bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2211: Large Differences in Efficiency Among Fontan Patients Demonstrated In Patient Specific Models of Blood Flow Simulations
Authors: Marsden Alison L , Bernstein Adam J , Spilker Ryan L , Chan Frandics P , Taylor Charles A , Feinstein Jeffrey A
Published: July 2021

Background: Not all Fontan patients are “equal” despite similar hemodynamics using current diagnostic modalities. Recent advances in imaging and computational fluid dynamics simulations (CFDS) enable the evaluation of both previously unmeasurable parameters (e.g. efficiency (either at rest or with exercise)) and in patient-specific scenarios. We hypothesize CFDS at rest and simulated exercise will demonstrate large differences in pressure and efficiency among Fontan patients.

Methods: Using MRI-obtained anatomy and flow, time-dependent, 3-D simulations were performed using a custom finite element solver in 4 patient-specific Fontan models. Flow features, pressure, and energy efficiency were analyzed at rest and with increasing flow to simulate light, moderate and heavy exercise. Resistance boundary conditions enabled simulation at physiologic pressures and vasodilation with “exercise.”

Results: Large variations in geometry, efficiency (96 – 87% at rest, 90–75% with exercise) and mean SVC pressure were seen (figure

). Efficiency did not correlate with Fontan pressures and did not decrease linearly with increased exercise. The most efficient among these four particular patients was a traditional t-junction connection though it had one of the highest SVC pressures.

Conclusions: Geometries, efficiency and pressure levels vary dramatically among Fontan patients. Patients may have similar hemodynamic performance at rest, but large differences in both efficiency and pressure can be demonstrated during simulated exercise. CFDS and determination of patient specific efficiency may provide an additional tool for risk stratification among patients.
Abstract 2233: Biobehavioral Factors and Heart Failure Medication Adherence
Authors: Gary Rebecca A , Robinson Judith M , Clark Patricia C , McCarty Frances , Smith Andrew L , Dunbar Sandra B
Published: July 2021

Background:
Medication adherence in heart failure (HF) patients reduces hospitalizations and improves outcomes, yet it is variable. This study evaluated adherence rates and associated biobehavioral factors for two HF medications using objective (Medication Event Monitoring System; MEMS) and self-report approaches.

Methods:
The sample (n = 87) was primarily male (64.4%), Black (64.7%), NYHA class II (71%), married (56.9%) with left ventricular ejection fraction (LVEF) 26.6±14.2, age 55.5±10.4 years. Adherence for a HF medication and diuretic was monitored for 19.6 ±5.7 days using the MEMS. Relationships among clinical variables (NYHA class, LVEF, six-minute walk test [6MWT]; objective (MEMs) and self-reported (Morisky Medication Adherence Scale) medication adherence; medication self-efficacy (Perceived Self-Efficacy [SE] for Medication Compliance); medication taking self-regulation (Treatment Self-Regulation for Medication Taking); and HF knowledge (HF Knowledge Questionnaire) were analyzed using correlation coefficients and hierarchical multiple regression.

Results:
Adherence was 85.42% for the HF medication (n=74) and 83.42% (n=67) for daily diuretic. MEMS and Morisky scores were correlated for the HF medication (r=.389, p=.002) and diuretic (r=.392, p=.002). Medication SE was related to adherence for HF medication (r=.283, p=.025) and diuretic (r=.294, p=.028). Higher HF Knowledge Questionnaire scores were related to greater adherence for the HF medication (r=.316, p=.012) and diuretic (r=.359, p=.007). The model (marital status, HF knowledge, medication SE and 6MWT) yielded adj. R
2
=.26 (F =6.7, p<.001;) with medication SE (p<.001) and 6MWT (p=.053) as independent predictors of medication adherence. Clinical, demographic and medication self-regulation variables were not significant.

Conclusions:
Medication adherence in HF patients is related to modifiable factors of medication self-efficacy and HF knowledge. Improving medication self-efficacy, knowledge and showing patients tangible evidence of improvement in physical function such as increased 6MWT distance may lead to enhanced medication adherence.
Abstract 333: Vascular Endothelial Growth Factor-B (VEGF-B) Induces Myocardium-specific Angiogenesis via VEGFR-1 and Neuropilin-1
Authors: Markkanen Johanna E , Nurminen Markku T , Kivelä Antti , Heikura Tommi , Eriksson Ulf , Ylä-Herttuala Seppo
Published: July 2021

Growth factor gene therapy is a new, promising tool for treatment of myocardial ischemia. Development of safe and effective clinical applications requires optimal selection of growth factors and knowledge of the mechanisms involved. We have previously discovered that adenovirally over-expressed (Ad) VEGF-B
186
induces tissue-specific angiogenesis in the myocardium. Another VEGFR-1 specific ligand, placental growth factor (PlGF) induced angiogenesis both in the heart and skeletal muscle. We hypothesized that these two VEGFR-1 ligands utilize different angiogenic mechanisms. Unlike PlGF, the effect of VEGF-B was not dependent on the up-regulation of endogenous VEGF-A since soluble decoy VEGFR-2 did not block the effect. In contrast to PlGF or VEGF-A, the therapeutic effect of VEGF-B was not blocked by inhibition of nitric oxide synthesis by feeding the animals L-NAME, indicating that a novel angiogenic pathway was involved. Western blot (WB) analysis of the transduced tissues showed that in the myocardium AdVEGF-B
186
was proteolytically processed, while majority of the protein in the skeletal muscle was unprocessed. Processed form of VEGF-B binds to another angiogenic receptor neuropilin-1 (Nrp-1). Immunohistochemical staining and WB showed strong Nrp-1 expression in the myocardium while Nrp-1 expression was below detection limit in the skeletal muscle. In addition, down-stream molecules GIPC and GAIP were co-localized with Nrp-1 suggesting Nrp-1 receptor activation. Co-transduction with soluble decoy AdsNrp-1 or AdsVEGFR-1 blocked the angiogenic effects of VEGF-B
186
in the myocardium indicating that both receptors are involved in the angiogenic pathway. VEGF-B induces angiogenesis in the myocardium via VEGFR-1 and Nrp-1. This novel myocardium-specific angiogenic pathway offers a safe tool for growth factor therapies and provides new information about repair mechanisms of the heart.
Abstract 334: Cyclic GMP-dependent Protein Kinase Iα Dependent Regulator of G-protein Signaling 2 Activation Is Required for Early Cardiac Compensation to Pressure-overload
Authors: Takimoto Eiki , Ketner Elizabeth A , Koitabashi Norimichi , Zhang Manling , Nagayama Takahiro , Bedja Djahida , Gabrielson Kathleen L , Mendelsohn Michael E , Kass David A
Published: July 2021

