bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12934: Stent Design Affects the Side Branch Orifice Area Following Coronary Bifurcation Stenting: Comparison Between Resolute Integrity versus Xience V Stent Using a Newly Developed OCT algorithm
Authors: Minami Yoshiyasu , Wang Zhao , Lee Stephen , Uemura Shiro , Soeda Tsunenari , Raffel Owen Christopher , Barlis Peter , Itoh Tomonori , Fujimoto James , Jang Ik-Kyung
Published: July 2021

Introduction:
Bifurcation lesions remain a challenge in interventional cardiology. Preservation of side branch (SB) orifice may be affected by plaque distribution, SB orifice geometry, and stent design. We compared the open areas of a SB for the two widely used drug-eluting stents, Resolute Integrity (ZES) and Xience V (EES), using a newly developed OCT algorithm.

Methods:
From our registry database, we identified 123 consecutive cases with bifurcation (SB diameter ≥2.0mm) treated with ZES or EES. Among them, 88 de novo cases (ZES n=46, EES n=42) treated with a single stent were included in the final analysis. In collaboration with MIT, a new algorithm was developed to reconstruct the en face view from raw OCT data to evaluate the SB orifice accurately. Using this new algorithm the SB orifice area (A) and the area obstructed by struts (B) were calculated. The study endpoint was the percent open area defined as (A-B) / A*100.

Results:
Of 88 cases, 31 (14 ZES and 17 EES) cases were treated with SB dilatation and 57 (32 ZES and 25 EES) cases were treated with crossover stenting without SB dilatation. In those cases with SB dilatation, the %open area was not significantly different between ZES and EES (median, 91.4% vs 89.0%, P=0.33). However, the %open area was significantly smaller in ZES than in EES (median, 84.3% vs 89.2%, P=0.04) in crossover stenting. Multivariate analysis showed that the use of ZES was an independent predictor for the smaller %open area (below median, odds ratio 4.38, P=0.03) in crossover stenting.

Conclusions:
Using this newly developed algorithm to reconstruct OCT image en face, we demonstrated that the %open area was significantly smaller in Resolute Integrity than that in Xience V in crossover stenting, whereas no significant difference was seen between the two stents after SB dilatation. This finding indicates that stent design affects the SB open area and post dilatation may be important after Resolute Integrity stent implantation.
Abstract 12938: Long-Term Mortality Benefit With Intracoronary Thrombus Aspiration Before Primary Percutaneous Coronary Intervention
Authors: Sardar Partha , Chatterjee Saurav , Singh Mandeep , Nairooz Ramez , Frankel Robert , Naidu Srihari S , Mukherjee Debabrata
Published: July 2021

Background:
Mortality benefit of routine intracoronary thrombus aspiration during primary percutaneous coronary intervention (PCI) has been questioned. The recent TASTE trial did not show a mortality benefit with thrombus aspiration at 1 month, however benefits from accompanying reductions in myocyte injury might accrue over time. A meta-analysis of randomized trials (RCTs) was performed to evaluate the effect of follow up duration on effectiveness of aspiration thrombectomy.

Methods:
PubMed, Cochrane Library, EMBASE, Web of Science and CINAHL databases were searched through March, 2014. We included RCTs with acute myocardial infarction (AMI) patients randomized to aspiration thrombectomy prior to primary PCI compared with conventional primary PCI alone. Two individuals reviewed the trials for inclusion and extracted data from the RCTs. We used random-effects models.

Results:
Data were pooled from 16 RCTs with 11,649 patients. All-cause mortality was significantly lower with aspiration thrombectomy after at least 12 months of follow up

(Odds ratio [OR] =0. 61; 95% CI 0.37-0.99; p=0. 05). Pooled data for other time frames, i.e in-hospital, 1 month, 6 month follow up, did not reach statistical significance.

Conclusion:
Beneficial effects of thrombus aspiration on mortality are not evident until 12 months post-procedure, consistent with the long-term effects of myocardial salvage. Subsequent trials evaluating thrombus removal should accordingly be powered for long-term mortality in addition to known procedural and angiographic endpoints.
Abstract 12946: Higher Burden of Atrial Fibrillation is Independently Associated With Lower Cognitive Function: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Chen Lin Y , Agarwal Sunil K , Lopez Faye L , Gottesman Rebecca F , Loehr Laura R , Soliman Elsayed Z , Mosley Thomas H , Folsom Aaron R , Coresh Josef , Alonso Alvaro
Published: July 2021

Background:
Atrial fibrillation (AF) is associated with greater cognitive decline and increased risk of dementia. However, it is unknown whether AF burden (% of time a person is in AF) is associated with cognition. We aimed to assess the cross-sectional association of AF burden with cognitive test scores in the ARIC study, a community-based prospective cohort study in the USA.

Methods:
We included 325 (mean age, 76.9 ± 5.2 years; 52.9% female) participants who underwent cognitive tests (Table) and ≥2 days of heart rhythm recording using the Zio
®
Patch (a non-invasive, leadless, 2-week continuous ECG recording device by iRhythm Techonologies, Inc.) in July 2013-March 2014. We used multivariable linear regression to assess the association of AF burden (dichotomized at the median) with standardized z-scores of cognitive tests.

Results:
The mean wear and analysis time of the Zio
®
Patch were 13.1 ± 2.1 and 12.7 ± 2.3 days, respectively. Of 325 participants, 13 (4.0%) had a prior ischemic stroke. There were 26 (8%) participants with AF recorded (median AF burden among participants with AF, 51%), of whom 4 (15.4%) had a prior ischemic stroke. Compared with absence of AF, higher AF burden was independently associated with lower MMSE, DWR, and AN scores, but not DSS and CTP.

Conclusions:
Higher burden of AF is independently associated with lower cognitive function, specifically memory and verbal function. This association needs to be confirmed prospectively and further research is needed to elucidate its mechanism.
Abstract 12972: Reduction of Unnecessary Radiation Exposure for Cardiovascular Patients by Adoption of a Stress-First Protocol for Nuclear-Based Cardiac Stress Testing
Authors: Russo Robert J , Allem Jordan , Costa Heather S , Silva Patricia D
Published: July 2021

Background:
In 2010, the FDA issued the Initiative to Reduce Unnecessary Radiation Exposure from Medical Imaging. The purpose of this study was to determine the total radiation exposure for cardiovascular patients and the relative contribution of nuclear-based cardiac stress testing.

