bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2406: Coronary Microvascular Function as a Target for Prevention of Systolic Heart Failure in Chronic Valvular Heart Disease: Aortic Regurgitation versus Mitral Regurgitation
Authors: Okui Hideki , Hamasaki Shuichi , Ishida Sanemasa , Ogawa Masakazu , Saihara Keishi , Orihara Koji , Shinsato Takuro , Kubozono Takuro , Kuwahata So , Ninomiya Yuichi , Fujita Shouji , Takumi Takuro , Yoshikawa Akiko , Iriki Yasuhisa , Tei Chuwa
Published: July 2021

Background:
The coronary microvascular vasodilating function is an important determinant of patient outcomes in a number of clinical settings, including coronary artery disease, hypertensive heart disease, or cardiomyopathy. However, the characteristics or the implication of coronary microcirculation in valvular heart disease has not been fully elucidated. The present study was designed to assess coronary vasodilating function and its effects on systolic function in patients with aortic regurgitation (AR) and mitral regurgitation (MR).

Methods:
Forty-four consecutive patients (66 yrs) with moderate to severe AR and 45 consecutive patients with moderate to severe MR (64 yrs) were enrolled for this study. All patients were free of coronary artery stenosis. Fifty-one age-matched patients without underlying cardiovascular disease served as controls. Endothelium-dependent and endothelium-independent vasodilating function of resistance coronary artery were assessed by coronary blood flow (CBF) response to acetylcholine and papaverine, respectively. Left ventricular ejection fraction (LVEF) was determined by echocardiography as an indicator of systolic function.

Results:
In patients with AR, both %change in CBF response to acetylcholine and papaverine were significantly lower than controls (32 ± 61 vs 64 ± 84, 172 ± 87 vs 268 ± 105, p < 0.05, p < 0.01, respectively). Further, %change in CBF response to acetylcholine positively correlated with LVEF (r = 0.45, p < 0.01). In patients with MR, %change in CBF response to papaverine was significantly lower than controls (221 ± 123 vs 268 ± 105, p < 0.05), but %change in CBF response to acetylcholine was comparable with controls. Moreover, neither %change in CBF response to acetylcholine nor CBF response to papaverine had significant correlation with LVEF.

Conclusion:
In patients with AR, both endothelium-dependent and endothelium-independent vasodilating function of resistance coronary artery were deteriorated. Further, endothelium-dependent vasodilating function may be associated with left ventricular systolic function. Our findings indicate coronary microvascular endothelial dysfunction as a potential target for prevention of systolic heart failure in patients with AR.
Abstract 2416: Progressive Improvement in Cardiac Performance produced by Continuous Aortic Flow Augmentation in Patients Hospitalized with Acute Decompensated Heart Failure: Results from the MOMENTUM Trial
Authors: Zile Michael R , Colombo Paolo , Mehra Mandeep , Greenberg Barry , Brown Scott , Konstam Marvin
Published: July 2021

Previous studies indicate that superimposing continuous aortic flow augmentation (CAFA) on pulsatile aortic flow yields vasodilation, unloading, and improved cardiac performance. Whether improvement in indices of cardiac performance are dependent or independent of changes in hemodynamic load has not been examined. Multi-center Trial of Orqis® Medical Cancion® System for Enhanced Treatment of heart failure (HF) Unresponsive to Medical Therapy (MOMENTUM) is a randomized trial comparing CAFA plus medical therapy (n = 109) vs. medical therapy alone (n = 59) in patients hospitalized with HF inadequately responsive to therapy. Entry required reduced LVEF and cardiac index, elevated pulmonary capillary wedge pressure (PCWP), and either impaired renal function or high diuretic requirement, despite IV inotrope or vasodilator treatment. CAFA was achieved for up to 96 hrs using an arterial-to-arterial circuit (flow up to 1.5 L/min). Changes in cardiac performance were assessed using the relationship between stroke work (stroke volume x [Mean blood pressure-PCWP] x 0.00133, kg*cm) and PCWP. Figure shows hemodynamic effects (mean ± SEM) at baseline (B) and at hours post-B time. CAFA progressively improves LV performance (↑ Stroke Work and ↓ PCWP, p < 0.05 for both) resulting in an upward-leftward shift in the Starling function curve. In contrast, medical therapy alone resulted in no change in cardiac performance (↓ Stroke Work and ↓ PCWP, p < 0.05 for both), no shift in Starling curve. CAFA treatment, independent of changes in both preload and afterload, increased stroke work and decreased PCWP by progressively improving cardiac performance.
Abstract 2422: Short Term Effects of Milrinone on Biomarkers in Severe Heart Failure
Authors: Lanfear David , Gupta Ramesh C , Bazari Rasha N , Hasan Reema , Williams Celeste , Czerska Barbara , Tita Cristina , Sabbah Hani N
Published: July 2021

Introduction:
Inotrope use is associated with adverse outcomes in heart failure (HF), raising concern that it may cause or accelerate myocardial injury/damage. Whether biomarkers of myocardial necrosis, stretch, inflammation and apoptosis change in response to inotrope initiation is not known.

Methods:
Ten patients with severe HF and cardiac index < 2.0 L/m/M2 who were planned to receive intravenous milrinone were studied. All patients were at bed rest in cardiac intensive care unit. Blood was drawn immediately before initiation of milrinone and after 24 hours of continuous infusion. Milrinone dosing was at the discretion of the patient’s attending physician (0.375 –0.5 mcg/kg/min were used). Blood samples were immediately centrifuged, plasma aliquoted, and frozen at -70°C. Troponin I (TnI), Myoglobin, N-terminal pro-BNP (NTproBNP), interleukin 6 (IL6), Tumor Necrosis Factor α (TNF α), soluble Fas (sFas), and Fas ligand (FasL) levels were measured. TnI levels were replicated to assess precision of measurement, yielding a correlation coefficient > 0.995 and power > 90% to detect a mean difference as small as 0.02 ng/ml. Statistical comparisons were made between baseline levels and 24 hour levels using the paired t-test. P values < 0.05 were considered significant.

