bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11621: Fibrillin-1 Gene Mutations in Left Ventricular Non-Compaction Cardiomyopathy
Authors: Parent John J , Towbin Jeffrey A , Jefferies John L
Published: July 2021

Introduction:
Left ventricular non-compaction cardiomyopathy (LVNC) is a rare and unique cardiomyopathy. Its presentation can range from a benign phenotype to overt heart failure and sudden cardiac death. The genetics of LVNC are not completely understood and current genetic testing has a yield of about 30% in identifying a causative gene mutation. We present a series of patients with LVNC and fibrillin-1 (FBN1) gene mutations.

Hypothesis:
We hypothesize that FBN1 gene mutations can lead to LVNC by way of its role in the myocardial extracellular matrix during cardiac development.

Methods:
A retrospective review of all patients with LVNC at our institution was performed for purposes of another investigation. The process unexpectedly identified patients with LVNC and FBN1 gene mutations, as well as LVNC and Marfan syndrome.

Results:
Approximately 150 patients are followed in our clinic with LVNC. We screened this population and found 51 patients on medical therapy for reduced function. We retrospectively reviewed gene testing in these 51 patients, when available, and identified 5 patients (10%) with an FBN1 gene mutation. All 5 patients had a dilated LVNC phenotype and previous or current evidence of left ventricular dysfunction. Syndrome breakdown as follows: 3 with Marfan, 1 with Shprintzen-Goldberg, and 1 with no identifiable syndrome. Dilated cardiomyopathy/LVNC gene testing was performed in 3 patients; 2 had disease causing myosin heavy chain 7 gene defects and 1 had no defects.

Conclusions:
The role of FBN1 in the human myocardium is not completely understood but it is expressed in the developing fetal heart and is a component of the myocardial extracellular matrix. Although causation has not been proven by our report, it certainly raises interest in a mechanistic relationship between LVNC and FBN1 given the increased prevalence of Marfan syndrome and probable increased prevalence of FBN1 gene mutations in this cohort of LVNC patients in light of FBN1.
Abstract 11670: Presence of Dissociated Pulmonary Vein Activity After Isolation Depends on Fibrillatory Excitation in Pulmonary Vein
Authors: Kaneshiro Takashi , Suzuki Hitoshi , Matsumoto Yoshiyuki , Nodera Minoru , Kamiyama Yoshiyuki , Takeishi Yasuchika
Published: July 2021

Background:
Circumferential pulmonary vein (PV) isolation has been widely accepted as catheter ablation for atrial fibrillation (AF). Dissociated PV activity (DPVA) may appear after PV isolation, however, the electrophysiological property and clinical implication of DPVA have not been revealed.

Methods and Results:
The study subjects were consecutive 37 patients (62±8 years, 28 men) with drug-refractory AF who underwent successful PV isolation. Electrophysiological property of left atrium (LA) and PV during and after PV isolation were investigated.

Excluded 21 PVs without LA-PV connection before procedure, all of 112 PVs with successful isolation were analyzed. DPVA appeared in 14 PVs (13%) after PV isolation, from left superior PV in 7 (50%), right superior PV in 5 (36%) and left inferior PV in 2 (14%). Mean cycle length (CL) of DPVA was 5180±3080 ms. DPVA appeared in 9 of 37 PVs (24%) without existence of AF, but in 5 of 75 PVs (7%) with existence of AF during procedure (P=0.008). There was the tendency that the CL of DPVA was shorter with existence of AF compared to that without existence of AF (3792±1815 vs. 6682±3041 ms, P=0.08), and the suppression of DPVA was observed by over drive pacing inside of PV with PV capture in several cases. There was not significant relationship between the presence of DPVA and AF recurrence with 2-month blanking period after PV isolation.

Conclusions:
The presence of DPVA after PV isolation depended on the existence of AF during procedure, but was not significantly related to the AF recurrence after PV isolation. The long CL and suppressive maneuver with PV over drive pacing suggested the vulnerability of DPVA. Thus, these findings suggest that passive and/or spontaneous fibrillatory excitation in PV might suppress the automatic activity of myocardial sleeves in PV.
Abstract 11711: Valproic Acid, a Class [[Unable to Display Character: І]] Histone Deacetylase Inhibitor, Suppresses the Development of Severe Pulmonary Hypertension in Rats
Authors: Lan Beidi , Hayama Emiko , Nakanishi Toshio
Published: July 2021

Introduction:
Pulmonary hypertension (PH) is a progressive vascular remodeling disease characterized by exuberant cell proliferation, apoptosis resistance, and inflammation that contributes to increased pulmonary arterial resistance. Histone deacetylases (HDACs) and histone acetyltransferases shift acetyl groups from histone and non-histone proteins and enhance gene transcription by post-translational modifications. Valproic acid, a class I HDAC inhibitor, is a widely used antiepileptic drug with low toxicity and also shows supportive efficacy in cancer treatment by inhibiting cancer cell proliferation and inflammation.

Hypothesis:
We assessed the hypothesis that HDAC inhibition may attenuate excessive cell proliferation and inflammation and improve vascular remodeling in a severe PH rat model.

Methods:
To compare the development of vascular remodeling, we assessed 6 rats that underwent a single monocrotaline injection, chronic hypoxic exposure, or a combination of both treatments. Valproic acid or vehicle was administered in rats with severe PH induced by the combination method to assess whether valproic acid has the ability to prevent severe PH development in the first 3 weeks or to reverse disease progression at 3-5 weeks.

Results:
The combination method induced PH of greater severity than that induced by any single stimulation in rats after 3 weeks. Compared with the vehicle-treated rats, valproic acid treatment blocked the elevation of right ventricular systolic pressure and right ventricle hypertrophy index (from 57 ± 3 to 49 ± 3 mmHg and from 46 ± 4 to 37 ± 3 %) in both the first 3 weeks and in the late treatment group (from 75 ± 2 to 61 ± 5mmHg and from 61 ± 7 to 48 ± 3 %, respectively; P < 0.01). Valproic acid attenuated the muscularization ratio of peripheral pulmonary vascular, repressed proliferation and inflammation marker expression (PCNA and ED1), and enhanced apoptosis (cleaved caspase 3) in severe PH rats.