In response to pressure-overload, the heart initially develops adaptive hypertrophy with enhanced contractility, but later decompensates with chamber dilation. Such maladaptation can be induced by activation of G
αq
-coupled signaling, whereas enhancing cyclic GMP-dependent protein kinase I-α (PKGI-α) by phosphodiesterase 5A inhibition (PDE5A-I) ameliorates pressure-overload pathobiology. A potential coupler of both pathways is RGS2 (regulator of G-protein signaling 2), which is activated by PKGI-α to suppress G
αq
-stimulation in vascular smooth muscle cells. Here we tested this signaling in hearts exposed to pressure-overload by transverse aortic constriction (TAC). RGS2 is up-regulated in the particulate fraction of control heart lysate within 48 hours of TAC. Unlike controls, RGS2
−/−
hearts display no early compensation to TAC, developing accelerated dilation and severe hypertrophy within 1week, with high mortality (Table

). Downstream signaling of G
αq
stimulation including ERK1/2, CaM kinase II and calcineurin is markedly activated or up-regulated in RGS2
−/−
-TAC versus RGS2
+/+
-TAC. In normal myocytes, RGS2 displays weak diffuse subcellular localization by confocal immunofluorescent histochemistry, whereas PKGI-α has a striated banding pattern. Stimulation of G
αq
(angiotensin II, 1μM; endothelin 1, 0.5μM) induces translocation of both RGS2 and PKGI-α to the sarcolemmal membrane, which is dependent on PKG activation. Similar translocation is observed in 48hours-TAC myocytes, but it declines by 1 week. Concomitant PDE5A-I (oral sildenafil; 200mg/kg/day) sustains PKGI-α and RGS2 at the membrane in RGS2
+/+
-TAC 1week, ameliorating hypertrophy, whereas PDE5A-I has no effect on RGS2
−/−
-TAC 1week (Table

). Thus RGS2 is an essential regulator of early compensation to pressure-overload, is regulated by PKGI-α activation, and also plays a key mechanistic role in the anti-hypertrophic effects from PDE5A inhibitors.

Results TAC 1 week (n = 4–6 for hemodynamics in each group)
Abstract 2250: Active Cascade Screening in Primary Inherited Arrhythmia Syndromes; Does it Lead to Prophylactic Treatment?
Authors: Hofman Nynke , Tan Hanno L , van Langen Irene M , Wilde Arthur A
Published: July 2021

Introduction
The congenital long QT syndrome (LQTS), Brugada syndrome (BrS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are primary inherited cardiac arrhythmia syndromes which may cause syncope and sudden cardiac death in young individuals. After establishing the disease-causing DNA mutation in probands, we actively conducted cascade screening to identify relatives who are also at risk of life-threatening arrhythmias. We studied how often this led to prophylactic treatment.

Methods and Results
We retrospectively collected data from our Cardiogenetics database and patient records. In 1996–2006, 118 probands with a disease causing mutation in one of the involved genes were identified and 446 relatives were tested positive for the disease causing mutation found in their family. These subjects subsequently underwent cardiologic investigation (ECG, exercise testing, Holter, ajmaline testing, echocardiography, where appropriate). We analyzed the numbers and percentages of identified carriers needing prophylactic treatment. Treatment was deemed necessary based on the results of cardiologic investigation, type of disease, previously reported properties (clinical and/or biophysical) of the mutation, familial occurrence of unexplained sudden death, and age of the subject. Treatment was initiated in 69% (197/285), 9% (5/54) and 71% (76/107) relatives in the LQTS, BrS, and CPVT families, respectively. Twenty-six carriers were lost to follow-up. Treatment included drug treatment (n=244) and implantation of pacemakers (n=26) or ICDs (n=8).

Conclusions
Cascade screening in families with LQTS, BrS or CPVT, which was based on DNA mutation carriership and subsequent cardiologic investigation, resulted in immediate prophylactic treatment in a substantial proportion of carriers (278/446, 62%), although it varies significantly between the different disease entities.
Abstract 2262: No Impact Of The Mitral Annuloplasty On Overall Survival In Patients With Ischemic Cardiomyopathy - Long-term Follow-up Study.
Authors: Golba Krzysztof S , Biernat Jolanta , Deja Marek A , Domaradzki Wojciech , Jasiński Marek , Dalecka Anna Maria , Malinowski Marcin , Roleder Tomasz , Twardowski Romuald , Wos Stanislaw
Published: July 2021

Good long-term results are reported after the mitral valve (MV) repair for ischemic regurgitation.

The aim of the study
was to identify predictors of the overall survival after routine MV repair in patients with ischemic cardiomyopathy.

Methods.
164 patients, 60.9±8.66 years old, with chronic ischemic mitral regurgitation and left ventricle ejection fraction (EF) = 30.7±6.04 undergoing coronary bypass with or without MV repair were prospectively followed for 5.1±1.63 years. A Cox proportional hazards model evaluated overall survival as a function of baseline age, sex, EF, mitral regurgitation jet area, left atrial area, atrial fibrillation, NYHA class, prior anterior or inferior myocardial infarction, medical comorbidities, MV repair, left ventricular plasty, left main and 3 vessel disease, venous graft to left anterior descending artery, number of grafts and year of operation. Treatment selection bias was controlled by deriving a propensity score for mitral annuloplasty.