Results:
Baseline mean biomarker levels, 24 hour levels, absolute change, percent change, and associated p-values are shown in the Table

. Troponin I was elevated at baseline in all patients (range 0.0205– 0.56 ng/ml). There was no significant change in TnI after 24 hours of milrinone compared to baseline. There were significant improvements in NTproBNP, IL6, TNF α, sFas, and FasL.

Conclusions:
In this sample of patients with severe HF and reduced cardiac output, all had elevated troponin at baseline, consistent with ongoing myocardial damage. Initiation of milrinone therapy did not result in changes indicative of accelerated myocardial injury, and was associated with salutary effects on other markers.

This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).

Change in Biomarker Levels at 24 hours of Milrinone Therapy
Abstract 2423: B-type Natriuretic Peptide Upregulates Erythropoietin Receptor Gene Expression via Protein Kinase G in Heart Failure
Authors: Ohyama Yoshiaki , Tanaka Toru , Shimizu Takehisa , Doi Hiroshi , Koitabashi Norimichi , Iso Tatsuya , Nakano Akihiko , Arai Masashi , Kurabayashi Masahiko
Published: July 2021

Backgroud:
Recent studies demonstrated non-hematopoietical effects of Erythropoietin (Epo) and its receptor (EpoR) in a variety of tissues including cardiovascular system. Epo treatment improves cardiac function in patients with heart failure and reduces infarct size after ischemia/reperfusion injury in the heart. However, little attention has been paid for the endogenous regulatory mechanisms regulating EpoR expression. In this study, we hypothesize that B-type natriuretic peptide upregulates EpoR gene expression in failing heart.

Methods and Results:
Wister rats underwent transverse aortic constriction surgery to induce hypertrophy. RT-PCR analyses of those rats showed that EpoR mRNA levels were increased in the left ventricle and positively correlated with the levels of BNP mRNA (n=10, r=0.67, p<0.05). Next we examined the expression of EpoR in human failing heart by using autopsy specimens and found that EpoR mRNA levels were significantly elevated in patients with dilated cardiomyopathy compared with those in normal heart. Immunohistochemistry of endomyocardial biopsy specimens of failing heart (n=54) showed that EpoR mRNA levels were correlated with severity of cardiac dysfunction estimated by diameter of cardiac chambers, pathomorphology, serum BNP concentration and functional class of New York Heart Association. Interestingly, stimulation of cultured neonatal rat cardiac myocytes with BNP, but not with hypertrophic reagents including endothelin I, angiotensin II and norepinephrine, significantly increased the EpoR mRNA levels in a time-dependent manner. Overexpression of cGMP-dependent protein kinase (PKG) increased EpoR transcript in cultured cardiac myocytes. BNP-induced EpoR expression was abrogated in the presence of KT5823, a specific inhibitor for PKG.

Conclusion:
These results suggest a role for BNP in mediating an induction of EpoR expression in failing myocardium and indicate that the cardiac EpoR gene is a target of cGMP/PKG signaling.
Abstract 2424: Improvement Of Cardiopulmonary Exercise Capacity In Patients With Chronic Post-infarction Heart Failure (CHF) After Intracoronary Infusion Of Bone Marrow-derived Progenitor Cells (BMC)
Authors: Honold Joerg , Geiger Lenka , Fischer-Rasokat Ulrich , Assmus Birgit , Schaechinger Volker , Spyridopoulos Ioakim , Zeiher Andreas M
Published: July 2021

Intracoronary (i.c.) infusion of BMC in patients (pts.) with CHF is associated with improvements in left ventricular ejection fraction (LVEF) and reduction of NT-proBNP serum-levels, especially in pts. with more severe heart failure. However, ist is unknown whether the modest improvements in cardiac function translate into an increase in cardiopulmonary exercise capacity. A total of 52 CHF-pts. performed cardiopulmonary exercise tests (CPET) according to a modified Bruce protocol before and 3 months after i.c. infusion of BMC into the infarct-related artery. Anaerobic threshold (AT) was determined by the v-slope method. Overall, pts. were 58±12 years old with a moderately impaired LVEF (mean 42±11%) and a median NYHA-class 2±0.75. NT-proBNP-serum levels were elevated (1007±154 pmol/ml). All pts. received chronic optimized medical therapy with betablockers, ACE-inhibitors and combined diuretics, which was kept constant during the study duration. Initial CPET revealed reduced peak oxygen uptake (peak VO2: 14.0 ml/min/kg), maximal oxygen Pulse (O2Pmax: 11.4 ml/beat) and oxygen uptake at AT (VO2AT: 10.9 ml/min/kg), whereas CO2-equivalents (EqCO2) were elevated (29.7). 3 months after therapy, repeated CPET showed an increase in peak VO2 (14.0±3.9 to 15.3±4.3 ml/min/kg, p=0.07), whereas VO2 AT (10.8±2.5 to 10.8±2.5 ml/min/kg, p= n.s.), O2Pmax (11.2 ± 3.1 to 12.0±3.3 ml/beat, p= n.s.) or EqCO2 (29.7±6.4 to 29.8±6.8, p= n.s.) remained unchanged. However, after dichotomizating the patient cohort according to the median of VO2max at baseline, pts. with lower initial VO2max showed a significant improvement in VO2max (12.8±1.5 to 13.5±2.7ml/min/kg, p= 0.03) and an improvement in VO2AT (9.1±1.8 to 9.5±2.2 ml/min/kg, p= ns), as well as a reduction of EqCO2 (34.7±7.1 to 33.8±8.0, p= ns). In contrast, pts. with initial VO2max > median did not show any significant improvements. These findings indicate that intracoronary BMC-therapy improves exercise capacity in CHF-patients with more advanced heart failure. Therefore, cardiopulmonary exercise testing might help to identify pts. more likely to derive functional benefit from intracoronary BMC administration.
Abstract 2455: Short Sleep Duration is an Independent Predictor of Cardiovascular Events in Hypertensive Patients
Authors: Eguchi Kazuo , Pickering Thomas G , Schwartz Joseph E , Hoshide Satoshi , Ishikawa Joji , Shimada Kazuyuki , Kario Kazuomi
Published: July 2021