Method:
The electronic medical record was reviewed to identify all patients who underwent cardiac stress testing in 1 institution over a 10-year period. The type and number of all radiation-based diagnostic tests were identified, and a hospital-determined or published radiation dose was used to calculate each patient’s gender-specific total annualized radiation exposure expressed in mSv. Therapeutic radiation-based procedures were excluded.

Results:
Between 2003 and 2012, a total of 50,737 patients underwent 88,108 stress tests, 501,239 diagnostic radiology exams, and 17,194 diagnostic coronary angiograms, with 177,957 patient years of follow-up. Mean age at first stress test was 60±14 years, 56% of the patients were men, and the total number of stress tests per patient was 1.8±1.4 (range 1-18). When patients undergoing a nuclear-based stress test (PET-Rb/SPECT) at any time were compared to those who never had a nuclear-based stress test, 0.8±0.6 vs 0.7±0.4 total stress tests/year were performed, respectively (p<.001), with a total radiation exposure (including stress tests, all radiology exams, and diagnostic coronary angiography) of 16.2±18.5 vs. 6.0±15.5 mSv/patient-year (p<.001), and an aggregate total radiation exposure from diagnostic angiography of 16 vs. 11%. For patients undergoing a nuclear-based stress test at any time, the total aggregate radiation exposure from nuclear stress testing was 37% (for both men and women). If a stress-first/stress-only protocol was adopted, which would decrease isotope exposure by 75% as a result of administering only a single dose of isotope, using an institutional normal test rate of 57% over the study period, the aggregate radiation exposure from radiation-based testing dropped to 25% for the group.

Conclusion:
Adoption of a stress-first/stress-only protocol for nuclear-based cardiac stress tests results in a significant reduction in unnecessary radiation exposure for patients undergoing cardiac stress testing.
Abstract 13009: The Significance of ATP Therapy Failure During Appropriate ICD-Delivered Therapy in Patients With Ventricular Tachycardia
Authors: Giedrimiene Dalia , Coleman Craig , Guertin Danette , Kluger Jeffrey
Published: July 2021

Prospective clinical trials have demonstrated that ICD-delivered therapy reduces mortality in patients at risk for sudden cardiac arrest due to ventricular tachycardia (VT). ICDs through anti-tachycardia pacing (ATP) modalities are able to terminate spontaneous VT. Although ATP is highly effective in terminating VT in ICD patients, 5 - 30% of these events ultimately need shocks. Unsuccessful ATP attempts, as well as shocks, prolong the duration of the episode and are associated with poor clinical outcomes.

Methods:
Our study focused on 1873 ICD-delivered therapies in pts who received ICD implants from 2008 to 2012 and completed one year follow up. Only patients who received ATP therapy for the first time for a ventricular tachycardia (VT) event were included. All therapy zones contained ATP therapy followed by shock therapy.

Results:
806 pts with ICD implants for primary or secondary prevention were analyzed. Study population consisted of 636 (78.9%) males and 170 (21.1%) females with average age of 72.8±29.8y (range: 29 - 98y). 622 (77.2%) of these patients had successful termination of VT with ICD-delivered ATP therapy. In 184 (22.8%) patients with unsuccessful ATP, appropriate ICD shocks were delivered.

Only 66.8% of patients with failed ATP had successful VT termination after 1st ICD shock. More than 33% of patients required 2 or more ICD-delivered shocks, of which 13% required four or more.

No gender based difference was found regarding success for VT termination after first, second or multiple ICD delivered shocks.

Conclusions:
1) ATP therapy is successful in the majority of patients.

2) After ATP failure only 66.8% of pts respond to first ICD shock. 33.2% require multiple ICD shocks that delay VT termination and may lead to worse clinical outcomes.

3) ATP failure for VT termination may identify patients who are at increased risk for failure to respond to ICD shocks. A careful observation and further clinical correlation is warranted in this group.
Abstract 13090: Autonomic Dysfunction Exacerbates New-Onset Heart Failure in Patients with Hypertension after the 2011 Great East Japan Earthquake
Authors: Yamada Shinya , Suzuki Hitoshi , Misaka Tomofumi , Mizukami Hiroyuki , Sugimoto Koichi , Saitoh Shu-ichi , Suzuki Fumio , Takeishi Yasuchika
Published: July 2021

Introduction:
We and others have reported that the occurrence of heart failure (HF) increased after the Great East Japan Earthquake on March 11, 2011, but the association of hypertension with HF remains unclear. In Minamisoma City, located approximately 20 km north of the Fukushima Daiichi Nuclear Power Plant, we hypothesized that autonomic dysfunction due to chronic stressful conditions may be associated with new-onset HF in patients with essential hypertension.

Methods:
We studied 110 outpatients (63 males, mean age 73 years) with essential hypertension in Minamisoma Municipal General Hospital. Holter monitoring was performed between July, 2011 and March, 2012 to evaluate standard deviation of all R-R intervals (SDNN) and standard deviation of the 5-min mean R-R intervals (SDANN). During the follow-up period (20.8 ± 4.5 months) under anti-hypertensive therapy, there were 7 hospitalizations due to new-onset HF and 1 sudden cardiac death. With the exception of sudden cardiac death, study subjects were divided into two groups based on whether new-onset HF occurred (n=7, HF) or not (n=102, no HF). We compared systolic and diastolic blood pressures, SDNN and SDANN between two groups.