Results.
Predictors included in the Cox regression model of overall survival are presented in table

. The ROC curve analysis revealed EF <30.0, (sensitivity and specificity - 61.7% and 59.0%, respectively) and serum creatinine >1.17, (45.6% and 77.2%) as a cut-off values in the prediction of overall survival.

Conclusions.
There is no impact of the mitral annuloplasty on overall survival in these patients. MV repair can be safely added to coronary bypass grafting in patients with ischemic cardiomyopathy.

Multivariable Cox regression analysis results
Abstract 2285: Acute and Chronic Improvement in Left Ventricular Diastolic Function Following Cardiac Resynchronization Therapy
Authors: Miske Glen , Tanabe Masaki , Thomas Nini C , Schwartzman David , Gorcsan John
Published: July 2021

Background:
Cardiac resynchronization therapy (CRT) has been shown to result in improvements in left ventricular (LV) systolic function, but its effects on diastolic function are not well understood. Our aim was to test the hypothesis that CRT acutely improves LV diastolic function and that these benefits are sustained in chronic follow-up.

Methods:
We studied 40 NYHA Class III–IV heart failure patients (65±10 yrs, ejection fraction 24±7%, QRS duration 166±26 ms, 62% ischemic) at baseline, 24 hours after CRT, and 6±3 mo. after CRT. A control group of 10 normal subjects were also studied. Quantitative pulsed wave and tissue Doppler measures of diastolic function included: mitral inflow peak E and A wave velocity, E deceleration time, mitral annular E′ velocity (septal and lateral sites) and estimation of LV filling pressure by E/E′.

Results:
All CRT patients had baseline diastolic dysfunction, as expected: Deceleration Time = 163±53 ms, E′ = 3.4±1.6 cm/sec, E/E′ = 40±20, peak E wave = 1.11±0.3 m/sec, peak A wave = 0.5±.3 m/sec, (all p < 0.05 vs. controls). Diastolic function acutely improved following CRT: Deceleration Time = 218±52 ms*, E′= 4.3±1.8 cm/sec*, and E/E′ = 29±19*, peak E wave = 1.01±0.26 m/sec*, peak A wave = 0.7±.34 m/sec* (all p < 0.05 vs. baseline). These beneficial effects of CRT were sustained 6±3 month following CRT (all p < 0.05 vs. baseline).

Conclusion:
CRT was associated with acute improvements in LV diastolic function. These improvements were sustained through chronic follow-up. These findings extend the understanding of beneficial effects of CRT on LV function.
Abstract 2286: Pseudonormalization Tendency of the Tei Index at High Filling Pressures -A Serious Limitation for its Use as a Myocardial Performance Index
Authors: Dandel Michael , Lehmkuhl Hans , Kemper Dagmar , Hetzer Roland
Published: July 2021

Background:
The potential advantage provided by the combination of systolic and diastolic parameters makes the Tei index (myocardial performance index) attractive. This index is prolonged during mild or moderate left ventricular (LV) systolic dysfunction. The influence of diastolic dysfunction is unclear. We assessed the reliability of the Tei index for the evaluation of LV dysfunction, in relation to the severity of systolic and/or diastolic impairment.

Methods:
To evaluate the systolic LV dysfunction associated with various degrees of diastolic dysfunction by the Tei index, the isovolumetric contraction and relaxation time (IVCT and IVRT) and the ejection time were measured by continuous wave Doppler in 155 consecutive patients accepted for heart transplantation (HTx) because of advanced dilated cardiomyopathy (DCM). To evaluate the diastolic dysfunction by the Tei index, the same Doppler measurements were performed in 200 HTx patients who showed isolated diastolic LV dysfunction with normal ejection fraction (LVEF ≥ 55%).

Results:
Although the Tei index was prolonged (0.67 ±0.16) in DCM patients, there was no correlation between LVEF and Tei index. The Tei index was even lower in NYHA IV in comparison to NYHA II–III patients (0.56 ±0.11 vs. 0.76 ±0.14; p <0.001)). The LVEF was 17.5 ±5% in NYHA IV and 27.2 ±6% in NYHA II–III patients (p <0.01). The IVRT was shorter (p<0.001) in NYHA IV (60.8 ±13 ms) than in NYHA II–III patients (113.9 ±19.5 ms). After HTx, due to initially prolonged IVRT, the Tei index was higher before than after the 1
st
post-HTx year (0.54 ±0.08 vs. 0.45 ±0.08; p<0.01). The Tei index was also lower (p<0.05) in patients with coronary allograft vasculopathy (CAV), than in those without (0.42 ±0.10 vs. 0.48 ±0.09). For both DCM and HTx patients there was a correlation between IVRT and Tei index (p <0.001; r = 0.71 and r =0.72, respectively) and also between LV enddiastolic pressure and Tei index (p <0.001; r = −0.69 and r = −0.74, respectively).

Conclusions:
The shortening of the IVRT due to the elevation of filling pressures in both severe systolic dysfunction (i.e. advanced DCM) and isolated diastolic dysfunction (post-HTx CAV) lowers the Tei index (pseudo-normalization tendency) and thus, in these clinical situations, the Tei index becomes misleading.
Abstract 137: Gab Family Scaffolding Adaptor Proteins are Essential for Postnatal Maintenance of Cardiac Function via Neuregulin-1/ErbB Signaling
Authors: Nakaoka Yoshikazu , Kamiya Atsunori , Minami Takashi , Sawa Hirofumi , Fujio Yasushi , Koyama Tatsuya , Hirota Hisao , Yamauchi-Takihara Keiko , Otsu Kinya , Hori Masatsugu , Hirano Toshio , Mochizuki Naoki
Published: July 2021

Backgrounds:
Grb2-associated binder (Gab) family proteins belong to scaffolding adaptor proteins and undergo tyrosine-phosphorylation after stimulation with various growth factors and cytokines. Tyrosine-phosphorylated Gab family proteins associate with tyrosine phosphatase SHP2 and p85 phosphatidylinositol-3 kinase subunit, leading to activation of extracellular signal-regulated kinase (ERK) and AKT, respectively. Among Gab family proteins, mRNAs of Gab1 and Gab2 were detected in the murine heart by RT-PCR. Since Gab1 and Gab2 are capable of complementing each other in some signaling pathways, we tried to elucidate the role of Gab family proteins in the myocardium by creating cardiomyocyte-specific Gab1/Gab2-double knockout (DKO) mice.