We aimed this study to test the hypothesis that short duration of sleep is independently associated with incident cardiovascular diseases (CVD) in hypertensive patients. We performed ambulatory BP monitoring (ABPM) in 1255 subjects with hypertension (mean age: 70.4 ± 9.9 years) and they were followed for an average of 50 ± 23 months. Short sleep duration was defined as <7.5 hrs (20
th
percentile). Multivariable Cox hazard models predicting CVD events were used to estimate the adjusted hazard ratio (HR) and 95% CI for short sleep duration. A riser pattern was defined when average nighttime SBP exceeded daytime SBP. The end point was cardiovascular events: stroke, fatal or non-fatal myocardial infarction (MI), and sudden cardiac death. In multivariable analyses, short duration of sleep (<7.5 hrs) was associated with incident CVD (HR=1.68; 1.06 –2.66, P=.03). A synergistic interaction was observed between short sleep duration and the riser pattern (P=.089). When subjects were categorized on the basis of their sleep time and riser/non-riser patterns, the shorter sleep+riser group had a highest incidence of CVD among the 4 groups (
Figure
), and substantially and significantly higher incidence of CVD than the predominant normal sleep+non-riser group (HR=4.43; 2.09 –9.39, P<0.001), independent of covariates. Short duration of sleep is associated with incident CVD risk, and the combination of riser pattern and short duration of sleep that is most strongly predictive of future CVD, independent of ambulatory BP levels. Physicians should inquire about sleep duration in the risk assessment of hypertensive patients.
Abstract 2462: Obstructive Sleep Apnea Treatment Improves the Blood Pressure Behavior in Normotensive Patients: A Randomized Study
Authors: Drager Luciano F , Diniz Patrícia M , Diegues-Silva Luzia , Couto Roberta B , Pedrosa Rodrigo P , Marcondes Bianca , Giorgi Dante M , Krieger Eduardo M , Lorenzi-Filho Geraldo
Published: July 2021

Introduction:
Obstructive sleep apnea (OSA) promotes significant alterations on blood pressure during sleep. In patients with concomitant hypertension, the treatment with continuous positive airway pressure (CPAP) promotes significant reductions on blood pressure. However, the impact of CPAP on 24 hour blood pressure in normotensive patients is poorly understood.

Methods:
We included 22 apparently healthy patients with severe OSA defined by polysomnography (apnea/hypopnea index (AHI) >30 events/hour). We excluded hypertension according current guidelines by office measurements. They were randomized to no treatment (control) or CPAP for 3 months. At baseline and at the end of the protocol, we performed 24 hour blood pressure (BP) monitoring evaluating daytime and nighttime BP as well as the morning surge (average of systolic BP during the 2 hours after awakening minus the average of systolic BP during the 1 hour that included the lowest nighttime BP) and highest systolic nighttime BP (mean of 3 BP measurements, centered on the highest nighttime reading).

Results:
After 3 months, patients randomized to CPAP (mean CPAP usage: 6 hours) presented a significant reduction on daytime (80.3±6.3 to 75.3±6.9 mmHg; P=0.02) and nighttime diastolic BP (67.8±9.5 to 61.4±7.5 mmHg; P=0.03). In addition, we observed a significant reduction on highest nighttime systolic BP (120.0±13.6 to 112.0±.9 mmHg; P=0.02) with a trend for a reduction on morning surge (22.3±9.2 to 17.3±.4 mmHg; P=0.08). No significant alterations occurred in the control group.

Conclusion:
Even in the absence of established hypertension, CPAP therapy improved the behavior of 24 hour BP in patients with severe OSA.
Abstract 2469: Circadian Blood Pressure Variation and Left Atrium Size in the Early Stages of Essential Hypertension: The Role of Pulse Pressure and Nocturnal Blood Pressure Fall
Authors: Taxiarchou Efstathios , Tsioufis Costas , Tsiachris Dimitris , Syrseloudis Dimitris , Giatrakos Ioannis , Tousoulis Dimitris , Kallikazaros Ioannis , Stefanadis Christodoulos
Published: July 2021

Introduction:
Left atrial (LA) enlargement is a common finding in hypertensive patients and might be an index for future adverse cardiovascular events. Similarly, increased pulse pressure (PP) as well as absence of nocturnal blood pressure (BP) fall is associated with unfavourable outcome in this setting.

Hypothesis:
Ambulatory BP parameters may be correlated with LA size in essential hypertension.

Methods:
332 consecutive, newly diagnosed subjects (aged 52±10 years), with untreated stage I–II essential hypertension [office BP =152/98 mmHg] were classified according to their nocturnal BP fall on 24-hour ambulatory BP monitoring to non-dippers (those with<10% nocturnal systolic and diastolic BP fall, n=194) and dippers (the remaining subjects, n=138). All subjects underwent complete echocardiographic study and LA volume was indexed for body surface area to estimate LA volume index (LAVI).

Results:
Non-dippers compared to dippers did not differ regarding age, sex, office BP and biochemical profile (p=NS for all cases). However, non-dippers compared to dippers had significantly increased 24-h systolic BP (138±14 vs 135±11 mmHg, p<0.05), 24-h pulse pressure (PP) (53±9 vs 51±8 mmHg, p<0.05) and night PP (53±10 vs 47±8 mmHg, p<0.001) as well as left ventricular mass index (108±28 vs 101±26 gr/m
2
, p<0.05) and relative wall thickness (0.44±0.07 vs 0.42±0.07, p<0.05), while they did not differ regarding LA diameter (3.95±0.39 vs 3.86±0.39 cm, p=NS) and LAVI (24.1±6.3 vs 23.5±6.1 ml/m
2
, p=NS). In the entire population LA diameter and LAVI exhibited positive relationships with 24-h PP (r=0.153, p=0.005 and r=0.251, p<0.001, respectively), day PP (r=0.150, p<0.01 and r=0.256, p<0.001, respectively) and night PP (r=0.148, p<0.01 and r=0.234, p<0.001, respectively). Multiple regression analysis models revealed that among components of ambulatory BP, only 24-h day PP was an independent predictor of LAVI (β=0.256, p<0.001).