Conclusions:
These data indicate that a selective HDAC inhibitor may be effective in the treatment of PH.
Abstract 11763: Impact of Beta Blockade on Prognosis in Patients With Chronic Severe Degenerative Mitral Regurgitation
Authors: Hai Ofek Y , Khan Nasimullah , Supino Phyllis G , Herrold Edmund M , Hochreiter Clare , Borer Jeffrey S
Published: July 2021

Background:
The impact of chronic beta blockade (BB) on cardiac events (CE) in patients (pts) with chronic severe mitral regurgitation (MR) has not been studied by randomized trials but is inferred as beneficial from observational data. However a recent randomized preclinical study demonstrated increased mortality with BB in MR.

Methods:
We retrospectively analyzed 45 consecutive study-eligible pts (age 49±12 yrs, 69% male) with isolated chronic severe non-ischemic MR without concomitant coronary disease, followed through 19 yrs, to assess impact of chronic BB use at entry on CE (death or indications for valve surgery). At entry, all pts were non-hypertensive (HTN) and free of surgical indications; 9 pts chronically received BB at entry (of whom 7 continued receiving BB throughout the study period). CE rate differences were assessed by Kaplan-Meier log rank comparison; 6 pts on non-selective BBs were analyzed separately on an exploratory basis. Cox model analysis was used to adjust for variations in other baseline covariates (age, gender, etiology, other cardiac drugs).

Results:
During follow-up, CE included: sudden death (1), heart failure (8), a-fib (6), left ventricular (LV) dimensions (IDs)>4.5cm (11), LV ejection fraction (EF)<60% (6), right ventricular (RV) EF<35% (2), combination CE (7). CE risk was 2-fold higher among pts receiving BB (Avg annual risk [AAR]= 15.28%) vs. those not receiving BB (AAR= 33.04%) (p<.05) (Figure). A > 3-fold relative CE risk was observed when pts on selective BB were excluded (AAR: BB vs no BB = 56.18% vs. 15.28%, p=.01). BB effects remained statistically significant (p<.05) when analyses were adjusted for other baseline covariates.

Conclusions:
Contrary to earlier observational data, in our series BB appears to increase CE risk in pts
without
HTN. Further research including larger numbers of MR pts, preferably via randomized design, is needed to clarify the discrepancy between the different findings among existing studies.
Abstract 11773: Liver Transplant Candidates: To Stress or Not to Stress?
Authors: Ibrahim Ahmed , Schuster Andres , Alraies M Chadi , Sonny Abraham , Cywinski Jacek B , Jaber Wael A
Published: July 2021

Background:
The prevalence of coronary artery disease (CAD) in patients with end stage liver disease (ESLD) and the incidence of acute coronary syndromes (ACS) post liver transplantation (LT) remain controversial. Current AHA/ACC guidelines recommend non-invasive stress testing (NIST) for risk stratification of LT recipients based on conventional cardiovascular risk factors (CVRF). The aim of our study was to define the role of NIST in the pre-transplant evaluation of ESLD patients.

Methods:
We retrospectively reviewed the data of 366 patients who were referred to the Cleveland Clinic LT center between the years 2006 and 2008. We collected demographic data, CVRF, NIST, left heart catheterization (LHC) results, incidence of ACS and death.

Results:
In our study population, the mean age was 56±8 years, 68% were males, 83% Caucasian, 34% diabetic, 36% hypertensive, 22% smokers, 17% had hyperlipidemia, 11% known CAD, and 14% had family history of premature CAD; overall, 70% of the patients had at least 3 CVRF. Mean platelet count was 104±70 k/uL, mean INR 1.4 ±0.4, total cholesterol (TC) 143±45 mg/dL and 42% were on beta blockers (BB).

A total of 270 patients underwent NIST with dobutamine stress echocardiography (DSE) or nuclear stress testing. DSE was diagnostic in 76% of the cases and nuclear stress test was performed in 52% of the patients with a non-diagnostic DSE. From the patients with diagnostic NIST, 40 underwent LHC. There were 5 true positive, 22 true negative, 8 false positive, and 5 false negative results giving NIST a negative predictive value of 81%.

After a median follow-up of 6.2 years [IQR 3.4 to 6.7], 264 patients were transplanted, 9 patients developed an ACS and only one of them within the first year of LT. ACS was the cause of death in one patient which occurred more than 3 years from LT. All of these patients had a prior negative NIST. There were no ACS in the non-transplanted group.

Conclusions:
In our ESLD population, NIST had a limited role in the CV risk assessment of LT candidates. This is probably secondary to the low incidence of ACS which could be explained by inherent ESLD factors like thrombocytopenia, low TC, and elevated INR.
Abstract 11776: Relative Merits of Ejection Fraction and Strain by 2D Echo, 3D Echo and Cardiac Magnetic Resonance Imaging for Image-Based Recognition of Heart Failure
Authors: Saha Samir K , Toole Rena S , Kiotsekoglou Anatoli , Cao Jie J , Reichek Nathaniel , Gopal Aasha
Published: July 2021

Introduction:
Echo and cardiac magnetic resonance imaging (CMR) are often used in evaluation of patients with heart failure (HF) whether associated with systolic dysfunction or preserved ejection fraction (EF). We evaluated the relative merits of EF (by CMR and 2D echo) versus echo strain (by 2D and 3D speckle tracking echo STE) for imaged-based recognition of patients with HF.