Methods & Results:
DKO mice were generated by crossing cardiomyocyte-specific Gab1-knockout mice with conventional Gab2-knockout mice. Although DKO mice were viable, they exhibited marked ventricular dilatation and deteriorated contractility with aging. Approximately 70% of DKO mice died of heart failure between 3 and 72 weeks. Among various growth factors, neuregulin-1β (NRG-1β), a paracrine factor shed from endocardial and microvascular endothelium in the heart, most strongly induced tyrosine-phosphorylation of both Gab1 and Gab2 and subsequent association of Gab1/Gab2 with SHP2 and p85. NRG-1β induced activation of ERK and AKT in the hearts of control mice, but not in those of DKO mice. Intriguingly, endocardial fibroelatsosis and abnormally dilated vessels were observed exclusively in the ventricles of DKO mice, suggesting the endothelial dysfunction in the heart. To explore the molecular target of NRG-1β/ErbB/Gab1/Gab2-signaling pathway in the myocardium, we performed DNA microarray analysis and found that administration of NRG-1β upregulated expression of an endothelium-stabilizing factor, angiopoeitin-1, in the myocardium of control mice, but not in those of DKO mice, which presumably accounted for the pathological abnormalities in the DKO mice hearts.

Conclusion:
In the NRG-1β/ErbB signaling, Gab1 and Gab2 of the myocardium are essential for both maintenance of myocardial function and stabilization of cardiac capillary/endocardial endothelium in the postnatal heart.
Abstract 141: Deletion of
Ptpn11
(Shp2) in Cardiomyocytes Leads to Dilated Cardiomyopathy
Authors: Kontaridis Maria I , Yang Wentien , Bence Kendra , Cullen Darragh , Wang Bo , Bodyak Natalya , Ke Qingen , Hinek Aleksander , Kang Peter , Liao Ronglih , Neel Benjamin G
Published: July 2021

Heart failure is the leading cause of death in the U.S. Delineating the pathways that regulate cardiomyocyte function is essential to understanding the pathogenesis of cardiac disease. Many cardiomyocyte signaling pathways activate protein tyrosine kinases, yet the role of protein tyrosine phosphatases (PTPs) in the heart is unknown. Here, we show that mice with cardiac-specific deletion of
Ptpn11
, the gene encoding the SH2 domain-containing PTP Shp2, rapidly develop a compensated dilated cardiomyopathy without an intervening hypertrophic phase. Primary Shp2 deficient cardiomyocytes are defective in Erk/MAPK activation in response to a variety of soluble agonists and pressure overload. Our results identify Shp2 as the first PTP known to have a critical role in cardiac function, suggest that Shp2’s cardio-protective role is mediated via control of the Erk/MAPK pathway, and have important implications for the pathogenesis of cardiac defects in the human genetic diseases Noonan Syndrome and LEOPARD Syndrome, which are caused by
PTPN11
mutations.
Abstract 2305: Pulmonary Vascular Reactivity And Prognosis In Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Skoro-Sajer Nika , Hack Nicklas , Sadushi Roela , Jakowitsch Johannes , Bonderman Diana , Kneussl Meinhard , Klepetko Walter , Lang Irene
Published: July 2021

Hemodynamic responder status defined as an acute decrease of mean pulmonary arterial pressure (mPAP)>10mmHg and below 40mmHg is associated with improved outcome in patients (pts) with pulmonary arterial hypertension (PAH). Pulmonary vascular reactivity to nitric oxide (NO) is controversial in chronic thromboembolic pulmonary hypertension (CTEPH). We speculated that the magnitude of the acute decrease in mean pulmonary artery pressure (mPAP) after exposure to NO might reflect the degree of small vessel disease in CTEPH and thus, affect long-term outcome.

Methods: Right heart catheterization was performed in 62 (55 Â ± 15 years, 32 female) pts with major-vessel CTEPH, at baseline and during inhalation of 40ppm NO. Within 25Â±15 days patients underwent pulmonary endarterectomy (PEA). Pts were followed for 11.3Â±26 months. Predictors of survival were analyzed by Cox regression analysis, and survival was described by Kaplan-Meier curves.

Results: Significant reductions in mean pulmonary arterial pressure (mPAP; p<0.001), pulmonary vascular resistance (PVR; p<0.001) and an increase in mixed venous oxygen saturation following NO inhalation were demonstrated (p<0.001) by a paired t-test. Stepwise multivariate analysis revealed the relative change of PVR after NO inhalation as a predictor of survival. Patients whose PVR during NO inhalation declined below 789.8 dynes.s.cm-5 had significantly better outcome than patients with above median PVR. There was a strong negative correlation between the relative change of PVR under NO and recurrent pulmonary hypertension after PEA (p=0.02).

Conclusions: Patients with operable CTEPH demonstrated acute pulmonary vascular reactivity, mostly not corresponding to a complete responder status, but accounting for a wide range of decreases of mPAP [change of mPAP (%) (−10.9Â±14)] and PVR [change of PVR (%) (−17 Â±15)]. Reduction of PVR under 800 dynes.s.cm-5 after inhalation of NO was associated with better outcome. Responsiveness to inhaled nitric oxide is a predictor for mid-term survival in adult patients with CTEPH undergoing PEA.
Abstract 2307: Seattle Heart Failure Model Overestimates Time to Mortality in Patients Referred for Heart Transplantation
Authors: Giamouzis Grigorios , Georgiopoulou Vasiliki , Kalogeropoulos Andreas , Smith Andrew , Butler Javed
Published: July 2021

Background
: Accurate determination of time to death in advanced heart failure (HF) patients is critical for appropriate transplant candidate selection. Recently, Seattle Heart Failure Model (SHFM) was introduced to assess HF prognosis, however it was developed from a general HF population and its accuracy in advanced HF patients has not been reported.