Conclusions:
Ambulatory PP and particularly day PP but not circadian BP variation seems to determine the LA enlargement in hypertensive patients. Whether the abovementioned association contributes to the high cardiovascular risk observed in patients with wider day PP remains to be determined in future studies.
Abstract 2510: Culprit Lesion Remodeling Affects Long-Term Clinical Outcome in Patients with Acute Coronary Syndrome: A Prospective, Multicenter Three-Vessel Intravascular Ultrasound Study
Authors: Okura Hiroyuki , Taguchi Haruyuki , Kobayashi Yoshio , Sumitsuji Satoru , Terashima Mitsuyasu , Kataoka Toru , Masutani Motomaru , Ohyanagi Mitsumasa , Shimada Kenei , Yasuga Yuji , Takeda Yoshihiro , Ohashi Yoshitaka , Awano Kojiro , Fujii Kenichi , Mintz Gary S
Published: July 2021

Single center studies have shown that plaque rupture and positive remodeling are prognostic predictors of acute coronary syndrome (ACS). A total of 119 patients with first ACS events were enrolled in a multicenter, prospective, 3-vessel intravascular ultrasound (IVUS) registry. Pre-intervention IVUS imaging was performed in 98 patients. Remodeling index was defined as lesion site external elastic membrane cross sectional area (EEM CSA) divided by the proximal reference. Arterial remodeling was defined as either positive (PR; remodeling index >1.05) or intermediate/negative (IR/NR; remodeling index <1.05). Plaque rupture was a cavity that communicated with the lumen with an overlying residual fibrous cap fragment. Major adverse cardiac events (MACE) were death, myocardial infarction (MI), and target lesion revascularization (TLR). During follow-up (mean 3 years), 20 TLR events and 5 deaths were documented; but recurrent MI was not observed. Patients with PR had significantly lower MACE-free survival than patients with IR/NR (Log rank, p=0.03). Similarly, patients with plaque rupture showed a non-significant trend toward lower MACE-free survival (Log rank, p=0.13). By multivariate logistic regression analysis, culprit lesion PR was the only independent predictor of follow-up MACE. Culprit lesion remodeling is a strong predictor of long-term clinical outcome in patients with ACS.
Abstract 2513: Assessment of Both Coronary Microvascular Damage and Epicardial Flow Velocity Measurement Immediately after Successful Percutaneous Coronary Intervention for Acute Myocardial Infarction Predicts In-Hospital Complications and Survival
Authors: Yamamuro Atsushi , Akasaka Takashi , Kaji Shuichiro , Tamita Koichi , Katayama Minako , Kinoshita Makoto , Ehara Natsuhiko , Kobori Atsushi , Kitai Takeshi , Yamane Takafumi , An Yoshimori , Kim Kite , Funakoshi Syunsuke , Kimura Noriyuki , Tani Tomoko , Tanabe Kazuaki , Morioka Shigefumi , Furukawa Yutaka
Published: July 2021

Quantitative measurement of post-reperfusion epicardial flow velocity by a Doppler guidewire can predict clinical cardiac events in patients with acute myocardial infarction (AMI). It has also been reported that the coronary flow velocity pattern in patients with microvascular dysfunction is characterized by the presence of early systolic retrograde flow and a rapid diastolic deceleration time (DDT). The purpose of this study was to examine the role of assessing both epicardial flow velocity and microvascular damage in the prediction of in-hospital complications and survival after percutaneous coronary intervention (PCI). Two hundred and eleven consecutive patients with first anterior AMI who underwent successful PCI were subjected to coronary flow measurement immediately after successful PCI with a Doppler guidewire. The coronary flow velocity spectrum provided the following parameters: time-averaged peak velocity (cm/s, APV), systolic peak velocity (cm/s) and DDT (ms). We defined the presence of microvascular dysfunction as DDT ≤600 ms and the presence of systolic flow reversal, and slow epicardial flow as resting APV ≤10cm/s. We classified the patients into three categories: without microvascular dysfunction (group 1, n=122), with microvascular dysfunction and normal epicardial flow (group 2, n= 54), with microvascular dysfunction and slow epicardial flow (group 3, n=35). The clinical event rate was compared among the 3 groups. The in-hospital event rates for congestive heart failure, cardiac rupture and death were highest in group 3 and lowest in group 1 (Table

). Assessment of both coronary microvascular damage and epicardial flow velocity can accurately predict in-hospital complications and survival in AMI patients who underwent successful reperfusion of the infarct-related coronary artery, identifying a subset of high risk patients. In-hospital event rates (%)
Abstract 2531: Sirolimus-Eluting Stents Compared to Bare Metal Stents in Patients with Diabetes Mellitus: Patient-Level Meta-Analysis of Randomized Trials
Authors: de Waha Antoinette , Dibra Alban , Schömig Albert , Kastrati Adnan
Published: July 2021

Although it is widely believed that patients with diabetes mellitus obtain the greatest benefit from sirolimus-eluting stent, the evidence on the efficacy and safety of stents of this nature is limited. We performed a meta-analysis based on individual patient data from 4 randomized trials (586 patients) comparing sirolimus-eluting with bare metal stents (mean follow-up interval between 12 and 24 months). The primary efficacy endpoint was the need of reintervention. The primary safety endpoint was all-cause mortality. Myocardial infarction and stent thrombosis rates were also evaluated. There was a significant reduction in the overall hazard of repeat revascularization (HR 0.21, 95% confidence interval [CI] 0.13 to 0.33, P<0.001) with the use of sirolimus-eluting stents. Conversely, the overall hazard of death (HR 1.25, 95% CI 0.53 to 2.97, P=0.61) was not significantly different for patients receiving sirolimus-eluting stents compared to bare metal stents. Similarly, the overall hazard of stent thrombosis (HR 0.49, 95% CI 0.10 to 2.31, P=0.37) and myocardial infarction (HR 0.69, 95% CI 0.36 to 1.31, P=0.26) were comparable among patients treated with sirolimus-eluting or bare metal stents. No evidence of heterogeneity was observed across the trials regarding all endpoints. Use of sirolimus-eluting stents in patients with coronary artery disease and diabetes mellitus is highly effective and safe.
Abstract 2562: Two-Year Clinical Follow-Up of COREA-TAXUS Trial: Long-Term Safety And Efficacy of Celecoxib for 6 Months After Paclitaxel-Eluting Stents Implantation
Authors: Chung Jin-Wook , Yang Han-Mo , Kwon Dong-A , Suh Jung-Won , Park Kyung-Woo , Cho Hyun-Jai , Kim Sang-Hyun , Kim Cheol-Ho , Oh Byung-Hee , Park Young-Bae
Published: July 2021

