recipients of homografts and xenografts respectively developed SVD. Among the recipients of xenografts, the RR of having SVD in pregnant women was 1.70; 95% CI 1.26-2.29; p<0.01 (Figure), whereas it was 1.03 (95% CI 0.45-2.33; p<0.01) in recipients of homografts. None of the factors evaluated in meta-regression in recipients of xenografts were statistically significant.

Conclusion:
Pregnancy does increase the risk of SVD in recipients of xenografts, but no homografts. Homografts would be a better option than xenografts in women of childbearing age non suitable for long-term anticoagulation.
Abstract 14994: Androgen Receptor Modulates Androgen-mediated Enhancement of Ischemia-induced Neovascularization via Genomic Action
Authors: Lam Yuen Ting , Lecce Laura , Handelsman David J , Ng Martin K
Published: April 2024

Introduction:
Increasing evidence indicates that androgens regulate ischemia-induced neovascularization. However, the role of androgen receptor (AR), a ligand-dependent nuclear transcription factor, remains poorly understood with genomic and non-genomic mechanisms proposed.

Hypothesis:
Using AR knockout mice (ARKO), which contain a transcriptionally inactive AR due to an in-frame deletion of the second zinc finger of the DNA-binding domain of AR, we hypothesized that AR genomic function plays a role in modulating androgen-mediated augmentation of ischemia-induced neovascularization.

Methods and Results:
Wild type (ARWT) and ARKO were implanted with dihydrotestosterone (DHT) or placebo (P) pellets following induction of hindlimb ischemia (HLI). Laser Doppler Perfusion Imaging revealed that DHT enhanced blood flow recovery in ARWT post-HLI. By contrast, DHT-mediated enhancement of blood flow recovery was abrogated in ARKO. Ischemia-induced vasculogenesis was examined by flow cytometry to assess the levels of Sca1+/CXCR4+ progenitor cells. DHT augmented the levels of Sca1+/CXCR4+ progenitor cells in bone marrow (DHT: 10.87 ± 0.817 vs. P: 5.057 ±0.503, p<0.001) and circulating blood (DHT: 8.827 ± 1.122 vs. P: 5.150 ± 0.924) in ARWT at day 3 post-HLI. The augmentation of bone marrow and circulating Sca1+/CXCR4+ progenitor cell levels by DHT was absent in ARKO post-HLI. Transplantation of ARWT or ARKO bone marrow into irradiated recipients further revealed that ischemia-induced elevation of circulating progenitor cells was abolished in recipients with ARKO bone marrow. DHT augmented ischemia-induced HIF-1α expression (DHT: 2.39- vs. P: 1.4-fold increase at day 3 post HLI, p<0.05) and promoted the production of stromal derived factor-1 (SDF-1) in ARWT. However, DHT augmentation of HIF-1α and SDF-1 were attenuated in ARKO post-HLI. In vitro, DHT-induced HIF-1α transcriptional activity and DHT-augmented tubule formation of endothelial cells via paracrine effect were attenuated in cells isolated from ARKO.

Conclusions:
Augmentation of ischemia-induced bone marrow-derived progenitor cell mobilization and HIF-1α-associated angiogenesis by androgens is dependent on the genomic action of AR.