Results:
Although there were no differences in systolic and diastolic blood pressures, SDNN and SDANN were significantly lower in HF than in no HF (SDNN: 92.5 ± 30.0 ms vs. 139.2 ± 44.9 ms; SDANN: 83.4 ± 27.8 ms vs. 127.6 ± 43.8 ms, P<0.01, respectively). Based on the receiver operating characteristic analyses for new-onset HF, cut-off values of SDNN and SDANN were defined as < 94.0 ms and < 77.5 ms, respectively. Kaplan-Meier analyses demonstrated that event-free rates from new-onset HF were lower in patients with low SDNN and in those with low SDANN (P<0.01, respectively) as shown in Figure.

Conclusions:
These results suggest that autonomic dysfunction plays an important role in new-onset HF after catastrophic disasters in patients with hypertension.
Abstract 13113: Dipeptidyl Peptidase 4 Inhibition Ameliorates Hypertensive Heart Failure via Suppression of Angiotensin-ii-mediated Cardiac Na+/h+ Exchanger1 Pathway
Authors: Kawase Haruya , Bando Yasuko K , Aoyama Morihiko , Monji Akio , Mitsui Toko , Murohara Toyoaki
Published: July 2021

Introduction:
Hypertension is primary cause of heart failure (HF). Several reports demonstrated the blood-pressure (BP)-lowering property of dipeptidyl peptidase 4 (DPP4) inhibitors.

Hypothesis:
We tested the effect of a new DPP4 inhibitor teneligliptin on BP and HF using preclinical models.

Methods:
Spontaneously hypertensive rats (SHR; 10 week-old male) and normotensive counterpart (WKY) were treated with TEN (10mg/kg/day) for 4 weeks. Hypertensive HF was evaluated in terms of BP, cardiac function, histological remodeling, and pulmonary congestion.

Results:
Cardiac catheterization revealed that TEN ameliorated hypertension of SHR-CON (Fig.1). The maximum dP/dt of SHR-CON was elevated (10452±539 for SHR-CON and 5739±599 for WKY-CON), which was reduced by TEN (8033±656 in SHR-TEN) without affecting heart rate. Diastolic indices (minimum dP/dt and tau) were ameliorated by TEN. SHR-CON exhibited increase in heart and body weight (BW) ratio, left ventricular (LV) wall thickness, cardiomyocyte hypertrophy and fibrosis, which were attenuated by TEN. Elevated lung weight and BW ratio and circulating BNP level of SHR-CON were ameliorated by TEN. Cardiac and circulating DPP4 activities of SHR-CON were elevated, which was suppressed by TEN. Vasorelaxant signaling (Akt/eNOS) of each aorta and heart remained unaffected by TEN. Circulating angiotensin-2 (AT-II) was elevated in SHR-CON, which was suppressed by TEN without affecting ACE activity (Fig1). Because DPP4 interacts with Na+/H+ exchanger (NHE)-1 and -3, and NHE1 is related to hypertension and cardiac hypertrophy. In SHR-CON heart, NHE1 expression was elevated (Fig1), which was decreased by TEN. NHE-1 of cultured cardiomyocytes was upregulated by AT-II.

Conclusions:
TEN ameliorates hypertensive HF via normalizing elevated AT-II through an ACE-independent pathway, leading to reversal of hypertensive cardiac remodeling modulated by pathological AT-II/NHE-1 axis.
Abstract 13121: Different Presentation Mode of Acute Myocardial Infarction is Associated With Antecedent Therapy With Nitrates and β-blockers
Authors: Kojima Sunao , Ogawa Hisao ,   The Japanese Acute Coronary Syndrome Study (JACSS)Group
Published: July 2021

Introduction:
Brief episodes of ischemia increases cardiac tolerance to a subsequent major ischemic insult. Prehospital medication may affect the mode of presentation in acute myocardial infarction (AMI) and pharmacologically precondition the heart toward ischemic episodes.

Hypothesis:
We assessed the hypothesis that antecedent therapy confers cardioprotection in patients suffering an AMI.

Methods:
The Japanese Acute Coronary Syndrome Study (JACSS) is a retrospective and multicenter observational study that is being conducted at 35 medical institutions in Japan. The JACSS database includes information on consecutive 1,204 patients who were hospitalized within 48 hours after the onset of AMI.

Results:
A total of 1,010 ST-elevation myocardial infarction (STEMI) and 194 non STEMI (NSTEMI) patients were included and the differences of the mode of presentation, prehospital medication and coronary risk factors were investigated in the present study. Coronary risk factors such as sex, hypertension, diabetes mellitus, hypercholesterolemia, smoking, obesity and previous coronary artery disease were comparable between STEMI and NSTEMI groups. Prehospital medication with aspirin, nitrates, β-blockers and calcium-channel blockers but not with angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and statins were associated with the onset as NSTEMI. A stepwise regression analysis including coronary risk factors and prehospital medication revealed that chronic therapy with nitrates and β-blockers reduced the onset as STEMI compared with that as NSTEMI (table)

Conclusions:
Antecedent therapy with nitrates and β-blockers was associated with reduced severity of myocardial injury in response to an acute coronary event. Our findings may help to explain the missing link between a shift away from STEMI in favor of NSTEMI and a combined capability of nitrates and β-blockers to act as pharmacological inducers of ischemic preconditioning.
Abstract 13181: Characteristics of Diurnal Change of Pulse Rate in Resistant Hypertension
Authors: Watanabe Hiroaki , Kabutoya Tomoyuki , Hoshide Satoshi , Eguchi Kazuo , Kario Kazuomi
Published: July 2021

Introduction:
Sympathetic hyperactivity is one of the most important causes of resistant hypertension. Ambulatory blood pressure monitoring (ABPM) allows measurement of blood pressure (BP) and pulse rate (PR) throughout the day, as well as measurement of diurnal variations in BP and PR, which are controlled by the autonomic nervous system.

Hypothesis:
We hypothesized that abnormal diurnal change of BP and PR are associated with resistant hypertension.

Methods:
We evaluated 1003 patients with hypertension who were enrolled in the Japan Morning Surge Home Blood Pressure Study and were using ABPM. Resistant hypertension was defined as clinic BP≧140/90 mmHg despite the use of optimal doses of 3 classes of antihypertensive drugs, including a diuretic. BP or PR dipper status was defined as (awake systolic BP (SBP) or PR-sleep SBP or PR)/awake SBP or PR ≧0.1. BP or PR nondipper status was defined as (awake SBP or PR-sleep SBP or PR)/awake SBP or PR <0.1 and ≧0. BP and PR riser status were defined as awake SBP or PR < sleep SBP or PR.

