bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16025: Continuous Positive Airway Pressure Therapy as a Therapy for Cardiac Arrhythmias: Meta - Analysis of 14 Studies
Authors: Qureshi Waqas , Nasir Usama b , Ali Zeeshan , Qadir Shayan , Hayat-Syed Muhammad K , Alqalyoobi Shehabaldin , Mawri Sagger , Al-Mallah Mouaz H
Published: July 2021

Introduction:
Obstructive sleep apnea (OSA) is a risk factor for cardiac arrhythmias. Continuous positive airway pressure (CPAP) as a therapy of these arrhythmias is not well established.

Hypothesis:
We performed a meta-analysis of prospective cohort studies and randomized controlled trials to evaluate effect of CPAP on cardiac arrhythmias.

Methods:
MEDLINE, EMBASE, Cochrane databases, GoogleScholar and WebofScience from inception to June 2014 were searched for prospective cohort and intervention studies reporting that had CPAP as intervention and cardiac arrhythmia as an outcome measure. Two authors independently assessed study quality and extracted data. Random effects model was used to estimate pooled effect of CPAP on burden as well as number of events of cardiac arrhythmias. Between-study heterogeneity was assessed by I2 method.

Results:
Ten prospective cohort studies and four randomized controlled trials were included. There were a total of 1246 individuals that underwent CPAP therapy and 1213 were in comparison group. In random-effect models, CPAP was associated with decreased risk of cardiac arrhythmia (pooled Risk Ratio 0.62; 95% CI 0.41 - 0.93, p = 0.02) as well as burden of cardiac arrhythmia (mean difference in electrocardiographic abnormality -14.6; 95% CI -23.6 - -5.7, p = 0.002). Significant heterogeneity was present in studies (I2 = >90%). Type of cardiac arrhythmia (atrial vs. ventricular) explained most of the heterogeneity; with greater effect of CPAP on reducing atrial rather than ventricular arrhythmia. Forest plots are given in the figure.

Conclusions:
CPAP appears to be effective in treatment of cardiac arrhythmia in OSA patients. The effect is greater for atrial arrhythmia than ventricular arrhythmia. Long term studies evaluating this effect on mortality are needed.
Abstract 16043: The Role of eNOS Signaling in Wound Healing in a Murine Model of Diet-Induced Obesity
Authors: Haberzettl Petra , McCracken James , Hill Bradford G , Bhatnagar Aruni , Conklin Daniel J
Published: July 2021

Background and Rationale:
Type 2-diabetes is associated with the depletion of circulating endothelial progenitor cells (EPCs) and deficits in wound healing; conditions that have been linked to decreased activity of endothelial nitric oxide synthase (eNOS). However, it is not clear how, in the context of insulin resistance, increasing eNOS would affect EPC levels and wound healing. Therefore, we measured EPC levels and recovery from hind-limb ischemia (HLI) in wild-type and eNOS-transgenic (Tg) mice in a model of diet-induced obesity.

Methods and Results:
Wild-type (WT) C57BL/6 and eNOS-Tg mice were placed on a low (LFD) or high fat diet (HFD). After 12 weeks, the mice were subjected to HLI, and tissue perfusion was assessed by Laser Doppler Imaging. Levels of EPCs (Flk-1+/Sca-1+-cells) were measured by flow cytometry. HFD feeding, for 4-12 weeks, decreased circulating EPC levels while the levels of EPCs in the bone marrow were increased. Insulin (100 nM; 15 min) stimulated Akt and eNOS phosphorylation in aorta of LFD, but not HFD-fed mice, indicating insulin resistance. HFD decreased plasma NOx levels and activated the pro-inflammatory NF-κBα pathway in aorta, heart, liver, skeletal muscle and adipose tissue as analyzed by Western blot analysis. Recovery of blood perfusion, 2 weeks after HLI, was significantly higher in LFD than HFD-fed mice (76±3% vs. 21±4%; p<0.05, n=5). Overexpression of eNOS prevented HFD-induced vascular insulin resistance, and enhanced recovery from HLI in both LFD (+64±4%) and HFD (+17±7%) fed mice. HLI decreased circulating EPC levels by about 30% in WT mice, while no changes in EPC levels were found in eNOS-Tg mice. Bone marrow EPCs were reduced after HLI in eNOS-Tg (28±8% of sham), but not in WT (94±27% of sham), mice.