Methods:
117 subjects (81 normals and 36 HF) were evaluated. There were no significant differences in age or gender between normals (59+/-14 yrs, 39 M) and HF (54+/-14 yrs, 29 M). 2D biplane echo and CMR provided EF while 2D and 3DSTE yielded global longitudinal (GLS %) and circumferential (GCS%) strains. Since 3DSTE was optimized for strain rather than EF, 3DEF was not evaluated. HF diagnosis was based on dyspnea, plasma N-terminal pro-B type brain natriuretic peptide and EF.

Results:
As expected, mean EF and strains differed between normals and HF (table). Using a backward elimination regression model, only 2DEF, CMREF, 2DGCS% and 3DGLS% were retained for further analysis. ROC-guided criterion values (for HF recognition) for 2DEF, CMREF, 2DGCS% and 3DGLS% were >52%, >50%, >-22% and >-16%, respectively. Using these values, the sensitivity, specificity, and odd-ratios for HF recognition with each parameter were computed (table).

Conclusions:
CMREF provided the highest sensitivity and specificity for HF recognition. The most sensitive echo measure was 3DGLS% while the most specific echo measure was 2DEF. However, in a mixed population of normals and HF, whether associated with systolic dysfunction or preserved EF, 2DGCS% and 3DGLS% had the highest odds ratios.
Abstract 11800: Optimal Coronary Revascularization in Patients With Unstable Angina or Non-ST-Elevation Myocardial Infarction: 5-Year Outcomes of the CREDO-Kyoto PCI/CABG Registry Cohort-2
Authors: Marui Akira , Kimura Takeshi , Nishiwaki Noboru , Mitsudo Kazuaki , Komiya Tatsuhiko , Hanyu Michiya , Shiomi Hiroki , Tanaka Shiro , Sakata Ryuzo ,   The CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators
Published: July 2021

Background:
SYNTAX trial revealed the long-term benefit of coronary artery bypass grafting (CABG) relative to percutaneous coronary intervention (PCI) using drug-eluting stent (DES) in patients with stable angina with complex coronary disease. However, long-term benefit of CABG relative to PCI in patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI) has not been well elucidated.

Methods and Results:
We identified 673 patients with 3-vessel and/or left main disease with UA or NSTEMI among 15,939 patients undergoing first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2 (PCI: n=425, CABG: n=238). Age was not different between the 2 groups (p=0.58). Rate of Killip class III or IV (pulmonary edema or cardiogenic shock) was not different between the 2 groups (14% vs. 11%, p=0.19). Number of treated lesion was higher in the CABG group (2.0±1.0 vs. 3.0±1.0, p<0.001). Pre-procedural SYNTAX score was significantly higher in the CABG group (26.8±10.8 vs. 32.2±10.5, p<0.001). Unadjusted 30-day mortality was 6.0% for PCI and 2.9% for CABG.

[Table] Five-year outcomes revealed that all-cause mortality after PCI was significantly higher than after CABG (hazard ratio [95% confidence interval]; 1.59 [1.15-2.21], p=0.005). The risk of composite of death, stroke, or myocardial infarction (MACCE) after PCI were also higher than after CABG (1.63 [1.23-2.16], p<0.001). In patients with 3-vessel disease without left main disease (n=465), the risks of death and MACCE after PCI were significantly higher than after CABG (1.59 [1.04-2.43], p=0.03 and 1.60 [1.10-2.34], p=0.01). Similarly the risks of death and MACCE after PCI were also higher than after CABG in patients with left main disease (n=208)

Conclusions:
In patients with UA or NSTEMI, 5-year outcomes revealed that CABG relative to PCI reduced the risk of death, MACCE, and any revascularization in the DES era both in patients with 3-vessel and left main disease.
Abstract 11814: Pulmonary Capillary Wedge Pressure as a Strong Predictor for Successful Outcome of Atrial Fibrillation Ablation: A Speckle Tracking Echocardiographic Study
Authors: Kaneda Mayumi , Kawasaki Masanori , Hirose Takeshi , Tanaka Ryuhei , Matsuoka Rieko , Nagaya Maki , Amano Kazuo , Goto Yoshiaki , Warita Shunichiro , Minatoguchi Shingo , Kojima Tai , Ono Koji , Watanabe Takatomo , Tanihata Shintaro , Noda Toshiyuki , Noda Toshiyuki , Watanabe Sachiro , Minatoguchi Shinya
Published: July 2021

Background:
Atrial fibrillation (AF) is associated with left atrial (LA) remodeling caused by LA pressure or volume (LAV) overload represented by the elevated left ventricular filling pressure or LA enlargement. Pulmonary capillary wedge pressure (PCWP) as well as LAV may be useful predictor for successful outcome of AF ablation. The aim of the study was to elucidate the most useful predictor for successful outcome in AF ablation including PCWP measured by a speckle tracking echocardiography (STE).

Methods:
We measured LAV, LA emptying function (EF), strain and strain rate (SR) by the STE during sinus rhythm before ablation in 137 patients with paroxysmal AF (61±10 years, 80 men) who underwent pulmonary vein isolation. The parameters were compared between non-recurrence (successful) group (n=107, age 61±11, sinus rhythm was continued for more than 1 year) and recurrence group (n=30, age 60±10). The estimated PCWP (ePCWP) was determined as 10.7 - 12.4 x log (active LAEF / minimum LAV), as we previously reported. LA stiffness was calculated as ePCWP/LA strain. We also measured PCWP and LA pressure by cardiac catheterization just before AF ablation in 59 patients.

Results:
The ePCWP was correlated with PCWP measured by cardiac catheterization (r=0.71, p<0.01). The ePCWP and maximum LAV before ablation in recurrence group increased compared with non-recurrence group (15±3 vs. 11±4 mmHg, and 58±15 vs. 49±15 ml/m2, respectively). LA total and active EF decreased, and LA stiffness increased in recurrence group (39±10 vs. 44±11%, 20±7 vs. 25±10% and 0.83±0.59 vs. 0.47±0.33). In multivariate analysis, ePCWP was independently associated with successful ablation best among LAEF, active EF, maximum LAV and ePCWP. Using 13 mmHg of ePCWP as a cutoff, the sensitivity and specificity for successful ablation were 77 and 73% and the positive and negative predictive value were 44 and 92% (AUC= 0.81).