Results:
The numbers of PR nondippers and PR risers in the resistant hypertensive groups were significantly greater than those in the non-resistant hypertensive groups (x2=9.35, p=0.009), but there were no significant differences in the diurnal variation of BP between the resistant hypertensive and non-resistant hypertensive groups (x2=3.10, p=0.21). In the resistant hypertensive groups, the proportion of PR risers was approximately three-fold greater than that in the non-resistant hypertensive groups after adjustment for age, gender, 24-h BP, PR, and BP variation (Hazard ratio 2.94, 95%Cl 1.25-6.91, p=0.013), but there were no significant differences in the proportion of PR nondippers (Hazard ratio 1.36, 95%Cl 0.82-2.26, p=0.23).

Conclusions:
A riser pattern of PR was associated with resistant hypertension. ABPM may be useful to identify resistant hypertensive patients who have autonomic nervous system dysfunction.
Abstract 13190: Integrin Linked Kinase is Required for Integrity of Cardiac Ion Current and Electrophysiologic Function
Authors: Qi Xiao- Y , Tadevosyan Artak , Le Quang Khai , Naud Patrice , Shi Yan- F , Chartier Denis , Maguy Ange , Tardif Jean- C , Dobrev Dobromir , Nattel Stanley
Published: July 2021

Introduction:
The cardiac adaptor protein integrin-linked kinase (ILK) is a regulator of cardiac structure/function. This study investigated the ventricular cardiomyocyte ion channel/electrophysiological remodeling caused by cardiomyocyte-directed ILK deletion (ILK-KO) in mice.

Methods:
Mice expressing the mckCRE transgene and 2 loxP1-flanked ILK-alleles (ILK-KO) were compared to littermate controls (WT). Perforated and tight-seal patch clamp were used respectively to record action potentials (APs) and ion currents in isolate ventricular cardiomyocytes. Cardiac function was assessed by echocardiography and rhythms were recorded by 24 hr telemetry in conscious mice.

Results:
ILK-KO mice died suddenly (50% mortality at 8 wks and 100% mortality at 18 wks) with progressive dilated cardiomyopathy. Spontaneous ventricular tachyarrhythmias (VTs) were recorded in 60% (*P<0.001 vs WT) at 10 wks. At 5 wks, prior to cardiac dysfunction, ILK-KO increased action potential duration (APD) by 68%*. I
CaL
and I
K1
were unchanged, but fast inactivating transient outward (I
to,f
) and slowly inactivating delayed rectifier (I
K,slow
)

K

currents were reduced by 40%* and 34%* respectively. At 10 wks, LV systolic, diastolic dimensions increased by 72%*, 31%* respectively and LVEF decreased by 42%*; I
CaL
, I
K1
, I
to,f
and I
K,slow
were all significantly decreased (by 23%, 32%, 38%, 53% respectively). APD was increased by 114%* and EADs/triggered activity were recorded. To assess mechanisms of specific K
+
current interactions, ILK was immunoprecitated (IPed) from cardiomyocyte membranes and K
+
channel subunits detected by immunoblot (Figure). Kv4.2 co-IPed with ILK, indicating direct physical interaction; whereas Kv1.4, Kv4.3 and KChIP2 did not.

Conclusions:
Cardiomyocyte ILK-deletion causes dilated cardiomyopathy, extensive ionic remodeling, VT and sudden death. Early K
+
current changes and co-IP point to a specific interaction with Kv4.2 subunits in pathogenesis.
Abstract 13200: Acute Inhibition of Phosphodiesterase Type 5A (PDE5) with Sildenafil Augments Contractility of LV and Myocyte in Heart Failure
Authors: Li Tiankai , Cheng Heng-Jie , Zhang Xiaowei , Li Wei-Min , Cheng Che Ping
Published: July 2021

Background:
Sildenafil (SIL), a selective inhibitor of cGMP-specific PDE5 has been shown to exert profound cardioprotection in various cardiac pathologies. This beneficial action has been attributed to its selective vasodilatation effect. However, recent studies indicate that SIL may augment cGMP signaling and produce direct cardiac inotropic modulation, thus affords its cardioprotection in heart failure (HF). Whether SIL plays a role in cardiac contractile behavior in HF remains undetermined. SIL has been reported variably to have a positive, negative or no inotropic effect on cardiac contractility in HF. These disparate observations may be due to the confounding effects of loading conditions and dosage of SIL. We tested the hypothesis that SIL evokes positive modulation on cardiac contractility which importantly contributes to its beneficial action in HF.

Methods:
We measured Left ventricular (LV) contractility changes after SIL (0.4 mg/kg, iv), and compared myocyte contractile and [Ca
2+
]
i
transient ([Ca
2+
]
iT
) responses to SIL (10
-6
M) in 8 rats with isoproterenol (ISO)-induced HF (3 months after 170 mg/kg sq for 2 days). LV contractility was measured by pressure-volume analysis.

Results:
Compared with normal controls, ISO-treated rats had established HF after ISO at 3 months with significantly elevated plasma norepinephrine, LV dilatation, and decreased ejection fraction (EF, 29% vs 61%). Compared with baseline, acute administration of SIL caused no change in LV systolic blood pressure and heart rate, but increased EF (43% vs 29 %). LV time constant of relaxation (t) (12.2 vs 15.1 ms) decreased. The slopes of LV pressure-volume relations of E
ES
(49%, 0.92 vs 0.61 mmHg/μl) and M
SW
(42%, 97.4 vs 68.6 mmHg) were increased, indicating significantly enhanced LV contractility. These responses were accompanied with about 24% increases in cell contraction (dL/dt
max
, 97.1 vs 78.3 μm/s) and relaxation (dR/dt
max
, 63.7 vs 51.5 μm/s) and relatively unchanged [Ca
2+
]
iT
(0.149 vs 0.137), while myocyte Ca
2+
sensitivity was enhanced.