Methods
: We collected data on 51 advanced HF patients referred for transplant evaluation who died during follow-up (mean age 57.4±17.5 years, 70.1% male, and 56.9% white). Time to death prediction by the SHFM was assessed by plotting actuarial survival time vs. model error (=predicted-actual). Gender and race based stratified analysis were also performed.

Results
: Median ejection fraction was 0.15 (25%–75%: 0.10 – 0.25), heart rate was 87±19 bpm, and systolic blood pressure was 117±22 mmHg. Overall 90.2% patients were on ACE inhibitor or angiotensin receptor blockers, 82.4% on beta-blockers, and 74.6% had a defibrillator implanted. Median expected survival by the SHFM was 6.4 (3.8 –9.7) years. Median actual survival was 2.0 (1.1–3.9) years. Residual analysis showed that the SHFM overestimated survival by 3.8 (1.5– 6.5) years, p<0.001, Fig 1

. Overall 86.3% patients lived shorter than projected survival. The SHFM overestimated survival more in black vs. white patients (4.5 years, 25%–75%: 2.3–7.9 years in blacks vs. 2.8 years, 25%–75%: 0.7– 6.0 years in whites, p=0.07). No significant gender differences were noted.

Conclusion
: The SHFM significantly overestimates survival in advanced HF patients referred for transplantation, especially in blacks. Further studies are needed to modify and validate the SHFM in these patients.
Abstract 2311: Clinical Predictors Of Survival In Heart Failure Patients Following Cardiac Resynchronization Therapy
Authors: Couri Daniel M , Lin Grace , Webster Tracy L , Brady Peter A
Published: July 2021

Introduction:
Appropriate selection of patients (pts) with heart failure (HF) who may benefit from cardiac resynchronization therapy (CRT) is difficult. We sought to identify a clinical risk score to better risk stratify patients prior to CRT implantation.

Methods:
Pts undergoing CRT at Mayo Clinic from 2000 –2005 were included. Multiple clinical variables (age, gender, anemia (Hgb <10g/dL), RF (creatinine clearance ≤ 60ml/min/1.73m
2
), hyponatremia (Na ≤130mEq/L), elevated BNP level (>500pg/ml), etiology, EF ≤20%, and advanced HF (NYHA functional class III–IV) were assessed with outcomes following CRT. Multivariate analysis was used to determine a clinical risk score.

Results:
A total of 496 patients (80% males) age 68 ± 12 years (62% ischemic cardiomyopathy, EF 22% ± 8%) were included. In univariate analysis relative risk (RR) was > 1 for RF (RR 1.8, CI 1.3–2.8; p = 0.002), anemia (RR 3.3, CI 1.8 –5.5; p = 0.001), hyponatremia (RR 3.4, CI 1.4 – 6.9; p = 0.008), elevated BNP (RR 2.9, CI 1.6 –5.7; p < 0.001), ischemic cardiomyopathy (ICM) (RR 1.8, CI 1.2–2.7; p < 0.002), EF ≤ 20% (RR 1.5, CI 1.0 –2.1; p = 0.033), and advanced HF (RR 2.5, CI 1.5– 4.9; p < 0.001). Following multivariate analysis RF, anemia, ICM, and advanced HF remained significant predictors of poor outcome (p >0.01 for all). Survival with 3 or more of these clinical risk factors was significantly worse than with less risk factors (p <0.01, Figure

).

Conclusions:
Pre-implant clinical risk factors including anemia, RF, ICM and advanced HF predict worse outcome following CRT with ≥3 variables predicting >2-fold increased risk of death or heart transplantation. These factors should be considered when selecting pts prior to CRT.
Abstract 2314: Altered Metabolism of Asymetric Dimethylarginine (ADMA) is Associated with Endothelial Dysfunction and Negative Arterial Remodelling After Heart Transplantation
Authors: Wilson Andrew , Virani Sean , Holweg Cecile , Kielstein Jan , Bode-Boger Stefanie , Valantine Hannah , Cooke John P , Fearon William F
Published: July 2021

Cardiac allograft vasculopathy (TAV) is a diffuse and progressive form of coronary artery disease occurring after heart transplantation (HT) characterized by endothelial dysfunction (ED) and negative arterial remodeling. However, TAV risk factors are not well understood. We hypothesized that asymmetric dimethylarginine (ADMA), a circulating inhibitor of nitric oxide synthase, mediates HT related ED and remodeling.

Methods and Results
Forty eight consecutive cardiac transplant recipients underwent baseline angiography within 8 weeks of cardiac transplantation and at 1 year after transplantation. Intravascular ultrasound indices were measured at baseline and 1 year in all and coronary response to infused acetylcholine and glyceryl trinitrate at 1 year as a measure of ED in 31 subjects. ADMA and its circulating metabolite symmetric DMA (SDMA) were measured at 8 weeks and 1 year by LC-mass spectroscopy. Rejection was diagnosed histologically in endomyocardial biopsies and subjects were subdivided into those with without treated rejection in the first year after HT. Responses to Ach were significantly impaired in patients with a history of treated rejection in the first year after transplant versus those without rejection (mean % change vessel diameter ± SD; −19.4 ± 12.7 versus −8.4 ± 10.2, p = 0.026). There was no difference in response to glyceryl trinitrate in those with and without rejection. Plasma ADMA levels decreased significantly after HT (0.55 ±0.12 versus 0.48 ± 0.09 micromol/l, p <0.001). Using stepwise multivariate regression in a model including age, gender, lipid levels, glucose and blood pressure, plasma ADMA was an independent correlate of Ach coronary artery response 1 year after transplant (p = 0.004, R2 = 46%). Other predictors were female gender and rejection. The ADMA/SDMA ratio (a marker of ADMA breakdown) was correlated inversely with change in vessel volume and change in lumen volume as measured by IVUS between baseline and 1 year (r = −0.036, p = 0.04).