Background: The effect of celecoxib on restenosis after angioplasty with a Taxus stent (COREA-TAXUS) trial is an open-label randomized controlled study, where we reported celecoxib was effective in reducing 6months late loss of Taxus stent. With this cohort, we analyzed long-term clinical outcomes.

Method: Two hundred sixty seven patients underwent successful paclitaxel-eluting stents implantation for native coronary lesions. Patients were randomized to receive celecoxib (400 mg before the intervention, and 200 mg twice daily for 6 months after the procedure) or not. Clinical endpoints were cardiac death, non-fatal myocardial infarction, and revascularization of the target lesion.

Results: At 6 months, frequency of adverse cardiac events was significantly lower in the celecoxib group (5.3% versus 16.2%, P=0.005), mainly because of reduced need for revascularization of the target lesion (5.3% versus 15.4%, P=0.009). Between 6 and 24 months, frequency of adverse cardiac events was not different between the celecoxib group and the control group (1.6% versus 4.4%, P=NS: 0% versus 0% for cardiac death; 0.8% versus 0.9% for non-fatal myocardial infarction; 0.8% versus 3.5% for revascularization of target lesion, P=all NS). At 2 years, frequency of adverse cardiac events was still significantly lower in the celecoxib group (6.9% versus 19.9%, P=0.002)

Conclusion: In the COREA-TAXUS trial, the adjunctive use of celecoxib for 6 months after Taxus stent implantation was safe and clinically effective for 2 years.
Abstract 2612: Immediate Clinical And Hemodynamic Benefits Of Restoration Of Pulmonary Valvar Competence In Patients With Pulmonary Hypertension
Authors: Lurz Philipp , Nordmeyer Johannes , Coats Louise , Taylor Andrew M , Bonhoeffer Philipp , Schulze-Neick Ingram
Published: July 2021

Background: In patients with severe pulmonary hypertension (PH), chronic pressure overload leads to right heart failure, the main reason for clinical deterioration and mortality. In the presence of pulmonary regurgitation (PR), right ventricular (RV) efficiency and cardiac output are further compromised. Therapeutic options in this patient group are limited due to the high risk of open-heart surgery in the presence of the PH. Percutaneous pulmonary valve implantation (PPVI) may offer a new treatment option for relief of PR without the risk of cardiopulmonary bypass.

Methods: Between April 2004 to December 2007, 7 patients with PH (mean PAP > 25 mmHg) due to congenital heart disease and severe PR underwent PPVI. Patients were assigned to New York Heart Association (NYHA) functional classes I – IV. Resting peripheral oxygen saturations were measured. Trans-thoracic echocardiography and magnetic resonance imaging before and after valve implantation was performed.

Results: The valve implantation procedure was feasible and uncomplicated in all 7 cases, successfully abolishing PR. There was a significant increase in diastolic (15.4±7.3 to 34.0±8.5 mmHg; p=0.007) and mean (29.7±8.1 to 41.3±12.9 mmHg; p=0.034) pulmonary artery pressures, and an improvement in NYHA functional class (from median IV to median III; p<0.008). Peripheral oxygen saturations rose from 85.9±11.0% to 91.7±8.3% (p=0.036). RV end-diastolic volumes decreased (from 157.0±44.7 to 140.3±53.3 ml/m
2
), whilst effective RV stroke volume increased (from 23.4±9.3 to 41.0±11.6 ml/m
2
). During a median follow-up of 20.3 months (range 1.3 – 47.5), competence of the bovine jugular venous valve was well maintained despite near systemic pulmonary pressures. None of the devices were explanted during follow-up.

Conclusion: Trans-catheter abolishment of PR in patients with PH is well tolerated and leads to clinical and haemodynamic improvement, most likely due to a combination of increased pulmonary perfusion pressures and RV efficiency. These findings emphasize the detrimental effects of volume overload in chronically pressure overloaded right ventricles.
Abstract 2656: Copeptin Predicts Cardiovascular Death in STEMI Independent of Clinical Factors and NT-proBNP
Authors: Desai Nihar R , Morrow David A , Jiang Songtao , Bode Christoph , Rifai Nader , Cannon Christopher P , Gerszten Robert E , Sabatine Marc S
Published: July 2021

Background
: Elevated levels of copeptin, the c-terminal portion of provasopressin, add significantly to natriuretic peptides for mortality prediction in heart failure. We hypothesized that elevated levels would predict mortality in ST-elevation myocardial infarction (STEMI).

Methods
: Circulating copeptin levels were measured at baseline in a case-cohort of 535 STEMI patients undergoing fibrinolysis in CLARITY-TIMI 28. Patients were stratified into quartiles by baseline copeptin. Multivariable logistic regression was used to examine the association between copeptin and 30-d cardiovascular (CV) mortality independent of clinical factors and NT-proBNP.

Results
: The median level of copeptin was 615 pg/ml (IQR 333–728 pg/ml). Baseline levels of copeptin tended to be higher in patients who were older, had a prior MI, were treated sooner after sx onset, and were in Killip class II-IV. For each 1-SD increase in log-transformed copeptin, the OR for CV death was 1.45 (p=0.01). After adjusting for differences in baseline characteristics patients in the highest copeptin quartile were at a significantly higher risk of CV death compared with patients in quartiles 1–3 (OR 1.99 [1.05–3.78]). Copeptin was not significantly correlated with NT-proBNP (r=0.09). In a multivariable model, copeptin and NT-proBNP were each significant independent predictors of CV death (Figure

); the c-statistic went from 0.75 to 0.81 with their addition to a model containing clinical risk factors.