Conclusion:
Elevation of ePCWP before AF ablation was the best predictor of AF recurrence after AF ablation. This suggested a strong relation between LV filling pressure and the progression of LA remodeling responsible for AF. The ePCWP estimated by STE is useful to predict the successful outcome of AF ablation.
Abstract 11867: Late Stroke Rates After Maze Procedure
Authors: Tsuneyoshi Hiroshi , Komiya Tatsuhiko , Shimamoto Takeshi
Published: July 2021

Introduction:
Late stroke can affect quality of life after cardiac surgery. Atrial fibrillation is the most common cardiac arrhythmia and raises the risk of stroke; however, the incidence of late stroke after the Maze procedure has not been determined.

Methods:
We conducted a retrospective review of 4021 patients who underwent cardiac surgery at our institution between 2000 and 2013.

Results:
Follow-up data were obtained from 88% of patients at a mean of 4.8±3.4 years. Among these patients, 2.4% (95/4021) experienced symptomatic late stroke (mean period after surgery was 55±35 months, and the mean age was 72±13 years). About 32% (30/95) of patient strokes were caused from atrial fibrillation, 2% (2/95) from hemorrhagic events, 3% (3/95) from cerebral artery diseases, and 63% (60/95) from unknown causes.

Among 345 of the 4021 patients who underwent the Maze procedure (Full Maze: 157, LA Maze: 132, PV isolation: 56), 70.5% have remained in sinus rhythm as of their last follow-up. Just 4.3% (15/345) of patients that underwent the Maze procedure had a late stroke during the follow-up period. Of the 15 patients who had a late stroke, 10 failed the Maze procedure and remained in atrial fibrillation. In 60% (9/15) of patients experiencing a late stroke after the Maze procedure, the LA appendage was not closed at the time of surgery.

Conclusions:
The cause of late stroke after cardiovascular surgery was atrial fibrillation in not less than 30% of patients. The incidence of late stroke after the Maze procedure was 4.3%, which was relatively low considering these patients had arrhythmia problems before the operation (2.4% of all cardiac patients experienced a late stroke). Unsuccessful cases of the Maze procedure and non-LA appendage closure were considered risk factors for late stroke. When patients have atrial fibrillation prior to surgery, we recommend a concomitant Maze procedure or at least LA appendage closure to reduce the incidence of late stroke.
Abstract 11884: Successful Preclinical Study of Microporous Covered Stents for Intracranial Aneurysms
Authors: Nakayama Yasuhide , Satow Tetsu , Hamano Eika , Funayama Marina , Mizuno Takeshi , Kawajiri Hidetake , Moriwaki Takeshi , Ishii Daizo , Hayashi Masataka , Tajikawa Tsutomu , Takahashi Jun
Published: July 2021

Introduction:
Treatment of large or giant cerebral aneurysms with broad neck is extremely difficult or carries high risks, even with clinical available surgical method or endovascular one using coils with the assistance of bare stents. We are developing microporous covered stents (Goodman, Japan) for the treatment of intracranial aneurysms. In this study, as a preclinical study, their performances were evaluated in three different in vivo animal models under reliability assurance system (RAS).

Methods and Results:
The covered stents were prepared using specially designed flexible balloon-expandable stents (CoCr; diameter; 3.5~5.0 mm, length; 16~28 mm) by dip-coating to cover their strut completely with polyurethane membrane (thickness; 20 μm) followed by laser-based microprocessing (pore size; 100 μm, opening ratio; ~30%). All animal experiments were performed under RAS. 1) In canine curved vessel model (5 mm in diameter), all stents mounted on the derivery catheter could smoothly pass the tortuous vessel with little arterial damage (n=10). 2) In canine sidewall aneurysm model, all post-immediate run showed disappearance of the aneurysm (over 7 mm in size, 4 mm in wide), and histological examination at 3 months revealed complete endothelialization at the aneurysmal neck and entirely organized aneurysm (n=20). 3) In rabbit aortic model (3 mm in diameter), just after placing a single stent lumbar arteries (less than 1 mm) were patent with good run-off. Even after placing the second stent in an overlapped fashion lumbar arteries are still patent. After 3 months, both the parent artery and branching lumbar arteries are patent in all cases (n=15). The safety of the covering material was guaranteed at over 2 years (n=10).

Conclusions:
Excellent embolization performance was confirmed in all cases even at the large and wide-necked aneurysms on the tortuous vessels with high reliability. Based on the obtained perfect preclinical results we are planning the first in human study of the covered stents for intracranial aneurysms in 2015.
Abstract 11977: Tranilast, Transient Receptor Potential Vanilloid 2 Antagonist, Ameliorates End-Stage Heart Failure of Mice With Dilated Cardiomyopathy
Authors: Iwata Yuko , Komamura Kazuo
Published: July 2021

Introduction:
Abnormal intracellular Ca2+ handling seems to be involved in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). We have found up-regulation of the expression of transient receptor potential vanilloid 2 (TRPV2), a calcium-permeable cation channel, in the sarcolemma of myocardium of animal and human DCM.

Hypothesis:
We hypothesized an orally active TRPV2 antagonist, tranilast, ameliorated heart failure symptoms of DCM mice.

Methods:
We used 4C30 mice (created by National Institute of Biomedical Innovation, Japan), which has abnormal myocardial calcium handling, as a model of DCM. Sixteen 4C30 mice of 25 weeks old with end-stage heart failure were given no drug (control) or 20 mg/kg/day of carvediol (group C) or 400 mg/kg/day of tranilast (group T) or both of them (group B) for 2 weeks.