Conclusion
Levels of ADMA correlated with impaired endothelial function as did episodes of treated rejection. The ADMA/SDMA ratio, a marker of ADMA breakdown, correlated with negative arterial remodeling. Abnormalities in ADMA metabolism may contribute to the pathogenesis of CAV.
Abstract 2334: Head-to-head Comparison of Whole-Heart Coronary MR and 40/64 slice Multidetector-CT Angiography for Detection of Coronary Artery Stenosis.
Authors: Pouleur Anne-Catherine , le Polain de Waroux Jean-Benoit , Kefer Joelle , Goffinet Céline , Vanoverschelde Jean-Louis , Gerber Bernhard L
Published: July 2021

Purpose
. Whole-heart magnetic resonance coronary angiography (WH-MRCA) has been recently proposed for non-invasive coronary imaging. Early studies have suggested that WH-MRCA might have similarly high diagnostic accuracy for detection of coronary disease as multidetector CT (MDCT). Yet, no direct comparison between both techniques has been performed. The aim of the present study was therefore to perform a head-to-head comparison of both techniques for detection of significant coronary stenoses using invasive cardiac catheterization as reference standard.

Methods.
Seventy-seven consecutive patients (56 M, 61±14 years) prospectively underwent free-breathing 3-dimensional WH-MRCA and 40/64-slice MDCT before cardiac catheterization. WH-MRCA and MDCT images were visually graded by 2 blinded observers and the diagnostic accuracy of both methods for detecting >50% luminal diameter stenoses (DS) in segments and vessels >1.5 mm size was compared using quantitative angiography (QCA) as reference method.

Results.
MDCT was successfully completed in all 77 patients in < 5 minutes. By contrast, WH-MRCA failed in 9 patients (12%) because of poor navigator performance and lasted 20±4 minutes (p<.01 vs MDCT). According to QCA, out of 992 segments > 1.5 mm diameter, 49 presented >50% DS. If all segments including non interpretable segments were considered, WH-MRCA had lower sensibility (35/49 or 71% vs. 45/49 or 92%, p<0.001), lower specificity (644/943 or 68% vs. 863/943 or 92%, p<0.001) and accuracy (679/992 or 68% vs. 908/992 or 92%, p<0.001) for detection of coronary stenosis than MDCT. However if only interpretable segments were considered, the sensitivity (35/37 or 95% vs. 45/46 or 98%, p=0.58), specificity (644/689 or 93% vs. 863/917 or 94%, p=0.67) and diagnostic accuracy (679/726 or 94%, vs. 908/963 or 94%, p=0.58) of WH-MRCA and MDCT for detection of >50% DS was similar. This was also the case on per-vessel basis.

Conclusion.
In the present study, MDCT had higher success rate than WH-MRCA. Therefore on an intention to diagnose basis, MDCT was superior to WH-MRCA. However, the diagnostic accuracy of WH-MRCA on per-segment and per-vessel basis was not statistically different from MDCT if only interpretable segments were considered.
Abstract 2341: Myocardial Ultrasound Tissue Characterisation in Children after Kawasaki disease
Authors: Leonardi Benedetta , Giglio Vincenzo , Pasceri Vincenzo , de Zorzi Andrea , Sanders Stephen P
Published: July 2021

Background: Reports of late follow-up of patients with Kawasaki Disease (KD), even with no epicardial coronary artery disease, have demonstrated abnormal vascular reactivity and myocardial perfusion. Left ventricular (LV) function is usually normal in KD patients during long-term follow-up. However, data regarding the myocardial properties of these children are lacking. Ultrasound tissue characterization (UTC), under some circumstances, appears to be predictive of subsequent development of myocardial dysfunction.

Methods and Results: We performed UTC analysis in 22 asymptomatic KD patients, mean age 6.6±3.4 years, 17 males, with a mean follow-up of 4.8±3.4 years after the illness. Coronary aneurysms were present in 8 patients (mean age 7.8±5.3 years). Cyclic variation of integrated backscatter (cvIBS) and calibrated integrated backscatter (cIBS) were assessed in 16 LV myocardial segments. Tissue Doppler imaging (TDI) at the mitral annulus was performed to assess LV diastolic function. All UTC and TDI data were compared to 22 age-matched controls, mean age 6.6±3.4 years. All patients had normal LV systolic function and wall motion score index (WMSI) compared to controls (EF 60.3±4.0% vs 60.8±4.4%, p=0.64, WMSI 1 vs 1, p=NS respectively). Myocardial velocities in systole and diastole by TDI did not differ significantly between patients and controls. CvIBS and cIBS mean values showed significant differences, for all segments sampled, between patients and controls (7.8±0.8 dB vs 8.9±0.6 dB, p<0.001, and 28.6±3.2 dB vs 25.2±1.0 dB p< 0.001 respectively). Neither cvIBS nor cIBS differed significantly between patients with and without aneurysms (7.9±0.8 dB vs 7.8±0.8 dB, p=0.84, and 30.3±4.3 dB vs 27.7±2.3 dB, p=0.20 respectively).

Conclusions: We detected widespread differences in myocardial physical properties between KD patients and controls late after the acute disease, despite normal LV function and independent of demonstrable coronary abnormalities. These differences could be related to cellular damage induced by occult myocardial ischemia or could represent abnormalities of small myocardial vessels. Further studies are needed to confirm these findings in a larger group of patients and to determine the clinical significance.
Abstract 2345: Improving Outcomes in High Risk Tetralogy of Fallot Patients with Right Ventricular Outflow Tract Stenting
Authors: Dohlen Gaute , Chaturvedi Rajiv , Benson Lee N , Fruitman Deborah , Osawa Akira , Lee Kyong-Jin
Published: July 2021

Background:
Symptomatic infants with tetralogy of Fallot (TOF) and hypoplastic pulmonary arteries have higher risk for primary surgical repair. In our institution, palliation with only balloon angioplasty of the right ventricular outflow tract (RVOT) and pulmonary valve has been inconsistent and short-lived.