Conclusions:
HFD impairs recovery from HLI, which may be related in part to vascular insulin resistance and decreased EPC mobilization. Deficits in the wound healing response due to diet-induced obesity could be overcome by increasing NO production via eNOS. Treatment strategies to increase NO bioavailability could promote wound healing in diabetic patients and prevent diabetic complications such as critical limb ischemia.
Abstract 16094: Association of Diurnal Blood Pressure Variation and Nocturnal Hypoxia in Patients With Cardiovascular Risk Factors: Japan Morning Surge-Home Blood Pressure (J-HOP) SAS Study
Authors: Shimpo Masahisa , Hoshide Satoshi , Nagai Michiaki , Eguchi Kazuo , Kario Kazuomi
Published: July 2021

Introduction:
Abnormal diurnal blood pressure (BP) variation, such as riser or extreme-dipper, is known as risk factors of target organ damage and subsequent cardiovascular events. Nocturnal hypoxia due to sleep apnea syndrome (SAS) is likely to influence diurnal BP variation and risk increase; however, little has been evaluated in large scale cohort in Asian population.

Hypothesis:
We assessed the hypothesis that diurnal BP variation is associated with nocturnal hypoxia in high risk Japanese patients.

Methods:
The study subjects were 1087 participants of the J-HOP Study with one or more cardiovascular risk factors (n=4019). Pulse oximetry oxygen saturation (SpO2) was measured with a validated device (PULSOX Me-300; Teijin Pharma, Tokyo, Japan) simultaneously with ambulatory BP monitoring (ABPM).

Results:
The frequency of each diurnal BP variation are as follows; dipper (normal circadian rhythm) 42.8%, non-dippers 34.6%, extreme-dipper 13.2%, riser 9.4%. When assessed by 3% oxygen desaturation index (ODI; times/h), 14.2% of patients showed 3%ODI≥15 (suspected moderate sleep apnea), and 2.8% of patients showed 3%ODI≥30 (suspected severe sleep apnea). The likelihood of coexisting severe sleep apnea (3%ODI≥30) was significantly higher (5.9%) in patients with riser pattern compared with that in dipper pattern (1.9%) (odd ratio 3.17; 95%CI 1.10-9.11, p<0.03). Three percent ODI was significantly higher in patients with riser pattern than that in dipper pattern (6.6 vs 5.1 times/h; p=0.01). Furthermore, the patients in the longest time spent with SpO2 <90% category in quintiles had an increased likelihood of extreme-dipper pattern compared with those in the shorter categories (odds ratio 1.71; 95%CI 1.10-2.65; p<0.03).

Conclusion:
Abnormal diurnal BP variation was associated with nocturnal hypoxia in patients with cardiovascular risk factors. For the patients with riser or extreme-dipper pattern, further evaluations are recommended to detect higher risk patients with nocturnal hypoxia, such as SAS, heart failure or chronic pulmonary diseases.
Abstract 16108: Right Ventricular Strain is a More Sensitive Marker of Right Ventricular Dysfunction Than Right Ventricular Ejection Fraction in a Cohort of Patients With Idiopathic Pulmonary Arterial Hypertension
Authors: Grapsa Julia , Tan Timothy C , Dawson David , Nihoyannopoulos Petros
Published: July 2021

Introduction:
Strain has been shown to be more sensitive that ejection fraction in detecting subclinical dysfunction in the left ventricle. A number of echocardiographic parameters associated with right heart size and function have been shown to be impaired in idiopathic pulmonary arterial hypertension (IPAH) but there is minimal data on which may be the most sensitive.

Aim:
To characterize the changes in functional and echocardiographic indices of right ventricular (RV) size and function, in a cohort of IPAH patients followed serially to determine if strain is a more sensitive measure of RV dysfunction than RVEF.

Methods:
Thirty patients (24 women, mean age 46.8 ± 5.3 years) with newly diagnosed IPAH were prospectively recruited and followed with serial transthoracic echocardiograms (TTE; Philips Medical Systems, Andover, MA) 6 monthly for up to 18 months. A range of 2D and 3D echocardiographic measures of right ventricular dimensions and function, including right ventricular ejection fraction (RVEF) and systolic longitudinal strain (LS), was assessed at each time point after commencing treatment using vendor independent software (TomTec, Germany). Functional status was assessed at18 months. Statistical analyses were performed using JMP statistical package (SAS Institute In. Cary, NC)

Results:
3D RV volumes, ejection fraction, mass, 2D global strain and 2D free wall strain all show significant changes over 18 months (p-value < 0.05; ANOVA of repeated measures) although peak tricuspid regurgitant velocity, RV systolic pressure and stroke volume do not. However, RV global strain and RV free wall strain showed significant changes within 6 months after diagnosis but not RVEF, peak TR velocity or RVSP. The degree of change in the RV free wall strain change at 18 months but not RVSP, RV mass or RVEF, was also associated with an abnormal 6 min walk test (18 months change, p=0.03).