Results:
Blood pressure and heart rate were similar among the 4 groups. Echocardiography demonstrated tranilast improved fractional shortening (in %). Control: 6.2±2.5; Group C: 14.2±5.6, NS; Group T: 16.6±2.3, p<0.05; Group B: 17.2±3.2, p<0.05. Tranilast also improved cardiac hypertrophy measured with heart-to-body weight ratio (HW/BW in mg/g). Control: 12.4±2.5; Group C: 11.5±3.4, NS; Group T: 8.6±0.9, p<0.05; Group B: 5.9±1.1, p<0.01. Sarcolemmal expression of TRPV2 measured with immunostaining in 4C30 mice increased twice as much as syngeneic C57BL/6J. Tranilast, not carvedilol, halved the expression of TRPV2, corresponding to reduction in [Ca2+]i of isolated cardiomyocytes. Consistent with those changes, CaMKII phosphorylation reduced in the 4C30 mice after treatment of tranilast.

Conclusions:
Tranilast ameliorated heart failure symptoms of 4C30 mice, possibly due to the inhibition of Ca2+ influx through TRPV2.
Abstract 11982: Circulating Invariant Natural Killer T Cells are Decreased in Patients With Chronic Heart Failure
Authors: Saito Akimichi , Ishimori Naoki , Nishikawa Mikito , Kinugawa Shintaro , Tsutsui Hiroyuki
Published: July 2021

Objective:
Inflammatory mediators play a crucial role in the development of chronic heart failure (HF). Invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes, which recognize glycolipid antigens and secrete a large amount of T helper (Th) 1/Th2 cytokines on activation, function as immunomodulatory cells in the various pathological processes. We have demonstrated that iNKT cells have a protective role against the development of left ventricular (LV) remodeling and failure after myocardial infarction in mice. However, it remains unclear whether iNKT cells are involved in the development of HF in humans.

Methods and Results:
Nine HF patients (NYHA II or III, LV ejection fraction 26.3±3.0%) and 8 healthy controls were studied. The mean age and male gender were comparable between HF and controls (51.2±5.1 vs. 45.1±4.5 years and 77.8 vs. 75.0%). The causes of HF were idiopathic dilated cardiomyopathy in 3, ischemic in 2, and others in 4 patients. Plasma BNP was significantly higher in HF than in controls (739.4±207.2 vs. 19.8±6.5 pg/mL,
P
<0.01). The number of circulating iNKT cells, identified by the positive-staining of Vα24-Jα18 T Cell Receptor by flow-cytometric analysis, was significantly lower in HF (747±85 vs. 1058±271 counts/mL,
P
<0.01). Its ratio to the total lymphocyte was also significantly lower (0.111±0.004 vs. 0.146±0.035%,
P
<0.01). Plasma interleukin-6 and high-sensitivity CRP were significantly higher in HF (3.99±0.86 vs. 0.78±0.14 pg/mL and 0.28±0.10 vs. 0.06±0.02 mg/dL, respectively, both
P
<0.01). LV ejection fraction (
r
=0.72,
P
<0.05) and plasma log BNP (
r
=-0.70,
P
<0.05) were significantly correlated to the ratio of iNKT cells among HF patients.

Conclusions:
Circulating iNKT cells were decreased in HF patients, suggesting that they have a potential role in the development of human HF.
Abstract 12001: CHA2DS2-VASc Score Are More Predictive of Clinical Outcomes Compared With SYNTAX Score in Patients With Coronary Artery Disease
Authors: Abe Daisuke , Sato Akira , Harunari Tomohiko , Misaki Masako , Kakefuda Yuki , Hoshi Tomoya , Aonuma Kazutaka
Published: July 2021

Purpose:
To investigate the association among clinical outcomes, clinical variables (CHA2DS2-VASc score), and anatomical variables (SYNTAX score) in patients undergoing percutaneous coronary intervention (PCI) with coronary artery disease (CAD).

Methods:
A cohort of 1701 patients (69.7±10.7 years old, 77% male) who underwent PCI for CAD was analyzed from ICAS (Ibaraki Cardiovascular Assessment Study) multi-center registry between April 2007 to April 2010. We divided patients into 3 groups according to tertile of SYNTAX score; Low SYNTAX (0-8: n=567), Mid SYNTAX (9-15: n=567), and High SYNTAX (≧16: n=567). And we also divide into 3 subgroups on the basis of CHA2DS2-VASc score (low: 0-2, mid: 3-5, high: 6-8 point). Clinical outcomes were defined as major adverse cardiovascular event (MACE) which included all cause death, myocardial infarction, stroke, or hospitalization for worsening heart failure.

Results:
Mean follow up period was 440 days. Incidence of MACE was significantly increased according to increasing CHA2DS2-VASc score in high and low SYANTAX groups (figure). There was no relation between increasing SYNTAX score and MACE in each CHA2DS2-VASc subgroups. Receiver operating characteristics curve (ROC) showed area under the curve (AUC) was larger in CHA2DS2-VASc score than SYNTAX score for MACE (0.613 vs. 0.498). CHA2DS2-VASc score was an independent predictor of MACE after adjustment of multiple cofounders (per increase, OR: 1.30, 95% confidence interval: 1.17-1.43, p<0.001), but not SYNTAX score (per increase, OR: 0.99, 95% confidence interval: 0.98-1.01, p=0.56).

Conclusion:
High CHA2DS2-VASc score provides worse clinical outcomes compared with SYNTAX score in patients with CAD in this registry.
Abstract 12010: The Pivotal Role of Pentraxin 3, a New Inflammatory Marker, in Hypertensive Failing Heart With Normal Ejection Fraction
Authors: Yamamoto Eiichiro , Kusaka Hiroaki , Hirata Yasuhiro , Tokitsu Takanori , Sueta Daisuke , Fujisue Koichiro , Kurokawa Hirofumi , Sugamura Koichi , Yasuda Osamu , Mitsuyama Shokei K , Ogawa Hisao
Published: July 2021

Background:
Long pentraxin 3 (PTX3) is known to be produced by various types of cell through a lot of inflammatory cytokines such as tumor necrosis factor (TNF)-α. PTX3 is therefore used as an inflammatory marker for acute myocardial infarction and heart failure (HF). However, the precise mechanism of PTX3 in the exacerbation of HF with normal l ejection fraction (HFNEF) remains to be elucidated.