Objectives:
To evaluate our experience with percutaneous transcatheter stent implantation in the RVOT in symptomatic TOF patients.

Methods:
Retrospective review at the Hospital for Sick Children in Toronto, Canada from 1994 until 2007 (Group I). Outcomes were compared with our institutional primary surgical repair patients (n = 44, Group II).

Results:
Ten stent procedures performed in 8 patients. Median age at first intervention was 22 days (range, 3 to 119). Median weight was 3.2 kg (2.1 to 4.1). Indication for intervention was desaturation below 70% or prostaglandin dependency. Two patients required a second stenting procedure for progressive RVOT obstruction at 67 and 122 days of life. There were no major procedural complications. Discharge post stent implantation occurred at a median of 4 days (1 to 12). Median number of days from initial stent implantation to next intervention was 108 days (44 to 315). Left and right pulmonary artery diameter Z-score increased from a median of −4.3 and −3.5 to −0.9 and −0.8 respectively before surgery. For Group I and II respectively, surgical data were: repair at median age of 142 days (44 to 413) compared to 24 days (5 to 112) (P<0.001), median weight at surgery 5.3 kg (4.0 to 9.3) and 3.2 kg (2.0 to 5.9) (P<0.001), median bypass time 99 minutes (66 to 127) and 118 minutes (54 to 264) (P=0.03), median ventilator days 4 (0 to 11) and 6 (1 to 97) (P=0.08), median days in intensive care unit was 5 (2 to 12) versus 8 (2 to 161) (P=0.09), time to discharge was 16 days (5 to 29) and 16 days (6 to 230) (P=0.35). There was no mortality in Group I and 2 late hospital deaths in Group II.

Conclusion:
Stenting of the RVOT in TOF patients safely and effectively palliated symptomatic patients. This promoted development of more favourable pre-operative conditions and translated to excellent surgical outcomes. This approach represents a powerful adjunct to the management armamentarium for this challenging patient population.
Abstract 2347: Pulmonary Regurgitation: The Impact on Right Ventricle and the Effect of Percutaneous Pulmonary Valve Replacement
Authors: Søndergaard Lars , Vejlstrup Niels G , Theilade Simone , Nilsson Jens C , Boudjemline Younes , Bonhoeffer Philipp
Published: July 2021

Background
Despite successful repair of tetralogy of Fallot (TOF), the life expectancy for these patients remains lower than in the general population. This is mainly due to free pulmonary regurgitation (PR). The importance of maintaining a competent valve has been emphasized, but the optimal timing for intervention remains to be established. The purposes of this study were in a pig model to investigate the consequences of the duration of free PR on RV, and the reversibility of these changes after percutaneous pulmonary valve replacement.

Methods
Thirtysix farm pigs were divided into four groups (A, B, C and D) of nine pigs. At baseline group A, B and C had a percutaneous stent inserted into the pulmonary annulus to create free PR. After 4, 8 and 12 weeks, respectively, group A, B and C underwent percutaneous valve replacement. In order to allow remodelling of RV, the pigs were observed for four weeks after valve insertion before euthanasia. To examine RV function, MRI was performed before stent insertion, before valve replacement, and before euthanasia. Group D served as controls and underwent five MRI examinations: at baseline as well as after four, eight, twelve and sixteen weeks.

Results
When comparing the group D with group A, B & C, RVEDV and RVESV were found to gradually increase over time. Furthermore, these volumes normalised after valve replacement in group A and B, but remains increased in the group C. Similar, RVEF was normal after valve replacement in group A and B, but impaired in the group the long-term free PR compared to the controls.

Conclusion
Better timing of valve replacement in patients with free PR after TOF repair is of outermost clinical relevance. This study examined the impact of free PR on RV in a pig model. Despite the relative short duration of the volume overload, the RV underwent irreversible changes. This may be explained by the fact that, in contrast to TOF, the RV is not hypertrophic. The study showed that RV tolerates volume overload from free PR for a certain time, but too late intervention will cause irreversible deterioration of the ventricular function. Thus, the model may serve to identify predictors, e.g. tissue-Doppler measurements or natriuretic peptides, for RV function after valve replacement and thereby optimise timing of intervention.
Abstract 2353: Angiopoietin Expression in Children Following Cardiopulmonary Bypass
Authors: Giuliano John S , Lahni Patrick M , Bigham Michael T , Nelson David P , Manning Peter B , Bogenshutz Lois , VanVliet Tracey , Wong Hector R , Wheeler Derek S
Published: July 2021

Introduction:
Capillary leak syndrome (CLS) is a serious, potentially life-threatening problem in children with congenital heart disease (CHD) that is partly related to the host inflammatory response following cardiopulmonary bypass (CPB). The angiopoietins are a family of vascular growth factors that are necessary for angiogenesis. Two members of the angiopoietin family are well characterized in humans - angiopoietin-1 (angpt-1) and angpt-2 - both of which appear to act on the Tie2 receptor, found primarily on vascular endothelial cells. Angpt-1 protects against capillary leak, while angpt-2 promotes increased vascular permeability and potentiates inflammation.

Hypothesis:
We hypothesized that plasma angpt-2 levels increase following CPB and correlate with indices of systemic inflammation and capillary leak.

Methods:
Plasma samples were obtained at baseline and at 0, 4, and 24 h after CPB in 49 children (median age 5 mo) with CHD. Troponin-I, angpt-1, angpt-2, VEGF, and soluble Tie2 (sTie2) were measured via a commercially available ELISA. Cytokines were measured using a multiplex cytokine assay.