Conclusion:
RV global and free wall strain demonstrate significant decreases prior to RVEF, peak TR velocity and RVSP hence may be more more sensitive measures of RV dysfunction in patients with IPAH. These results may help guide treatment decisions and highlight the potential value of echocardiography in detecting subacute cardiac pathology.
Abstract 16122: Percutaneous Transluminal Balloon Angioplasty Ameliorates Metabolic and Renal Dysfunctions Associated With Hemodynamic Improvement in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Tatebe Shunsuke , Sugimura Koichiro , Nochioka Kotaro , Miura Masanobu , Yamamoto Saori , Yaoita Nobuhiro , Sato Haruka , Satoh Kimio , Shimokawa Hiroaki
Published: July 2021

Background:
Insulin resistance, dyslipidemia and renal dysfunction have been regarded as poor prognostic factors for pulmonary hypertension. We and others have recently demonstrated that percutaneous transluminal pulmonary angioplasty (PTPA) markedly improves pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this study, we examined whether PTPA also improves metabolic and renal impairments in CTEPH patients.

Methods and Results:
From April 2012 to May 2013, we examined serum levels of lipids and fatty acids fractions and plasma levels of glucose and immunoreactive insulin in 68 consecutive patients with CTEPH (64±14[SD] years, M/F 13/55) and calculated the homeostatic model assessment of insulin resistance (HOMA-IR). Renal function was assessed by estimated GFR (eGFR) and urinary albumin-to-creatinine (U-A/C) ratio. Vascular stiffness was evaluated by cardio-ankle vascular index (CAVI). The measurements were repeated after PTPA in 49 patients. Among the 68 patients, we noted NYHA functional class ≥III in 17, 6 min-walk distance <300m in 15, and cardiac index <2.0l/min/m
2
in 18, and regarding metabolic disorders, hypertension in 41, diabetes in 6 and dyslipidemia in 24. Insulin resistance (defined as HOMA-IR >2.0) was noted in 29 out of 63 (58%). Regarding renal function, eGFR was 61.6±17.8 ml/min/m
2
, U-A/C ratio 80.8±214.7mg/gCre, and chronic kidney disease in stage ≥3 was noted in 32 patients (47%). We performed PTPA in 49 patients (mean 3.3 essions/patient), which markedly improved NYHA functional class (P=0.008), 6min-walk distance (102±25 m, P<0.0001) and mean pulmonary arterial pressure (-9.9±1.3 mmHg, P<0.0001). Furthermore, PTPA significantly improved metabolic profiles such as HDL-chol (6.2 ±2.2 mg/dl, P=0.01), EPA (18.3±6.2 mg/dl, P=0.006), fasting blood sugar (-8.0±3.5 mg/dl, P=0.04), HbA1c (-0.3±0.1 %, P<0.0001) and CAVI (-0.44±0.23, P=0.02) . PTPA also significantly improved eGFR (5.2±1.2 ml/min/m
2
, P <0.001) and U-A/C ratio (-47.1±18.9 mg/gCre, P=0.004).

Conclusions:
These results indicate that metabolic and renal dysfunctions are commonly present in CTEPH patients and that PTPA markedly improves those disorders in addition to pulmonary hemodynamics.
Abstract 16131: Novel Magnetic Resonance Wave Intensity Analysis in Pulmonary Hypertension
Authors: Quail Michael A , Knight Daniel S , Steeden Jennifer A , Taelman Liesbeth , Moledina Shahin , Taylor Andrew M , Segers Patrick , Coghlan J. Gerry , Muthurangu Vivek
Published: July 2021

Background:
Pathological pulmonary wave reflections (WR) are a potential hemodynamic biomarker for pulmonary hypertension (PH). WR can be quantified using wave intensity analysis (WIA), typically utilizing simultaneous invasive pressure and velocity measurements. In this study we reformulated WIA to use CMR area and flow to measure reflections non-invasively. We hypothesized that this method could detect differences in WR in PH patients compared to healthy controls and could also differentiate certain PH subtypes.

Methods:
20 patients with PH (35% CTEPH), mean age 54years (75% female) and 10 healthy controls, 47years (60% female) were recruited. Branch pulmonary artery (PA) flow volume (Q) and area curves (A) were used to measure wave intensity (
dI
), defined as,
dI
=[[Unable to Display Character: ∆]]Ax[[Unable to Display Character: ∆]]Q and
dI
±
=±
c
/4 [[[Unable to Display Character: ∆]]A± [[Unable to Display Character: ∆]]Q/
c
]
2
, where
c
=wave-speed. Data were acquired using a retrospectively gated, respiratory navigated, golden-angle, 10.5ms temporal resolution, phase-contrast MR sequence. All patients also underwent right heart cardiac catheterization for pressure and vascular resistance (PVR) measurement, median interval 6 days (IQR 2-11days). The presence of proximal clot in CTEPH patients was determined from contemporaneous CT/angiographic data.

Results:
A backwards-travelling compression wave (BCW) was present in both left and right PAs of all PH patients, but was absent in all controls (
p
=6e
-8
). A backwards-travelling expansion/suction wave was present in the 19/20 branch PAs of controls, and only 4/40 PAs in patients (
p
< 0.0001). The area under the BCW was associated with a sensitivity of 100% (95% CI 63-100%) and specificity of 91% (95% CI 75-98%) for the presence of clot in the proximal pulmonary arteries of patients with CTEPH.