Methods:
(1) Dahl salt-sensitive hypertensive rats (DS rats), which are the useful model of HFNEF, fed high-salt (HS) DS rats progressively develop hypertension and exhibit LV hypertrophy (LVH) a, followed by HFNEF. In the present study, we used HS loaded DS rats at the age of 15 and 20 weeks to elucidate the mechanism of transition from hypertensive LVH to HFNEF. (2) We examined the levels of PTX3 at the aortic root and the coronary sinus in HFNEF patients who received CAG during the study period.

Results:
(1) 20-week-old HS loaded DS rats were characterized by prominent LVH and marked LV relaxation abnormality but by the preserved LV systolic function. Compared with control DS rats fed low-salt (LS) diet, LV macrophage infiltration and interstitial fibrosis as shown by histological examination were already significantly increased at the stage of LVH, and remained increased up to the stage of HFNEF (P<0.01). In HS-loaded DS rats suffering from HFNEF, immunoreactivity to PTX3 was similarly localized with cardiac interstitial and perivascular fibrosis, and also expressed in infiltrating macrophages. On the other hand, real-time quantitative RT-PCR showed that cardiac TNF-α and PTX3 mRNA expression was not altered at the stage of LVH, but significantly increased at the stage of HFNEF compared with LS control DS rats, while cardiac transforming growth factor (TGF)-β and CTGF, collagen-related cytokines, significantly increased both at LVH and HFNEF stages. (2) In human, plasma levels of PTX3 at coronary sinus were significantly higher than aortic root in patients with HFNEF (n=11, P<0.01), but not different in normal patients (n=20, P=0.22).

Conclusion:
PTX3 produced from macrophage, rather than from cardiac fibroblasts, might be associated with transition from LVH to HFNEF. Taken together with human data, PTX3 could be a useful marker for discriminating HFNEF from LVH.
Abstract 12059: High Cardiorespiratory Fitness is Associated With Larger Coronary Artery Diameters
Authors: Ho John , Cannaday John , Finley Carrie , Barlow Carolyn , Wade Wendy , Reinhardt Dale , Ellis Joe , DeFina Laura , Gibbons Larry , Cooper Kenneth
Published: July 2021

Introduction:
Cardiorespiratory fitness is inversely associated with morbidity and mortality even after adjustment for traditional risk factors. The biological mechanism for the protective effect of high fitness is largely unknown.

Hypothesis:
We hypothesized that high fitness would be associated with larger coronary artery diameters independent of traditional risk factors.

Methods:
In this study, 500 men with a coronary artery calcium score (CACS) < 10 were evaluated, with 100 from each age-adjusted fitness quintile (very poor, 1-20%; poor, 21-39%; fair, 40-59%; good, 60-79%; and excellent, 80-100%). Each participant had undergone fitness assessment with an exercise treadmill test on the day of CACS. Blinded to the fitness category, one of us measured the proximal diameters of the left main (LM), left anterior descending (LAD), left circumflex (LCx), and the right coronary (RCA) arteries. Spearman correlations were calculated for the diameters of each coronary artery with treadmill time and for the sum of artery diameters with treadmill time. Linear mixed-effects regression was used to estimate the association between fitness and coronary artery diameters while adjusting for potential confounders.

Results:
Each coronary artery diameter (LM r=0.12, p=0.009; LAD r=0.11, p=0.02; LCx r=0.10, p=0.02; RCA r=0.18, p<0.0001) and the sum of artery diameters (r=0.19, p<0.0001) were positively correlated with fitness after adjusting for body surface area. The RCA diameter and the sum of artery diameters remained positively correlated with fitness after further adjusting for traditional risk factors. In multivariate analyses, men in the highest fitness quintile had significantly larger coronary artery diameters compared to those in the lowest fitness quintile [β=0.85 mm (SE=0.27)]. A positive linear trend was observed across fitness quintiles and the LM (p=0.008), LAD (p=0.05), RCA (p<0.0001) diameters, and the sum of coronary artery diameters (p=0.0003). When examined continuously, each minute increase in treadmill time was associated with larger diameters (β=0.08 mm (SE=0.02) p<0.001).

Conclusion:
Higher fitness is positively associated with larger coronary artery diameters.
Abstract 12062: Patient and Caregiver Heart Failure Symptom Response Behaviors in 364 Patient-Caregiver Dyads
Authors: Bidwell Julie T , Vellone Ercole , Lyons Karen S , Hiatt Shirin O , Alvaro Rosaria , Riegel Barbara , Lee Christopher S
Published: July 2021

Introduction:
Recognition and response to symptoms of heart failure (HF) is critical to reducing the risk of hospitalization and mortality. Although many patients have support from caregivers, little is known about caregivers’ contributions to HF symptom response behaviors. We hypothesized that patient-, caregiver-, and dyad-level factors would be associated with better symptom response behaviors.

Methods:
This was a secondary analysis of data on 364 Italian HF patient-caregiver dyads. HF symptom response behaviors were measured using patient and caregiver versions of the Self-Care of Heart Failure Index (0-100; higher = better). Health status (SF-12) and relationship quality (single item) were collected from patients and caregivers. Patient cognition and comorbidities were measured using the MMSE and Charlson Index. Caregiver social support was measured with the Carers of Older People in Europe Index. Hospitalizations were abstracted from the medical record. Multilevel modeling was used for all analyses.