Conclusions:
In HF, positive inotropic effect is induced by acute inhibiting PDE5 with clinically-relevant concentrations of SIL. The cardiostimulatory and vasodilatory actions of SIL make it suitable for the treatment of HF.
Abstract 13230: Attenuation of Clock-bmal1 Transcriptionally Decreases the Expression of β1-ar to Anticipate the Occurrence of Ventricular Arrhythmia After Chronic Heart Failure
Authors: Yuan Jiamin , Zou Jiangang
Published: July 2021

Circadian rhythms influence the incidence of sudden cardiac death after chronic heart failure (CHF) but the underlying mechanisms are not well defined. We sought to investigate the role of the β-adrenergic receptor (β-AR) in cardiac circadian disorders and ventricular arrhythmia(VA) after CHF.

CHF guinea pigs was created by transverse aorta constriction. Circadian variations of the myocardial expressions ofβ1-AR, β2-AR and circadian genes CLOCK and BMAL1 were examined by real time reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Sham operated animals showed circadian oscillations in the expression ofβ1-AR and CLOCK-BMAL1(P<0.05). However, the expression ofβ1-AR and CLOCK-BMAL1 were attenuated in guinea pigs with CHF(P<0.05). Then, electrocardiograms of Langendorff-perfused hearts with isoprenaline(β-AR nonselective agonist ,ISO), ISO + CGP-20712A(β1-AR selective antagonist, CGP) and ISO + ICI118551(β2-AR selective antagonist, ICI) at CT3 and CT15 were recorded and ventricular arrhythmias were induced by programmed electrical stimulation (PES). During ISO and ISO + ICI infusion, the diurnal variation in response of β-AR activation translated to a greater incidence of VA in CT15(P<0.05). Next, infections of Ad-CLOCK and/or Ad-BMAL1 were applied to overexpress CLOCK, BMAL1 and CLOCK-BMAL1 in the guinea pig ventricular cardiomyocytes. Ad-CLOCK and Ad-BMAL1 co-infection resulted in overexpression of β1-AR and a greater incidence of arrhythmic activity in myocytes. At last, chromatin immunoprecipitation assay(ChIP) and luciferase(LUC) were applied to determine whether CLOCK-BMAL1 transcriptionally regulateβ1-AR expression. ChIP-qPCR analysis and luciferase revealed that BMAL1 could bind to enhancer of β1-AR to regulate arrhythmia severity after CHF(P<0.05).

We conclude that circadian rhythms of myocardial β1-AR and CLOCK-BMAL1 activities are disturbed after CHF. Attenuation of CLOCK-BMAL1 transcriptionally decreases the expression of β1-AR to anticipate the occurrence of ventricular arrhythmias after CHF.
Abstract 13262: A Potent and Selective Covalent Inhibitor of JNK Protects Heart from both Ischemia/Reperfusion- and Hypertension-induced Heart Failure
Authors: Wang Jinli , Sun Wanqing , Ma Yina , Techiryan George , Zhang Tinghu , Zhang Jianming , Li Ji
Published: July 2021

Introduction:
c-Jun NH
2
-terminal kinases (JNKs) are critical mediators of a variety of detrimental stimuli including ischemia-reperfusion (I/R) and mechanical stress induced by pressure overload. Recently, we reported that a novel synthesized highly selective JNK inhibitor, JNK-IN-8, can form an ATP site-directed covalent bond with a conserved cysteine residual in all JNKs. Therefore, JNK-IN-8 may be broadly useful as a pharmacological tool for inhibiting JNK-dependent signal transduction that is involved in various pathological conditions.

Hypothesis:
The potent JNK inhibitor, JNK-IN-8, could act as a cardioprotectant against ischemia/reperfusion (I/R)- or hypertension-induced heart failure.

Methods:
The effects of JNK-IN-8 were monitored in a mouse I/R models with the left anterior descending coronary artery (LAD) occluded and subsequently released, and a mouse model of trans-aortic constriction (TAC), in which pressure overload hypertrophy was induced in 2 weeks.

Results:
JNK-IN-8 significantly reduced myocardial infarct area by 40% in I/R model relative to the vehicle group (p<0.01). Interestingly, the immunohistochemistry data showed that JNK-IN-8 treatment attenuated macrophage infiltration and caspase-3 executed apoptosis in TAC mice (p<0.01 vs. vehicle group). Moreover, the staining of wheat germ agglutinin (WGA) and Masson trichrome revealed a decrease in hypertrophy and fibrosis in the TAC hearts of JNK-IN-8 treated group (p<0.05 vs. vehicle group). The immunoblotting data demonstrated that JNK-IN-8 selectively attenuated both I/R- and pressure overload-induced cardiac JNK and downstream p-p66
shc
signaling pathways, while the levels of other family signals (p-p38 and p-ERK) remained unchanged, further indicating the specificity of JNK-IN-8 on JNK signaling in the heart.

Conclusions:
JNK-IN-8 can reduce I/R-injury induced myocardial infarction size, and attenuate pressure overload induced inflammation, apoptosis, hypertrophy and fibrosis. Thus JNK-IN-8 is a potential therapeutic drug for both I/R injury and pressure overload induced hypertrophy.
Abstract 13275: The Intermountain Risk Score is a Robust Predictor of Mortality in Patients With Chronic Kidney Disease
Authors: Rassa Allen C , Horne Benjamin D , McCubrey Raymond , Bair Tami L , Muhlestein Joseph B , Morris Donald , Anderson Jeffrey L
Published: July 2021

Introduction:
Chronic kidney disease (CKD) is a common disorder associated with increased cardiovascular mortality. The Intermountain Risk Score (IMRS) is an electronic risk calculator that utilizes the complete blood count (CBC), basic metabolic panel (BMP), age and sex to predict all-cause mortality. We tested whether IMRS predicts mortality in CKD patients (pts) and is additive to CKD staging. We also tested whether serum phosphate (PO4) or urinary albumin (U-alb)/creatinine (Cr) ratio adds predictive value.