Conclusions:
Noninvasive pulmonary WIA accurately delineates pulmonary vascular health and disease. The main findings of this study were: i) There was a significant difference in WIA metrics between patients and controls, in particular, the presence of a BCW was specifically associated with the presence of PH; and ii) The magnitude of the BCW area showed discriminatory capacity for the presence of proximal PA clot in patients with CTEPH. We believe that these results demonstrate that WIA could be used in the non-invasive assessment of PH.
Abstract 16133: High Density Lipoprotein Cholesterol is an Alternative Marker to Troponin for Acute Coronary Syndrome in High Risk Patients
Authors: Nguyen Anke , Adams Heath , Yap Natalie , Gin Julian , Wilson Andrew M
Published: July 2021

Introduction:
It is well known that high density lipoprotein cholesterol is inversely correlated with the risk of coronary artery disease. However, data is limited regarding the relationship of high density lipoprotein cholesterol in the acute setting of coronary artery disease and particularly how it compares to the most well-known biomarker, cardiac troponin I.

Hypothesis:
We assessed the hypothesis that high density lipoprotein cholesterol could be used as an alternative marker to troponin for acute coronary syndrome (ACS) in high risk patients.

Methods:
We analysed 740 patients of the BRAVEHEART cohort presenting for coronary angiography at our institution between October 2009 and March 2014. Of these, 153 patients presented with ACS, including 44 with ST elevation myocardial infarction and 109 with non-ST elevation myocardial infarction, and 587 patients presented without ACS. Binary logistic regression was used to compare high density lipoprotein cholesterol and cardiac troponin I levels as predictors of ACS, independent of age, sex, cardiac risk factors and statin use.

Results:
Patients presenting with ACS had higher median cardiac troponin I levels (0.34 vs. 0.02 μg/L; p<0.001), higher median serum triglyceride levels (1.5 vs. 1.3 mmol/L, p<0.001) and lower median high density lipoprotein cholesterol levels (0.97 vs. 1.09 mmol/L, p<0.001) than patients without ACS. There was no difference in total cholesterol and low density lipoprotein cholesterol between the two groups. After adjusting for differences in patient variables, the strongest independent predictors of ACS were cardiac troponin I (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.24-1.82; p<0.001) and high density lipoprotein cholesterol (OR, 0.12; 95% CI, 0.04-0.36; p<0.001).

Conclusion:
In conclusion, high density lipoprotein cholesterol was found to be an independent marker of ACS in high risk patients at our institution. Further studies on high density lipoprotein cholesterol could determine its clinical use in conjunction with troponin levels in patients presenting with ACS.
Abstract 16144: The Impact of Ventricular Pacing for Elderly Patients With Pacemaker Implantation: Over One Decade and Large Cohort Analysis
Authors: Kamijima Ayako , Ishibashi Kohei , Wada Mitsuru , Nakajima Ikutaro , Miyamoto Koji , Okamura Hideo , Noda Takashi , Aiba Takeshi , Kamakura Shiro , Kusano Kengo
Published: July 2021

Introduction:
Previous studies showed that ventricular pacing (VP) increased the cardiac event of patients with pacemaker (PM). However, these studies consisted of patients under 75 years old and the influence of VP for elderly patients (over 75 years old) is still unclear. We sought to evaluate long-term effect of VP for elderly patients.

Methods:
A total of 782 patients (mean 57.2 years old) underwent PM implantation for brady-arrhythmia were enrolled from 1978 to 2005. The elderly patients (199 patients, over 75 years old, mean 80.7 years old) and all patients were divided into VP and non-VP group, and evaluated adverse events (death or readmission for heart failure).

Results:
The mean follow-up period was 10.1 years and 84 elderly patients (42%) developed adverse events. Kaplan-Meier analysis revealed that (1) VP increased the adverse event in all patients. (2) There was no significant difference in the adverse events of elderly patients between VP and non-VP group (Fig).

Conclusion:
VP may be tolerated for elderly patients with PM, whereas VP has no effect for the prognosis.
Abstract 16189: Lineage Tracing of Postnatal Cardiomyogenic Progenitor Cells
Authors: Liu Yuan-Hung , Huang Shih-Yun , Lin Yi-Shuan , Huang Hsing-Yu
Published: July 2021

Recent studies report that postnatal mammalian hearts undergo cardiomyocyte refreshment. While the exact origin of the cells involved in postnatal cardiomyogenesis remains unclear.