Results:
Patients were older (age 76.3±10.8 years), predominantly male (57.3%) and most had NYHA Class II/III HF (72.2%). Caregivers were younger (age 57.7±14.6 years), and most were female (51.7%) and adult child (53.6%) or spousal (34.0%) caregivers. Symptom response behaviors were poor in patients (49.1±19.6) and caregivers (54.7±18.3). Patient gender (male β=-4.60±1.92, p<0.05), better cognition (β=0.40±0.19, p<0.05), worse caregiver health (β=-0.43±0.14, p<0.01), and higher relationship quality (β=2.28±0.83, p<0.01) were significant determinants of better patient symptom response. Nonspousal relationship (β=6.62±1.96, p<0.001), fewer patient comorbidities (β=-2.32±0.79, p<0.01), better patient health (β=0.41±0.12, p=0.001), more hospitalizations (β=3.06±1.41, p<0.05), higher relationship quality (β=2.12±0.84, p<0.01), and higher caregiver social support (β=1.09±0.43, p<0.05) were significant determinants of better caregiver symptom response.

Conclusions:
Combinations of individual and relationship factors were significant determinants of patient and caregiver responses to HF symptoms. Assessment of patient and caregiver as a dyad may be useful in evaluating risk for poor management of HF symptoms.
Abstract 12081: Glycemic Variability as Determined by a Continuous Glucose Monitoring System Predicts Left Ventricular Dysfunction in Patients With a First ST-Segment Elevation Myocardial Infarction
Authors: Gohbara Masaomi , Iwahashi Noriaki , Kataoka Shunsuke , Akiyama Eiichi , Maejima Nobuhiko , Tsukahara Kengo , Hibi Kiyoshi , Kosuge Masami , Ebina Toshiaki , Umemura Satoshi , Kimura Kazuo
Published: July 2021

Background:
Glycemic Variability (GV) may play an important role in development of cardiovascular disease however the clinical significance of GV is not fully understood in patients with ST-segment elevation myocardial infarction (STEMI). We explored the clinical utility of GV using continuous glucose monitoring system (CGMS; iPro2, Medtronic, USA).

Methods:
Seventy-four patients (66 males, 63±12 years) with a first STEMI were enrolled. STEMI was de[[Unable to Display Character: ﬁ]]ned as chest pain lasting for at least 30 minutes accompanied by ST-segment elevation and an increase in the serum peak-creatine phosphokinase (CPK) level to more than twice the upper limit of normal. All patients were equipped with a CGMS 1 week after admission and GV was assessed by measuring the Mean Amplitude of Glycemic Excursion (MAGE) during 24 hours with 3 regular meals. At 7 month, all patients underwent conventional 2D echocardiography and blood sampling (BNP; brain natriuretic peptide) to explore the effect of GV to their cardiac function.

Results:
On univariate analysis male, culprit left anterior descending artery (LAD), peak CK-MB and MAGE were predictors of decreased left ventricular ejection fraction (LVEF). On multivariate analysis higher MAGE level was an independent predictor of decreased LVEF. Higher MAGE level was also an independent predictor of higher BNP level at 7 month.

Conclusions:
GV was an independent predictor of left ventricular dysfunction in patients with a first STEMI.
Abstract 12091: Novel ECMO Cannulation Strategy Expedites Conversion to LVAD
Authors: Foley Lisa S , Reece T. B , Brieke Andreas , Ambardekar Amrut , Cleveland Joseph C , Babu Ashok N , Fullerton David A
Published: July 2021

Objectives:
Venoarterial (VA) ECMO has emerged as a successful modality for bridging patients with critical cardiogenic shock to durable support. However, LV distention on ECMO impairs RV and lung recovery and can result in the need for a temporary RVAD. Additionally, patients on VA ECMO with organ dysfunction may require ongoing LV assistance for recovery prior to durable LVAD conversion. Placement of a large apical LV vent allows bedside conversion to LVAD and provides time for organ recovery prior to elective durable device implantation.

Hypothesis:
We hypothesized that LV venting on ECMO accelerates RV recovery, hastening conversion to LVAD.

Methods:
ECMO cases from January 2012 to April 2014 were reviewed following IRB approval. Sixteen patients met INTERMACS Category 1 criteria who were placed on VA ECMO for cardiogenic or post-cardiotomy shock. Eight patients had LV venting and eight had standard peripheral cannulation. Refractory pulmonary edema, CPR during cannulation, and severe LV distention were indications for LV venting. A 32 French malleable cannula was placed by limited anterolateral thoracotomy into the LV apex. Bedside LVAD conversion was performed by percutaneous decannulation of the venous line and removal of oxygenator from circuit.

Results:
Conversion to temporary LVAD was successful in all LV vent cases at a mean timepoint of 5.9 (±1.3) days after LV venting compared with 13.5 (±4.9) days in non-vented patients (p = 0.07). RVAD requirement was 25% in non-vented patients and 0% in vented patients. 30-day mortality was 25% for both groups.

Conclusions:
LV venting as an adjunct to VA ECMO facilitates RV recovery to enable early LVAD conversion at the bedside. It also provides organ recovery time and obviates the need for a temporary RVAD at the time of durable LVAD implantation. In conclusion, the LV apical venting technique allows staged recovery of critically ill patients in biventricular and multiple organ failure with a high survival rate.
Abstract 12096: Temporal Trends in Ischemic Stroke and Anticoagulation Therapy Among Medicare Beneficiaries Having Non-Valvular Atrial Fibrillation With and Without Diabetes Mellitus, 1992-2010
Authors: Shroff Gautam R , Solid Craig A , Herzog Charles A
Published: July 2021

Background:
Patients with diabetes mellitus (DM) and non valvular atrial fibrillation (AF) are at increased risk of ischemic stroke; but evidence regarding ischemic stroke and warfarin use in the literature is limited. We evaluated temporal trends in ischemic stroke and warfarin use among the US Medicare population with and without DM.