Methods:
From October 2005 to May 2013, pts with CKD classes IIIa-V seen in the Intermountain Healthcare system with concurrent BMP and CBC tests were followed for survival at 1y (N=3,872) and 5y (N=3,727). Survival analyses were performed for pre-defined IMRS low-, medium- and high-risk groups for combined and separate CKD stages, and for PO4 and U-alb/Cr. Receiver operator characteristic curves were used to generate c-statistics.

Results:
For pts across the spectrum of CKD, mortality was significantly increased with medium- and high-risk compared to low-risk IMRS categories (1y medium-risk hazard ratio [HR]=4.60 [95% CI: 2.97, 7.12], 1y high-risk: HR=17.6, [11.46, 27.14]; and 5y medium-risk HR=2.5 [1.9, 3.2], 5y high-risk: HR=6.87 [5.44, 8.68], P < 0.001 for all). When adjusted for CKD stage, IMRS remained predictive (1y: HR=3.85 [2.47, 5.99] for medium-risk, HR=12.66 [8.11, 19.76] for high-risk; and 5y: HR=2.30 [1.80, 2.95] for medium-risk, HR=5.55 [4.36, 7.06] for high-risk, P < 0.001 for all). IMRS predicted 1y mortality more efficiently (c=0.735 [se 0.013]) than CKD stage (c=0.660 [se 0.013]); while combining IMRS and CKD stage increased the c-statistic to c=0.759 (se 0.014). PO4 predicted mortality (HR=1.23 [1.15-1.31]) but added only slightly to the IMRS 1y predictive ability (c=0.741 [se 0.016]). U-alb/Cr was not independently associated with mortality (HR=1.01 [0.99-1.01]).

Conclusion:
IMRS is a strong predictor of mortality in patients with CKD and is robustly complementary to CKD stage in refining risk stratification. Given the universal electronic availability and low cost of CBC and BMP, IMRS may represent a major advance in CKD risk assessment and management.
Abstract 13286: Non-Specific Intraventricular Conduction Delay and Risk of Sudden Death
Authors: Uy-Evanado Audrey , Teodorescu Carmen , Reinier Kyndaron , Narayanan Kumar , Chugh Harpriya , Gunson Karen , Jui Jonathan , Chugh Sumeet S
Published: July 2021

Introduction:
We and others have reported an independent association between prolonged QRS duration and risk of sudden cardiac death (SCD) in the general population. Left and right bundle branch block have been studied previously, but there is little information regarding non-specific intraventricular conduction delay and risk of SCD.

Hypothesis:
Completed conduction defects, including non-specific IVCD, are associated with increased SCD risk.

Methods:
Sudden cardiac death cases and controls from an ongoing large population based study in the Northwestern US (2002 to 2010) were included if age ≥ 35 years with a non-paced 12-lead ECG (recorded prior and unrelated to SCD in cases). QRS morphology was subcategorized as normal, intermediate [left anterior fascicular block (LAFB), left posterior fascicular block (LPFB), and incomplete right or left bundle branch block (IRBBB/ILBBB)] or completed conduction defects [left bundle branch block (LBBB), right bundle branch block (RBBB), or nonspecific intraventricular conduction delay (IVCD)]. Comparisons were conducted using chi-square tests for categorical variables and independent samples t-tests for continuous variables. Logistic regression was used to evaluate the association of QRS morphology with SCD.

Results:
We evaluated 761 SCD cases (64% male) and 539 controls (65% male). Cases were significantly older (69.7 vs 66.3 years, p<0.0001) with greater QRS duration (102 vs. 98 ms, p=0.001). For conduction categories, intermediate or completed conduction defects were significantly more common in cases whereas normal QRS morphology was more common among controls (p=0.01). And for specific morphology overall, QRS morphology patterns differed between cases and controls (p=0.03); abnormal QRS morphologies were more frequent in cases than controls except for LAFB. After adjustment for age and gender, however, only a finding of LBBB or non-specific IVCD remained a significant predictor of SCD [OR 1.34 (95% CI 1.03-1.75)].

Conclusions:
LBBB and non-specific IVCD, but not RBBB, are significant predictors of SCD in the general population. These findings contribute to the utility of the 12-lead EKG for SCD risk stratification.
Abstract 13291: Left Ventricular Assist Device Support is Associated with Sustained Cardiac CamKII Activation and Increased MEF2
Authors: Castillero Estibaliz , Ji Ruiping , Zhang Xiaokan , Choi Vivian , Mannan Ayesha , Najjar Marc , Yerebakan Halit , Sorabella Robert , Wang Catherine , Naka Yoshifumi , Mancini Donna M , Sweeney H L , Schulze Paul C , Ali Ziad , George Isaac
Published: July 2021

Background:
Ca2+/calmodulin-dependent protein kinase (CaMK)II has been implicated in impaired myocardial Ca2+ signaling and may play an important role in the development of heart failure (HF). The objective of this study was to characterize CAMKII signaling in patients with HF before and after prolonged left ventricular assist device (LVAD) support.

Methods:
LV apex tissue pairs were collected in patients with dilated cardiomyopathy (n=10) at LVAD implantation and explantation. Normal cardiac tissue was used as control (n=4). Total protein, as well as cytoplasmic and nuclear fractions, were analyzed by Western Blot analysis.

Results:
The duration of LVAD support ranged from 48 to 595 days (mean = 271±54) with no patient exhibiting myocardial recovery. Total CamKIIδ levels in failing hearts were significantly higher than normal hearts and increased after LVAD, mainly due to an increase in cytoplasmic CaMKIIδC, which regulates Ca2+ handling (Table 1). Nuclear CaMKIIδB, which regulates Ca2+ gene transcription, did not change. Calmodulin remained increased in the nuclear and cytoplasmic fractions after LVAD. CaMKII autonomous, non-CaM-dependent activity, reflected by phosphorylation in Thr207, was increased pre- and post LVAD in cytoplasmic CaMKIIδC. The CaMKII-dependent myocyte enhancer factor 2 (MEF2) was increased pre- and significantly further post LVAD in the nucleus while decreased in the cytoplasm, suggesting translocation into the nucleus after LVAD support. Class IIa HDACs 4 and 5 interact with MEF2, resulting in repression of MEF2-dependent genes. Phosphorylated levels of HDAC4 and HDAC5 were increased pre- and post LVAD, which would result in activated MEF2.