Here, we identified a pool of Nkx2.5 enhancer expressing cells in the postnatal mouse heart with cardiomyogenic differentiation potential in vitro. We tracked the expression of a cardiac-specific enhancer of Nkx2.5 using inducible Nkx2.5 enhancer-Cre mice from embryonic development to adulthood and post-myocardial infarction (MI) and documented the Nkx2.5 enhancer expressing cells directly contribute to postnatal cardiomyogenesis in vivo. Upon genetic ablation of these activated progenitors after myocardial injury, the cardiac function deteriorated. Transcriptomic analysis of Nkx2.5 enhancer expressing cells showed high expression of heart development genes.

To trace the developmental origin of the activated Nkx2.5 cardiomyogenic progenitor cells, we created different lineage-Cre/Nkx2.5 enh-eGFP/ROSA26 reporter triple transgenic mice. Post-MI Nkx2.5 cardiomyogenic progenitor cells originated from the embryonic epicardial cells, not from the pre-existing cardiomyocytes, endothelial cells, cardiac neural crest cells, or perinatal/postnatal epicardial cells.

Together, this study confirmed that cardiac lineage-specific progenitor cells, which originate from embryonic epicardium-derived cells, contribute to postnatal mammalian cardiomyogenesis.
Abstract 16190: National Trends in RSV Hospitalizations in Children With Hemodynamically Significant Heart Disease, 1997-2009
Authors: Chu Patricia Y , Hornik Christoph P , Li Jennifer S , Campbell Michael J , Hill Kevin D
Published: July 2021

Background:
Children with hemodynamically significant heart disease (HS-HD) are at risk for morbidities and mortality due to respiratory syncytial virus (RSV). Palivizumab was approved for RSV prophylaxis in 1998. Guidelines released in December 2003 recommend palivizumab for all children < 2 yrs with HS-HD. We sought to define the impact of RSV prophylaxis in children with HS-HD by evaluating trends in U.S. RSV hospitalizations.

Methods:
The 1997, ’00, ’03, ’06 and ’09 Healthcare Cost and Utilization Project (HCUP) Kids’ Inpatient Databases (KID) were used to estimate U.S. RSV hospitalizations in children < 2 yrs, overall and in those with HS-HD, using standard HCUP weighting methods. RSV was defined by ICD-9-CM codes for RSV infection. HS-HD was defined using ICD-9-CM codes from the Clinical Classifications Software for congestive heart failure, or an ICD-9-CM code for pulmonary hypertension, common truncus, common ventricle, or hypoplastic left heart syndrome.

Results:
Our cohort included an estimated 461,491 RSV hospitalizations; 2,132 in children with HS-HD. Figure 1 depicts hospitalizations over time. There was no evident trend in number of overall RSV hospitalizations, however RSV hospitalizations in children with HS-HD declined by 39% from ’97 to ‘09. The largest decline was from ’97-’03. RSV hospitalizations in children with HS-HD relative to overall hospitalizations in children with HS-HD declined annually from ’97-’06 with a small increase in ‘09 (3.8%, 3.5%, 3.0%, 2.3% and 2.6% for successive analytic years). In 2009 mean hospital length of stay for children with HS-HD and RSV was 22.5 ± 2.1 days.

Conclusions:
RSV disease burden in children with HS-HD has declined since palivizumab approval. Much of this decline occurred before palivizumab was recommended for use in HS-HD, perhaps reflecting early adoption of prophylaxis, or greater awareness of alternative preventative strategies. RSV remains a significant cause of morbidity in children with HS-HD.
Abstract 16202: Changes in Hemoglobin After Pulmonary Artery Catheterization: Results From the ESCAPE Trial
Authors: Damluji Abdulla , Macon Conrad , Al-Damluji Mohammed , Fox Arieh , Marzouka George R , Gilchrist Ian C , Cohen Mauricio G , Moscucci Mauro
Published: July 2021

Introduction:
We sought to investigate the association between hemoglobin (Hgb) changes in patients with ADHF (with and without PACs) to mortality and clinical outcomes.

Methods:
We examined 433 patients enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Change of Hgb (g/dL) was defined as at least 1 (g/dL) drop by hospital discharge. Quartiles of % change of Hgb (g/dL) were calculated. We used multivariable Cox regression analysis to evaluate the effect Hgb change on mortality and composite end points of death, cardiac re-hospitalization, or cardiac transplant.