Conclusion
: In a multimarker model, circulating levels of copeptin and NT-proBNP at presentation were powerful and complementary predictors of CV death beyond traditional risk factors in patients with STEMI.
Abstract 2722: Poor Heart Failure Self-Care is a Worldwide Problem
Authors: Riegel Barbara , Driscoll Andrea , Suwanno Jom , Moser Debra K , Dickson Victoria V , Carlson Beverly , Cameron Jan
Published: July 2021

Heart failure (HF) is reaching epidemic proportions across the world. Self-care, an integral component of therapy, is known to be poor in the US but little is known about self-care in other populations. In a descriptive, comparative study, 6 samples (2,082 adults) were drawn from 4 ethnically/culturally diverse locations in Australia, Thailand, and the US (blacks and whites in the northeast; Hispanics from the southwest). All investigators used the same general inclusion and exclusion criteria. All patients had a diagnosis of chronic HF objectively confirmed and all resided in a private residence where self-care was a reasonable expectation. Self-care was measured using carefully translated versions of the Self-Care of HF Index (SCHFI), which provided scores on self-care maintenance, management, and confidence. Data were integrated and analyzed using multivariate analysis after demographic (education), clinical (NYHA, newness of diagnosis), and treatment (participation in disease management) differences were controlled. When adequate self-care was defined as a standardized score ≥70%, self-care was inadequate in most categories in most groups (Figure

). After adjusting mean scores with covariates, group differences were still evident, with self-care maintenance lowest in the Thai and Hispanic samples (p<.001), management and confidence lowest in the Thai sample (p< .001), and confidence highest in the Hispanic sample (p<.001). Self-care was poor in all of the samples. Intervention studies aimed at improving self-care are greatly needed in all the countries studied.
Abstract 2764: Clinical Phenotype of Japanese LQT3 Form of Congenital Long QT Syndrome by Location of Mutation from Japanese Multicenter Registry
Authors: Yamagata Kenichiro , Horie Minoru , Ogawa Satoshi , Aizawa Yoshifusa , Ohe Tohru , Yamagishi Masakazu , Makita Naomasa , Tanaka Toshihiro , Akao Masaharu , Yoshinaga Masao , Okamura Hideo , Noda Takashi , Miyamoto Yoshihiro , Kamakura Shiro , Shimizu Wataru
Published: July 2021

Background:

Effects of location of mutation on clinical phenotype in a large scale of patients with LQT3 syndrome are unclear.

Methods and Results:

Forty-nine patients (male=30, proband=25) with an
SCN5A
mutation were retrospectively studied from a Japanese multicenter registry and divided into patients with mutations located in the transmembrane (TM) portion and the non-transmembrane (non-TM) portion. Although there was no significant difference in the QTc interval between the two groups (478±78 vs. 508±37ms; p=0.079), both cumulative cardiac event rates and lethal cardiac event (VF and/or aborted cardiac arrest) rates were significantly higher in the TM group (Figure

, p=0.006, p=0.007, respectively). By performing the multivariate analysis, longer QTc interval and the TM group was an independent risk factor for cardiac events (QTc≥500ms vs. QTc<500ms; hazard ratio=5.612, p=0.05, TM vs. non-TM; hazard ratio=15.234, p=0.009).

Conclusion:

In this multicenter study, Japanese LQT3 patients with mutations located in the transmembrane portion were at higher risk for cardiac events.
Abstract 2821: Does End-systolic Stress Adequately Reflect Time-varying Left Ventricular Wall And Fiber Stress in Hypertension?: Influence Of The Components Of Arterial Pulsatile Load
Authors: Chirinos Julio A , Segers Patrick , Swillens Abigail , Kirkpatrick James , Rahmouni Hind , Lanning Craig , Silvestry Frank , Keane Martin , Wiegers Susan , Ferrari Victor , Sutton Martin St John
Published: July 2021

Pulsatile hemodynamic abnormalities are key determinants of left ventricular (LV) afterload, which is commonly assessed by end-systolic wall and fiber stress. These important indices of afterload are highly sensitive to cavity size and wall thickness. Since cavity size, pressure and wall thickness all change markedly throughout systole, end-systolic stress may not adequately describe the contribution of different components of arterial load to time-varying stress, since these arterial components also vary markedly throughout systole. We studied 25 hypertensive adults (mean age: 58 yrs; 44% male). Central pressure (carotid tonometry) and flow (Doppler echocardiography) were measured simultaneously and the pressure wave was decomposed into its forward (Pf) and reflected (backward, Pb) components. Speckle-tracking echocardiography was used to measure instantaneous LV cavity and wall areas during systole, which were used to compute time-varying fiber (Arts method) and meridional wall (Janz method) stress. Peak fiber and wall stress values were, on average, 1.87- and 2.19-fold higher than end-systolic values, respectively. Peak fiber and wall stress occurred in early systole (97±7 and 81±4 msec after the onset of ejection, respectively), before important contributions of Pb to central pressure. Although end-systolic stress predicted a large proportion of the variability in peak fiber (76%; p<0.0001) and wall (80%; p<0.0001) stress, the ratio of peak/end-systolic stress decreased with increasing Pb/Pf amplitude ratio (fiber stress: R=−0.59, p=0.001; wall stress: R=−0.50; p=0.01). Similarly, the ratio of mean systolic/end-systolic stress decreased with increasing Pb/Pf amplitude ratio (fiber stress: R=−0.58, p=0.002; wall stress: R=−0.51; p=0.007). Adjustment for systemic vascular resistance did not affect these results. The relationship between end-systolic and time-varying LV fiber and wall stress is strongly biased by wave reflections. End-systolic stress does not adequately reflect the contribution of different components of arterial load on time-varying stress, which should be assessed with the combination of arterial tonometry and contemporary echocardiographic techniques.
Abstract 2835: Non-Cardiac Findings on Cardiovascular Magnetic Resonance Imaging Are Common: Impact of Imaging Sequences and Reading Session Format
Authors: Romney Benjamin P , Khosa Faisal , Costa Daniel N , Chan Peter , Rofsky Neil M , Manning Warren J
Published: July 2021

Purpose The true prevalence of non-cardiac pathology on clinical cardiovascular magnetic resonance (CMR) imaging is not fully defined. While prior studies have shown few non-cardiac findings (NCFs) on CMR reports, this may be an underestimate. We sought to determine the prevalence of NCFs by using a second imaging review with specific attention to NCFs.