Methods:
One-year cohorts of patients with Medicare as primary payer, 1992-2010, were created using the Medicare 5% sample. ICD-9-CM codes were used to identify AF, ischemic and hemorrhagic stroke and comorbidities; ≤3 consecutive prothrombin-time claims were used to identify warfarin use.

Results:
Demographic characteristics between 1992 (n=40255) and 2010 (n=80314) respectively were (proportions): age 65-74 years (37%, 32%); age ≤ 85 years (20%, 25%); white (94%, 93%); hypertension (46%, 80%); DM (20%, 32%), chronic kidney disease (5%, 18%). Ischemic stroke rates among Medicare AF patients with DM decreased by 71% (1992, 2010) from 65 to 19 /1000 patient-years; warfarin utilization increased from 28% to 62% respectively (Figure 1A). Among Medicare AF patients without DM, ischemic stroke rates decreased by 68% from 44 to 14/ 1000 patient-years; warfarin use increased 26% to 59% respectively (Figure 1B). About 38% Medicare AF pts with DM did not receive anticoagulation in 2010.

Conclusion:
Medicare patients with and without DM had a similar reduction in ischemic stroke rates; and similar increase in warfarin utilization over the study period. A significant proportion of Medicare pts with DM did not receive anticoagulation with warfarin for AF in 2010; this population deserves future attention.
Abstract 12099: Activated Notch1 Interacting With LKB1 Reduces Myocardial Ischemic Injury via Modulating AMPK Signaling Pathway
Authors: Yang Hui , Sun Wanqing , Ma Yina , Chen Xingchi , Techiryan George , Li Ji
Published: July 2021

Introduction:
The activation of the intrinsic AMP-activated protein kinase (AMPK) pathway plays an important role in the myocardial response to ischemia, pressure overload, and heart failure. The Notch1 signaling in the adult myocardium is activated transiently in response to myocardial injury, and it has implicated that Notch1 signaling may contribute to cardiac repair. However, the role of Notch1 signaling in myocardial infarction remain uncertain.

Hypothesis:
The cardioprotective AMPK signaling pathway could mediate the beneficial effects of Notch1 signaling cascade during myocardial infarction.

Methods:
C57BL/6J male mouse hearts were subjected
in vivo
to left anterior descending coronary artery ligation for 5 min, 20 min, 24 hr, 1 week and 2 weeks. Mice were treated with dibenzazepine (DBZ), a new Notch γ-secretase inhibitor (5 μmol/kg/day, i.p.) and the vehicle groups were treated with saline. Ischemic heart tissues were harvested for protein, mRNA expression and histologic analysis.

Results:
The Notch1 signaling was significantly activated during myocardial ischemia
in vivo
(p<0.05 vs. sham group). Interestingly, in the
ex vivo
heart perfusion system, systemic administration of DBZ to hearts led to significantly increase of myocardial infarct size and apoptosis caused by myocardial ischemia (p<0.05 vs. vehicle group). The immunoblotting results demonstrated that DBZ treatment significantly inhibited the AMPK activation by myocardial ischemia (p<0.05 vs. ischemia alone). Further immunoprecipitation experimental data showed that activated Notch1 strongly interacts with one AMPK upstream kinase, LKB1, to form a complex that modulates cardiac AMPK activation during myocardial ischemia. Moreover, the inhibition of Notch1 by DBZ impaired AMPK activation that significantly increased inflammation response such as activation of c-Jun N-terminal protein kinase (JNK) and NF-κB signaling during myocardial ischemia.

Conclusions:
The activated Notch1 signaling interacts with LKB1 to trigger the activation of cardioprotective AMPK signaling during myocardial ischemia. The Notch1-LKB1-AMPK signaling cascade could be a potential pharmacologic mimic for cardioprotection of ischemic heart disease.
Abstract 12147: Heart Failure With Preserved and Reduced Ejection Fraction in Middle Eastern Arab and South Asian Patients Hospitalized in a Middle-Eastern Country (1991-2013)
Authors: Salam Amar M , AlBinali Hajar , Singh Rajvir , Al-Qahtani Awad , Asaad Nidal , Al-Suwaidi Jassim
Published: July 2021

Objectives:
The epidemiology of patients with heart failure (HF) remains largely unexplored in some ethnicities. The aim of the current study was to examine the clinical characteristics, treatment and in-hospital outcomes of Middle Eastern Arabs and South Asian patients hospitalized with HF in a Middle-Eastern Country and compare different subsets of patients according to the degree of left ventricular (LV) dysfunction using a large national registry.

Methods:
Retrospective analysis of patients hospitalized with HF in Qatar from January 1991 through June 2013 was made. Patients were divided into 3 groups according to LV ejection fraction (EF) on echocardiography; HF with preserved EF (HFpEF)= EF ≥50%, HF with reduced EF (HFrEF)= EF≤40%, and (HFpEF, borderline)= EF 41-49%. Patients risk profiles, management and in-hospital outcomes were compared in the 3 groups.

Results:
During study period 3114 patients were hospitalized with HF; 637(20.5%) with HFpEF, 415(13.3%) with (HFpEF, borderline) and 2062(66.2%) with HFrEF. Patients with HFpEF were the oldest in age, had the highest body mass index and the highest rates of associated atrial fibrillation and valvular heart disease. Patients with (HFpEF, borderline) had the highest rates of hypertension, diabetes mellitus, chronic kidney disease, dyslipidemia, old myocardial infarction and associated acute coronary syndromes whereas patients with HFrEF had the highest rates of smokers [Table]. There were no significant differences in the length of hospital stay among the 3 groups while the in-hospital mortality was significantly highest among patients with HFrEF.

Conclusions:
The current study explored for the first time HF in Middle Eastern Arabs and South Asian ethnicities according to the degree of LV function. HFrEF was the commonest class accounting for two thirds of hospitalizations with HF and was associated with higher in-hospital mortality. Further studies with long term follow-up data are warranted.