Results:
Of the 433 patients, 324 (75%) had baseline and discharge Hgb available for analysis. Of those, 64 (20%) had at least 1 (g/dL) drop of Hgb by time of discharge. Patients in the Hgb drop group were older than those without Hgb changes (59 vs. 55, p = 0.011). There were no baseline differences in gender, race, and etiology of HF between groups. Compared to patients without Hgb changes, patients with Hgb drop had lower systolic BP (99 vs. 106, p = 0.017), lower sodium (136 vs. 137, p =0.025), higher BUN (37 vs. 26, p <0.001), and higher Creatinine (1.6 vs. 1.3, p <0.001), respectively. Higher Hgb drop was observed in the PACs (vs. no PACs) randomized arm of the trial (2 g/dL: PACs 10% versus 3%, p =0.010; 3 g/dL: PACs 5% versus 0%, p =0.005). After adjustments, higher in-hospital Hgb was associated with lower mortality (HR 0.79, p =0.003). In addition, patients in the Hgb drop group had increased risk of mortality (Adjusted HR 2.38, p =0.003) and composite endpoints (Adjusted HR 1.43, p =0.055). PACs insertion was not associated with adverse clinical outcomes by quartiles of % change of hemoglobin (Mortality: Q1: HR 0.80, p 0.601, Q2 HR 0.79, p = 0.706, Q3 HR 0.34, p =0.101, Q4 HR 2.23, p =0.357).

Conclusion:
In-hospital decrease in Hgb is independently associated with increased long-term mortality and adverse cardiovascular events in severe HF. The ideal Hgb levels in ADHF patients should be investigated and the insertion of PACs to direct therapy should be weighed against bleeding risks.
Abstract 16205: Validation Study of the Quantified Frequency Domain Optical Coherence Tomography Analysis for the Detection of Erythrocyte-Rich Thrombus
Authors: Shiratori Yoshitaka , Watanabe Masato , Suzuki Nobuaki , Ishikawa Shuichi , Watanabe Yusuke , Kyono Hiroyuki , Kondo Fukuo , Fukusato Toshio , Kozuma Ken , Isshiki Takaaki
Published: July 2021

Introduction:
Frequency domain optical coherence tomography (FDOCT) can evaluate erythrocyte-rich thrombus, containing more inflammatory cells and reflect high thrombus burden, leading to impaired myocardial reperfusion in myocardial infarction patients.

Hypothesis:
The purpose of this study was to validate the quantified FDOCT signal analysis in evaluating the erythrocyte-rich thrombus with ex-vivo materials.

Methods:
We evaluated 55 specimens of coronary artery thrombus obtained by thrombectomy from 9 patients with acute coronary syndrome. The thrombi were immersed in saline immediately after the thrombectomy and FDOCT image acquisition was performed. Quantitative FDOCT analysis for all contiguous frames was performed by the dedicated automated software (OCT system software, Light Lab Inc.). In each sample, signal intensity and normalized standard deviation of signal (NSD) were evaluated quantitatively for a frame showing the biggest thrombus area. All thrombi were stained with hematoxylin-eosin, and the cellular component of erythrocyte were stained using monoclonal antibodies against a protein specific to erythrocyte membranes (glycophorin-A). Computer-assisted analysis was performed using dedicated software (WinROOF, Mitani Corp., Tokyo, Japan) for color identification of the erythrocyte area.

Results:
Erythrocyte-rich thrombus (n=26), defined as %erythrocyte area (erythrocyte area/total area X100)≧67%, showed higher [NSD / mean signal intensity X100] than white thrombus (n=21), defined as %erythrocyte area<33% (4.14±0.67 vs. 3.62±0.73, p=0.016). The optimal cut-off point of [NSD/mean signal intensity X100] for prediction of erythrocyte-rich thrombus was 4.20 (sensitivity: 50.0%, specificity: 81.9%, area under the receiver operating characteristic curve: 0.67, respectively).

Conclusions:
This study showed the utility of quantified FDOCT signal analysis on the evaluation of erythrocyte-rich thrombus.
Abstract 16237: Zero Fluoroscopy Ablation of Atrial Fibrillation: A Safety and Feasibility Study
Authors: Di Biase Luigi , Horton Rodney , Trivedi Chintan , Mohanty Prasant , Mohanty Sanghamitra , Bai Rong , Sanchez Javier , Gallinghouse G. Joseph , Zagrodzky Jason , Al-Ahmad Amin , Hranitzky Patrick , Burkhardt J. David , Natale Andrea
Published: July 2021

Introduction:
Radiofrequency catheter ablation of atrial fibrillation is performed under fluoroscopic guidance and therefore carries radiation risk exposure for the both the patient and the operator. Three-dimensional mapping systems and newer technologies to allow non-fluoroscopic catheter visualization together with intracardiac echo have reduced but not abolished the fluoroscopy exposure. We aim to demonstrate the feasibility, the safety and the efficacy of catheter ablation for atrial fibrillation without the use of fluoroscopy.

Methods:
A totally fluoro-less approach was developed for AF ablation at our Institution.

94 consecutive AF patients underwent zero fluoroscopy catheter ablation for atrial fibrillation. In the zero fluoroscopy cases, the fluoroscopy arm was kept far away from the patient table. Access including double trans-septal, mapping with the Carto 3 system and ablation were all performed without fluoroscopy with the use of ICE and the Carto 3 system. These 94 patients were compared with 94 control patients matched for age, sex and type of AF who underwent AF ablation by the same operator with the use of fluoroscopy.