Conclusions:
This study shows for the first time an increase of the hypertrophic factor MEF2 associated with persistent activation of CamKIIδC after prolonged LVAD support, which may have implications for cardiac remodeling during mechanical support.
Abstract 13313: First Report of the New Point-of-Care TEG: a Multicenter Validation Study of the CORA® System
Authors: Gurbel Paul A , Bliden Kevin P , Monroe Amy L , Slusser Wendi L , Gesheff Martin , Franzese Christopher , Muresan Adina A , Brunner Norman E , Carlos G. , Delmenico Peter R , Cohen Eli , Raviv Gabriel , Haugen DeAnna L , Tantry Udaya S , Ereth Mark H
Published: July 2021

Background:
Thrombelastography (TEG) is an established but labor intensive method for assessing global hemostasis for the management of bleeding and thrombotic risk in surgical, cardiovascular, and trauma patients. We performed the initial validation study of the first true point-of-care TEG, the CORA® (COagulation Resonance Analyzer or TEG-6S system). CORA uses resonance-frequency viscoelasticity measurements and a disposable multi-channel microfluidic cartridge to assess hemostasis and response to antiplatelet therapy.

Methods:
TEG assays (n=5,100) were performed from the blood of healthy volunteers (n=160) and patients undergoing coronary revascularization (n=300) collected at

3 hospitals. Quality controls were also assayed. The performance of the TEG-6S system was compared with the conventional TEG 5000 system in accordance with Clinical Laboratory Standards Institute Guidelines.

Results:
Regression analysis demonstrated a strong correlation (R) between the two systems by all standard measures and a lower coefficient of variation (CV %) with the CORA system at all hospitals (Table). Receiver operating characteristic (ROC) curve analysis showed an excellent correlation between platelet mapping methods (AUC≥0.90, p<0.001) and there was a substantial agreement for measuring antiplatelet response to aspirin (k=0.67, agreement=87%) and P2Y12 inhibitors (k=0.69, agreement=86%).

Conclusion:
The new point-of-care TEG-6S system is associated with improved precision, greater ease of use, and a strong correlation as compared to the conventional TEG 5000 system. The TEG-6S will facilitate future trials of personalized antiplatelet therapy and improve the assessment of bleeding and thrombotic risk in cardiovascular, surgical, and trauma patients.
Abstract 13345: Efficacy and Safety of an Anticoagulation Clinic in Low-income Brazilian Patients With Heart Disease: a Randomized Clinical Trial
Authors: Martins Maria A , Oliveira João A , Ribeiro Daniel D , César Cibele C , Nobre Vandack A , Palhares Daniel M , Rocha Manoel O , Ribeiro Antonio L
Published: July 2021

Introduction:
Anticoagulation clinics (AC) have better impact on anticoagulation control than usual medical care (UMC). However, there is no randomized trial testing the results of AC in low-income realities. We sought to examine the performance of an AC in a group of patients treated at a Brazilian public hospital.

Hypothesis:
The assistance provided by AC presents difference in TTR when compared to the UMC.

Methods:
This was a randomized clinical trial to test the efficacy and safety of a recently-implemented AC over UMC in a group of outpatients with heart disease. The primary and secondary endpoints were time in the therapeutic range (TTR) and warfarin-associated complications, respectively. Overall, 280 patients were enrolled and randomly assigned to one of the two arms: group A: one year at AC (A1: first semester; A2: second semester); and group B: one semester receiving UMC (B1) and other at AC (B2).

Results:
The mean age was 56.8±13.1 years and patients were mostly female (54.6%). The median monthly income was 464 US dollars. Low literacy was predominant in this group of studied patients (>68%). A1 showed higher TTR (62.4±20.8%) than B1 (55.1±28.5%) (p=0.014). An improvement of TTR was observed within group B, rising from 55.1±28.5% (B1) to 62.2±23.1% (B2) (p=0.008). A1 showed lower incidence rate (IR) per patients-year (p-y) of total bleedings than B1 (incidence rate ratio (IRR): 0.78; p=0.041) and a decline in the IR p-y was found for intra-group comparisons, both presenting IRR 0.58; p<0.001. A1 showed lower IR p-y for thromboembolism than B1 (IRR=0.12; p=0.047). (Clinical trial registration: www.clinicaltrials.gov/. Identifier: NCT01006486)

Conclusions:
AC helped increase TTR and reduce warfarin-complications, even in low-income settings. Extending this assistance to similar populations in other Latin American countries could reduce hospitalizations and deaths related to warfarin use.
Abstract 13377: Predictors of High Operator Radiation Exposure During Cardiac Catheterization: Insights From the Radicure (Radiation Reduction During Cardiac Catheterization Using Real-time Monitoring) Study
Authors: Christopoulos Georgios , Papayannis Aristotelis C , Alomar Mohammed , Kotsia Anna P , Michael Tesfaldet T , Rangan Bavana V , Roesle Michele , Shorrock Deborah , Makke Lorenza , Maragkoudakis Spyros , Mohammad Atif , Sarode Karan , Chambers Charles E , Banerjee Subhash , Brilakis Emmanouil S
Published: July 2021

Background:
The RadiCure study examined the impact of real-time radiation monitoring on patient and operator exposure during cardiac catheterization. We sought to identify the factors associated with increased radiation exposure of the first operator.

Methods:
We studied the baseline clinical characteristics and procedural outcomes of 505 patients that were enrolled in the RadiCure study from January 2012 to May 2014. Multivariable analysis of high (above median or >1.0 mrem) exposure of the first operator was performed. Variables with a significant (p<0.10) association on univariable analysis were included in the multivariable model.