Materials and Methods The images from all 495 clinical CMR studies performed at our center in 2006 were independently reviewed by a radiologist for the presence of NCFs, defined as benign (e.g., pleural effusion, hiatal hernia), indeterminate (e.g. pleural effusion, enlarged lymph node), or worrisome (e.g. lung nodule, aortic dissection). Data were compared with NCFs listed in the subject’s clinical CMR report, which also included information as to whether a radiologist was physically present at the original reading session.

Results The initial clinical CMR reports included 105 NCFs (30 benign, 68 indeterminate, and 7 worrisome). On focused image review, 295 NCFs (144 [49%] benign, 137 [46%] indeterminate, 14 [5%] worrisome) were identified in 212/495 (43%) studies, with 113 studies (23%) containing indeterminate and/or worrisome NCFs. The vast majority (281/295, 95%) of NCFs were visible on either the initial scout images (186/295, 63%) or thoracic T1w axial fast spin echo images (176/295, 60%). Overall, 36% (105/295) of NCFs (21% of benign, 50% of indeterminate, and 50% of worrisome) detected on our image review were included in the original clinical CMR report. NCFs were reported more frequently when a radiologist was present for the joint CMR readout (42% 95/228;vs. 15% 10/67;, p=0.003).

Conclusion Indeterminate or worrisome NCFs are more common than previously reported, and involve nearly a quarter of clinical CMR studies. The vast majority of NCFs were visible on scout and T1w axial images. A joint reading session with cardiologists and radiologists improves the detection and reporting of NCFs. These data also highlight the importance of training CMR practitioners to identify NCFs.
Abstract 2868: Long-Term Prognostic Predictors of Isolated Significant Tricuspid Regurgitation
Authors: Lee Jeong-Woo , Song Jong-Min , Lee Jae Won , Yi Myung-Zoon , Jin Eun Sun , Kang Duk-Hyun , Song Jae-Kwan
Published: July 2021

Background:
Long-term outcomes of isolated significant tricuspid regurgitation (TR) without significant left-side heart disease remain to be clearly demonstrated.

Methods:
We enrolled 547 consecutive patients (age: 64 ± 14 years) with isolated significant TR. The patients with atrial septal defect, significant pulmonary or pulmonary vascular disease, right ventricular dysplasia and constrictive pericarditis were excluded. Initial clinical and echocardiographic characteristics and clinical outcomes were analyzed for 5.6 ± 2.1 years.

Results:
Survival rate was not different between 39 patients who underwent tricuspid valve (TV) surgery and 508 patients who did not (p=0.48). Of 508 patients without TV surgery, 32 patients (6.3%) died with cardiac cause during the follow-up period. Those patients were older (71 ± 16 vs. 64 ± 13 years, p<0.05) and showed initial larger TR jet area (15 ± 7 vs. 12 ± 4 cm
2
, p<0.05), and higher pulmonary artery systolic pressure (PASP, 46 ± 22 vs. 39 ± 16 mmHg, p<0.05). By adjusting other baseline characteristics using Cox proportional hazard model, age (HR; 1.045, 95% CI: 1.013 – 1.078), initial TR jet area (HR; 1.110, 95% CI; 1.061 – 1.160), and PASP (HR; 1.025, 95% CI; 1.009 – 1.042) were independent predictors of cardiac mortality. Mortality rates did not differ between patients with organic and functional TR. Initial TR jet area ≥12 cm
2
and PASP ≥36 mmHg were best cut-off values for predicting cardiac mortality (Figure

).

Conclusions:
Severity of TR and pulmonary hypertension are prognostic factors independent of age in medically-managed patients with isolated significant TR. The results may suggest an optimal surgical timing in these patients.
Abstract 2876: Early Retention and Subsequent Engraftment of Transplanted Progenitor Cells is Improved by Delivery within Collagen Matrix
Authors: Zhang Yan , Lamoureux Marc , Thorn Stephanie , Chan Vincent , Price Joel , Beanlands Robert B , DaSilva Jean N , deKemp Robert A , Suuronen Erik J , Ruel Marc
Published: July 2021

Background:
To investigate the mechanisms involved in the potentiation of cell therapy by delivery matrices, we evaluated the retention and engraftment of transplanted human circulating progenitor cells (CPCs) injected in a collagen matrix by using
in vivo
positron emission tomography (PET) imaging,
ex vivo
biodistribution, and immunohistochemistry.

Methods:
CPCs were labeled with
18
F-FDG and injected with or without a collagen type I-based matrix in the ischemic hindlimb muscle (IM) of rats (2x10
6
cells; n=15/group). Localization of cells was acquired by PET imaging (15 min) at 150 min post-injection. In addition, radionuclide biodistribution, immunofluorescence, and immunohistochemical examination of transplanted CPCs were performed at up to 14 days.

Results:
Cell labeling efficiency was CPC-concentration dependent (r=0.61,
p
<0.001), but not
18
F-FDG-dose dependent. Labeled CPCs exhibited excellent short-term stability and viability. Persistence of
18
F-FDG radioactivity in cells was markedly greater than non-specific retention in the matrix. Wholebody (WB) PET images revealed better CPC retention in the IM and less non-specific leakage to other tissues when CPCs were delivered within the matrix (IM/WB retention ratio of 43.9±8.2%), compared to cells injected alone (22.3±10.4%;
p
=0.040) and to
18
F-FDG injected with or without the matrix (9.7±5.5% and 11.0±5.5%, respectively;
p
<0.005). Radioactivity biodistribution confirmed that accumulation was increased (by 92.5%;
p
=0.024) in the IM and reduced (by 1.1 to 23.8%;
p
<0.05) in non-specific tissues when cells were injected within the matrix, compared to cells injected alone. Anti-human mitochondria staining showed increased cell retention in the IM with use of matrices (3.0±2.1%) versus cells only (1.9±0.8%;
p
=0.048). At 14 days the number of CD31
+
transplanted human cells was greater (1.6±0.1%) when injected within the matrix than injected alone (0.7±0.1%;
p
=0.004).