Results:
Baseline characteristics were similar between fluoroless (N=94, Age=64.5 ± 10.1, 75.5% male, 48% paroxysmal) and control (N=94, Age=65.1 ± 9.9, 72.3% male, 50% paroxysmal) group. Non-PV triggers were detected and ablated in 51 (54.3%) and 56 (59.6%) patients in fluoroless and control group respectively (p=0.5). Average fluoro time in control group was 10.1 ± 4.7 minutes. Procedure duration was comparable (120.4 ± 25.8 vs. 122.2 ± 28.7, p =0.6). After the short term median follow-up of 4.5 (4 – 6.5) months, 10 (10.6 %) patients in flourless and 9 (9.6%) patients in control group experienced recurrences (p=0.8).One pericardial effusion requiring pericardiocenteis occurred in the fluoroless group.

Conclusions:
Our series show that zero fluoroscopy ablation of atrial fibrillation with the use of newer technologies is feasible, safe and efficacious at the short term follow up. Importantly in our series the double transeptal was performed without fluoroscopy and the ablation was not limited to the pulmonary veins only but included ablation of the posterior wall, the coronary sinus and the left atrial appendage.
Abstract 16263: Stress Myocardial Perfusion Imaging in Myocardial Bridging
Authors: Sunder Suraj , Bishu Kalkidan , Miller Todd , Anavekar Nandan
Published: July 2021

Introduction:
The physiologic relevance of myocardial bridging (MB) that is found on invasive (ICA) and CT coronary angiography (CTA) is not known. Myocardial perfusion imaging (MPI) may be useful in objectively assessing altered myocardial blood flow associated with MB. We studied the prevalence of ischemia on MPI and mortality among patients with MB.

Methods:
Patients with MPI studies within 6 months of MB identified on ICAs (2002-2014) or CTAs (2005-2014) at the Mayo Clinic were retrospectively studied. Exclusion criteria included a history of myocardial infarction (MI), coronary artery bypass grafting and hemodynamically significant coronary artery disease (CAD, coronary artery stenosis ≥ 50%) were excluded.

Results:
1116 individuals had MB on ICA out of which 300 had MPI studies. 511 individuals had MB on CTA out of which 63 had MPI studies. After excluding patients with CAD, 114 patients with MB identified on ICA and 31 patients with MB identified on CTA remained for analysis. Patients in the ICA and CTA cohort were the same age (60±13 years for ICA vs 60±12 years for CTA cohort, p=0.9). The ICA cohort was likely to include smokers (47 vs 26%, p=0.03) and those with hyperlipidemia (67 vs 45%, p=0.03). The prevalence of ischemia on MPI was similar in the ICA and CTA cohorts (42 vs. 44%, p=0.5). After a median follow-up of 1166 days, the ICA cohort had 12 patient deaths (8%). There was no death in the CTA cohort. The presence of ischemia on MPI was not associated with increased mortality on long-term follow-up (Log Rank p=0.9).

Conclusions:
Ischemia on MPI is commonly found in patients with MB who do not have significant CAD. While patients with MB identified on ICA are more likely to have traditional CAD risk factors, the prevalence of ischemia on MPI was similar when compared to patients with MB on CTA. In this small retrospective study, ischemia identified on MPI was not associated with increased mortality.
Abstract 16295: Human Epicardial Bipolar Electrograms Prolong and Reduce in Amplitude Prior to Induction of Peri-Operative Atrial Fibrillation and Are Related to Sites of High Electrogram Dominant Frequency in Sinus Rhythm
Authors: Zaman Junaid , Harling Leanne , Athanasiou Thanos , Peters Nicholas S
Published: July 2021

Background:
The exact trigger/substrate interactions leading to post-operative AF are unknown. Sites of high DF in sinus rhythm are proposed to harbor ‘fibrillar myocardium’ or ‘AF nests’. We studied AF inducibility related to putative upstream substrate changes by characterising epicardial electrograms (EGM) in both time and frequency domains.

Method:
AF naïve patients (n=14) undergoing coronary artery bypass grafting (CABG) had bipolar electrograms recorded from the lateral right atria (RA) wall with a high density spiral catheter, sampled at 1kHz. RA burst pacing at cycle lengths (CL) of 200, 500 and 1000ms was performed with any episodes of AF > 30s recorded. Electrograms were analysed using an average of 5 consecutive beats for duration, peak to peak amplitude, dominant frequency (DF) and activation time at all bipole pairs during every pacing drive train (total EGMs analysed 3430).