Results:
Mean age was 65±8 years and most patients were men (99%) with a high prevalence of diabetes mellitus (54%), and prior coronary artery bypass graft surgery (30%). Median procedure time was 27 (14-51) minutes; radial access was used in 18% of cases and chronic total occlusion (CTO) interventions constituted 7% of the procedures. Median fluoroscopy time was 6.2 (2.5-12.5) minutes; median patient Air Kerma (AK) radiation exposure was 0.908 (0.602-1.636) Gray; and median first operator exposure was 1.0 (0.5-2.2) mrem. On multivariable analysis, radial access (Odds ratio [OR] 6.62, 95% Confidence Interval [CI] 3.13-14.76), followed by CTO intervention (OR 5.53, 95% CI 1.73-20.71) and patient AK radiation exposure > 0.9 Gray (OR 4.56, 95% CI 2.32-9.19) were found to be the strongest independent predictors of high first operator exposure. Real-time radiation exposure monitoring and use of a radioabsorbent drape were shown to have a significant protective effect (OR 0.33, 95% CI 0.19-0.57; and OR 0.38, 95% CI 0.18-0.77; respectively) (Figure 1).

Conclusions:
In the RadiCure study, high patient AK exposure, radial access and CTO intervention were associated with high first operator exposure. Real-time radiation monitoring and use of a radioabsorbent drape were independently associated with lower operator radiation exposure.
Abstract 13397: Determining the Optimal Cutpoint Value for the Diagnosis of Hypertriglyceridemia in the Nonfasting Population
Authors: White Khendi T , Moorthy M.V. , Akinkuolie Akintunde O , Demler Olga , Ridker Paul M , Cook Nancy R , Mora Samia
Published: July 2021

Background:
Nonfasting triglycerides may be superior to fasting triglycerides at predicting CVD. However, guideline cutpoints are based on fasting triglycerides. We aimed to determine the optimal clinical cutpoint for nonfasting triglycerides.

Methods:
Among 26,509 apparently healthy women, nonfasting blood samples (<8 hours since last meal) were obtained from 6,391 participants who were prospectively followed for up to 17 years for incident CVD (MI, ischemic stroke, CABG/PTCA, CVD death). The optimal diagnostic threshold for nonfasting triglycerides was determined by univariate logistic regression model using c-statistics for triglycerides between 100-300 mg/dL, with 10-fold cross-validation and bootstrapping in multivariable models. In addition, we tested the proposed nonfasting cutpoints of 175 mg/dL (European Atherosclerosis Society), 180 mg/dL (Athens Expert Panel), and 200 mg/dL (AHA).

Results:
The optimal threshold was identified as 175 mg/dL (Table). Performance of this optimal threshold was evaluated using 10-fold cross validation and bootstrapping in multivariable models that included age, smoking, blood pressure, hormone use, menopausal status, lipids, diabetes, BMI, and CRP. The adjusted hazard ratio (HR) for nonfasting triglycerides ≥ vs <175 mg/dL predicting incident CVD events was 1.69 (95% CI, 1.34-2.13, p<0.001). Adjusted HRs for triglycerides ≥ vs <175 mg/dL measured 0-4 and 4-8 hours since last meal were 1.73 (1.27-2.36, p<0.001) and 1.63 (1.15-2.32, p=0.006), respectively.

Conclusion:
This is the first study to identify a diagnostic threshold for nonfasting hypertriglyceridemia, finding an optimal cutpoint of 175 mg/dL. Of note, the currently recommended AHA cutpoint for nonfasting triglycerides of 200 mg/dL had substantially lower sensitivity and could under-diagnose hypertriglyceridemia among nonfasting individuals.
Abstract 13423: Pharmacologic Inhibition of the NLRP3 Inflammasome Improves Left Ventricular Dysfunction after Severe Ischemic and Non-Ischemic Injury
Authors: Marchetti Carlo , Toldo Stefano , Chojnacki Jeremy , Mezzaroma Eleonora , Carbone Salvatore , Nordio Andrea , Sonnino Chiara , Federici Massimo , Van Tassell Benjamin , Zhang Shijun , Abbate Antonio
Published: July 2021

Introduction:
The formation of the NLRP3 inflammasome during injury to the heart amplifies the inflammatory response and mediates further damage. An inhibitor of the NLRP3 inflammasome was shown to reduce ischemia/reperfusion injury in the mouse.

Hypothesis:
We hypothesize that the NLRP3 inflammasome inhibitor would limit left ventricular (LV) dysfunction following severe ischemic (non-reperfused myocardial infarction [MI]) and non-ischemic (doxorubicin-induced) injury to heart.

Methods:
Adult male CD-1 male mice underwent permanent ligation of the left anterior descending coronary artery to induce a large non-reperfused MI (ischemic model) or injection of doxorubicin 10mg/kg to induce LV systolic dysfunction (non-ischemic model). The NLRP3 inflammasome inhibitor (16673-34-0, 100 mg/kg) or vehicle (N=6-8 per each group) were administered intraperitoneally daily for 7 days. Transthoracic echocardiography was performed to measure LV end-diastolic diameter (EDD) and LV fractional shortening (FS). We used Masson’s Trichrome stain to measure infarct size (ischemic model) or interstitial fibrosis (non-ischemic model).

Results:
Permanent coronary ligation led to a large non-reperfused MI and a significant increase in LVEDD and a reduction in LVFS (ischemic model). When compared with vehicle, treatment with the NLRP3 inflammasome inhibitor significantly limited LV enlargement (4.53±0.14 vs vehicle 4.95±0.04mm, P=0.006) and limited systolic dysfunction after AMI (Figure). A significant increase in interstitial fibrosis and reduction in LVFS was seen after doxorubicin treatment (non-ischemic model), and treatment with the inhibitor significantly reduced interstitial fibrosis (0.73%±0.14 vs vehicle 3.35%±0.83, P=0.001) and preserved LVFS (Figure).

Conclusion:
Inhibition of the NLRP3 inflammasome using a small molecule, 16673-34-0, reduces cardiac injury and limits LV systolic dysfunction following ischemic and non-ischemic injury.