Conclusions:
Collagen-based delivery matrices improve the early retention of transplanted CPCs, which in turn favors subsequent cell engraftment in the ischemic tissue. This mechanism conferred by the matrix has potential implications for the optimization of cell therapy at the early stages after cell delivery.
Abstract 2950: Distinct Regulation of Cardiac Function by Histone Deacetylase Inhibitors in Response to Pressure Overload
Authors: Ma Jing , Minamino Tetsuo , Asano Yoshihiro , Liao Yulin , Kitakaze Masafumi , Wang Shiwen
Published: July 2021

Background-
Recent work has uncovered that histone acetylation might work as a nodal control point in the complex signal network for gene regulation in hypertrophic myocardium, moreover, histone deacetylase (HDAC)inhibitors might hold promise as potential therapeutic agents in hypertrophic heart disease. In this study, we tested the effects of some HDAC inhibitors on hypertrophy and subsequent cardiac dysfunction in response to pressure overload.

Method and results-
Transverse aortic constriction (TAC) operation were performed on C57BL/6J mice and pressure overload was successfully produced. Cardiac hypertrophy and dysfunction induced by TAC for 6 weeks were significantly blunted by trichostatin A (TSA) and valproic acid (VPA). In contrast, treatment by 4-Sodium phenylbutyrate (4-PBA) unexpectedly further exaggerated cardiac remodeling at week 6 compared with vehicle-treated mice, indicated by larger ratio of heart weight to body weight, bigger cross-sectional area and more enlarged left ventricle (LV) dimension. 4-PBA also led to lower ejection fraction and fractional shortening. Moreover, invasive hemodynamic measurements showed significantly higher LV end diastolic pressure (31.0 vs 15.5 mmHg, p<0.001) and lower contractivity index (120.8 vs 160.4, p<0.01) compared with vehicle-treated mice, suggesting the deterioration of diastolic and systolic function. In accordance with these data, the expressions of hypertrophic markers were further increased by 4-PBA administration. Kaplan-Meier analysis revealed significantly lower survival rate in 4-PBA-treated mice (32.7% vs 66.7%, p<0.001). Similarly, treatment with butyrate acid (BS), an analogue of 4-PBA, also achieved unbeneficial effect. All the 4 HDAC inhibitors successfully inhibited HDAC total activity
in vivo
and
in vitro
. Individual HDAC activity assay showed rather than class IIa members (HDAC 4 and 7), 4-PBA and BS predominantly inhibit class IHDACs (HDAC2 and 8), whereas VPA and TSA inhibit them all to a similar extent.

Conclusion-
Together, these data suggest that 4-PBA and BS accelerate load -induced hypertrophy and cardiac dysfunction, whereas VPA and TSA hold opposing effects. The distinct regulation might be due to differential selectivity on certain HDAC subtypes.
Abstract 2959: Granulocyte-Colony Stimulating Factor Therapy is Associated with Reduced Incidence of Acute Rejections and Allograft Vasculopathy in Heart Transplant Recipients
Authors: Haddad Francois , Vrtovec Bojan , Pham Michael , Deuse Tobias , Fearon William , Valantine Hannah , Hunt Sharon
Published: July 2021

Background.
Granulocyte-colony stimulating factor (G-CSF) has been shown to attenuate coronary disease in non-transplant population and decrease the incidence of acute rejections in experimental models of heart transplantation.

Hypothesis.
We hypothesized that G-CSF may decrease the incidence of allograft vasculopathy and rejection in heart transplant recipients.

Methods.
Of 247 patients who underwent heart transplantation at Stanford University Medical Center from 2000 to 2007 we enrolled 52 (21%) patients who presented with leukopenia (WBC < 2.5 x 10
9
cells/L) in the absence of active infection, rejection or malignancy. In 24 (46%) patients leukopenia was treated with G-CSF (mean dose 348 ± 78 mcg daily; G-CSF Group), and 28 (54%) patients received no G-CSF therapy (non-GCSF group). All patients were followed for 1 year after leukopenia occurence for the development of allograft vasculopathy (any new stenotic lesion on annual coronary angiography) and rejection incidence (ISHLT grade ≥3A or higher, or severe non-cellular rejection).

Results.
At baseline, G-CSF Group and non-G-CSF Group did not differ in age (54 ± 16 vs. 47 ± 14 years, respectively,
P
= 0.1), gender (male: 17% vs. 35%,
P
= 0.12), race (Caucasian: 79%, vs. 78%,
P
= 0.96), heart failure etiology (ischemic: 26% vs. 45%,
P
= 0.12), creatinine (1.6 ± 1.1 mg/dl vs. 1.5 ± 0.6 mg/dl,
P
= 0.6), LVEF (64 ± 8% vs. 64 ± 7%,
P
= 0.81), immunosupressive regimen (CyA/MMF/Prednisone: 42% vs. 54%,
P
= 0.4), or post-transplant time of leukopenia occurence (284 ± 396 days in the G-CSF Group vs. 347 ± 365 days in Controls,
P
= 0.57). During 1-year follow-up there were no events in the G-CSF Group, and 1 death in the non-G-CSF Group (
P
= 0.34). Rejection incidence was significantly lower in the G-CSF Group (8% vs. 36% in Controls,
P
= 0.019), as was cardiac allograft vasculopathy (4% vs. 29%,
P
= 0.02).

Conclusions.
G-CSF therapy appears to be associated with decreased incidence of acute rejections and allograft vasculopathy in heart transplant recipients, suggesting that G-CSF may have immunomodulatory effects.