Results:
CPB (mean CPB 119 min, cross-clamp, 71 mins) increased troponin-I, IL-6, IL-8, and IL-10 expression. Plasma angpt-2 levels increased by 6 h (952 pg/mL vs 462 pg/mL, p<0.05) and remained significantly elevated at 24 h after CPB (1850 pg/mL, p<0.05). Plasma angpt-1 levels remained unchanged immediately after CPB, but were significantly decreased at 24 h after CPB (635 pg/mL vs 991 pg/mL, p<0.05). Similarly, plasma sTie2 levels increased after CPB (6.4 ng/mL vs 2.86 ng/mL, p<0.05) before returning to baseline by 6 h after CPB. Plasma VEGF levels were not different at any timepoint. Plasma angpt-2 levels after CPB signficantly correlated with troponin-I, IL-6, IL-8, and IL-10 levels. There was a significant correlation between plasma angpt-2 levels and CPB time. Finally, higher plasma angpt-2 levels at 6 h correlated significantly with increased length of stay in the CICU (r=0.86; p<0.0001).

Conclusions:
Angpt-2 appears to be an important biomarker of vascular endothelial injury and capillary leak following CPB in children with CHD. Further studies on the role of angpt-2 in the pathophysiology of CLS following CPB are warranted.
Abstract 2355: A Randomized Comparison of Triple Antiplatelet Therapy with Dual Antiplatelet Therapy after Drug-Eluting Stent Implantation:
D
rug-
E
luting Stenting Followed by
C
ilostazol treatment reduces
LA
te
RE
stenosis in Patients with
DIABETES
mellitus: DECLARE - DIABETES Trial
Authors: Park Seong-Wook , Lee Seung-Whan , Kim Young-Hak , Yun Sung-Cheol , Park Duk-Woo , Lee Cheol Whan , Hong Myeong-Ki , Kim Hyun-Sook , Ko Jae-Ki , Park Jae-Hyeong , Lee Jae-Hwan , Choi Si Wan , Seong In-Whan , Cho Yoon Haeng , Lee Nae-Hee , Kim June Hong , Chun Kook-Jin , Park Seung-Jung
Published: July 2021

Objectives:
To determine whether cilostazol improves the efficacy of drug-eluting stent (DES) in patients with diabetes mellitus (DM).

Background:
Cilostazol has been reported to reduce neointimal hyperplasia and restenosis after bare-metal stent (BMS) implantation. But it is not known that its effect is extrapolated to drug eluting stent (DES) in patients with DM.

Methods:
This randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin, clopidogrel and cilostazol, triple group, n=200) and dual antiplatelet therapy (aspirin and clopidogrel, standard group, n=200) for 6 months in patients with DM receiving DES. The primary end point was in-stent late loss at 6-month angiography according to the intention-to-treat principle.

Results:
The both groups had similar baseline clinical and angiographic characteristics. The in-stent (0.25±0.53 mm vs. 0.38±0.54 mm, p=0.025) and in-segment (0.42±0.48 mm vs. 0.53±0.49 mm, p=0.031) late loss were significantly lower in the triple versus standard group. Six-month in-segment restenosis (8.0% vs. 15.6%, p=0.033) and 9-month target lesion revascularization (TLR) (2.5% vs. 7.0%, p=0.034) was significantly lower in triple group versus standard group. At 9 months, major adverse cardiac events (MACE) including death, myocardial infarction, and TLR had a lower tendency in triple group versus standard group (3.0% vs. 7.0%, p=0.066). Subgroup analysis showed that triple plus SES patients had significantly lower in-segment restenosis (0%, 0/88) than standard plus SES (8%, 7/88, p=0.014), triple plus PES (17.3% 13/75, p<0.001), and standard plus PES (24.1%, 19/79, p<0.001) patients. On the multivariate analysis, SES and the use cilostazol were strong predictors of restenosis and TLR.

Conclusions:
In patients with DM, compared with dual antiplatelet therapy, triple antiplatelet therapy after DES implantation is associated with a decrease in angiographic restenosis as well as the extent of late luminal loss, resulting in reduced risk of 9-monthTLR.
Abstract 2359: Clinical Relevance Of Clopidogrel-hyporesponse To Subacute Stent Thrombosis
Authors: Wetzel Thomas , Schulz Martin , Schulze-Waltrup Norbert , Dedner Ralf , Weber-Albers Joachim , Schmitz Dietmar , Marks Maritta , Heuer Hubertus
Published: July 2021

Background:
It could be shown in various investigations that a reduced response to clopidogrel (Clo) after PCI and stent placement is associated with a significantly worse cardiovascular outcome. At the moment no generally accepted normal values for clopidogrel-response exist.

Methods:
The clopidogrel-response was investigated in 2847 patients (mean age 63,5 +/− 10 years, 67% male, 33% female) undergoing PCI with stent placement in a prospective clinical study over 34 months (elective PCI by chronic stable angina: n=1907 (67%) and acute PCI by acute coronary syndrome (STEMI, NSTEMI): n=940 (33%). The platelet aggregation was analysed conventionelly using an aggregometer 6 –24 hours after application of 600 mg clopidogrel (loading dose) by adding 20 μmol/L adenosine diphosphate (ADP) to citrate plasma (Aggregometer PAP 4 MOELAB, Hilden, Germany).

Results:
In a follow-up period of 30 days after the intervention a subacute stent thrombosis occured in n=51 pts (1,8%). In n=46 (90%) of these patients the ADP-induced platelet final aggregation after Clo (post-treated) was >30% compared with the baseline of each patient without Clo (pre-treated). This corresponds to a platelet inhibition <70%. Taking this value as “cutoff value” results in a responder rate of 68,7% (n=1958) and a hyporesponder rate of 31,2% (n=889) of the entirety of patients. 5,2% (n=46) of the hyporesponders developed a subacute stent thrombosis.

Conclusions:
Clopidogrel (Clo) hyporesponders have a significantly increased risk of developing a subacute stent thrombosis after coronary stent placement. 90% of these endangered patients are identified with a cutoff value of platelet inhibition <70% respectively final aggregation > 30% showing the importance of periinterventional evaluation of the Clo-response status of each patient. If these patients would profit from an intensified antiplatelet strategy (for example increased doses of Clo) should be investigated in further studies.