Results:
Bipolar EGM duration was significantly longer during AF (mean = 76.64ms, SD = 29.35ms) than all other CLs or NSR (p<0.0001). There was no difference between CLs but a trend to longer EGM at 200ms CL. EGM amplitude was significantly smaller during AF (mean = 0.85mV, SD = 0.51mv) vs. 500ms CL and NSR (p<0.0001) and at 200ms vs. 500ms CL (p<0.05) and NSR (p<0.0001). The EGM DF was significantly lower in AF (mean = 75.87Hz, SD = 23.63Hz) vs NSR (mean = 89.33Hz, SD = 25.99Hz) (p<0.05) but not vs. pacing CLs. Activation time was significantly prolonged at 200ms CL (mean = 29.41ms, SD = 16.23ms) vs AF and NSR (p<0.001 and 0.05 respectively).

Conclusions:
Human bipolar EGMs prolong and reduce in amplitude in induced peri-operative AF than in NSR or pacing. Atrial activation slows at 200ms CL, prior to initiation of AF. These changes are accompanied by high DF sites in NSR which may reveal underlying ‘AF nests’ even in non-remodelled atria. These novel peri-operative electrophysiological findings suggest upstream substrate changes which may predispose patients to post-operative AF.
Abstract 16317: Cost-Effectiveness of Bi-Ventricular Pacemakers vs. RV Pacemakers and Bi-Ventricular Defibrillators vs. Dual Chamber Defibrillators in Patients With Atrioventricular Block and Systolic Dysfunction: All-Patient and Subgroup Analyses From the BLOCK-HF Clinical Trial
Authors: Adamson Philip B , Chung Eugene S , St. John Sutton Martin G , Sidhu Manpreet K , Mealing Stuart , Padhiar Amie , Tsintzos Stelios I , Bril Sarah L , Lautenbach Amy A , Curtis Anne B
Published: July 2021

BACKGROUND:
The cost-effectiveness (C-E) of biventricular (BiV) pacing compared to right ventricular (RV) pacing in patients with a pacing indication due to atrioventricular (AV) block and EF < 50% is unknown. Material differences may exist between the C-E of BiV pacemakers (BiV-P) vs. RV and BiV defibrillators (BiV-D) vs. dual chamber ICDs, the latter when patients independently have an ICD indication.

METHODS:
Patient-level data from the BLOCK-HF trial were used. Statistical models were used to predict all-cause mortality, NYHA distribution over time, and NYHA-specific HF-related healthcare utilization (HCU) rates. Analyses were undertaken separately for BiV/RV (All-Patient), BiV-P/IPG and BiV-D/ICD.

RESULTS:
HCU rates in NYHA Classes I/II were lower than Classes III/IV and consistently reduced with BiV devices. Predicted life expectancy in the “All-Patient” analysis was 6.78 years with RV devices and 7.52 with BiV ones (a 10.8% increase). More BiV patients were predicted to remain in, or improve to, Classes I/II, if alive. In the “All-Patient” analysis, BiV offered patients 0.41 more Quality-Adjusted Life Years (QALYs) compared to RV, at an additional cost of $12,537 (Incremental C-E Ratio “ICER” $30,860.16/QALY Gained). Within the clinical co-variate subgroups of the “All-Patient” analysis, the highest ICER observed was $43,687.59 (NYHA Class I Patients). Within the device-based subgroups, BiV-D patients were projected to benefit more (0.84 years gained) than BiV-P ones (0.49 years)

CONCLUSIONS:
BiV reduces HCU rates compared with RV, offering survival benefits and slowing HF progression. The “All-Patient” ICER was $30,860.16/QALY Gained and ICERs were consistently below the conventional US acceptability threshold ($50,000/QALY Gained). The additional cost associated with offering BiV devices to patients with AV block and systolic dysfunction appears justified by the expected benefits across both device types.
Abstract 16362: Early Cardiology Assessment and Intervention Reduces Mortality Following Myocardial Injury After Non-Cardiac Surgery (MINS)
Authors: Hua Alina X , Pattenden Holly , Leung Maria , Davies Simon , George David A , Raubenheimer Hilgart , Niwaz Zakiyah , Lim Eric
Published: July 2021

Myocardial injury after non-cardiac surgery (MINS) has been recently defined as troponin elevation ≥0.03ng/ml, associated with 3.87 fold increase in early mortality (1). We sought to determine the impact of early cardiology intervention on 30-day mortality in patients who underwent general thoracic surgery and developed MINS.

Methods:
A retrospective review of patients who underwent thoracic surgery over a 5-year period where troponin levels were routinely measured on the first post-operative day was performed. Data acquisition and mortality status was obtained via medical records and NHS tracing systems. Thirty-day mortality was compared on the MINS cohort using Fisher’s exact square testing and logistic regression analysis. Actuarial survival was calculated using Kaplan Meier method and Cox proportional hazards regression was utilized to determine risk adjusted impact of MINS on post-operative survival.

Results:
Troponin levels were measured in 492 (96%) of 511 patients and 80 (16%) had troponin elevation fulfilling MINS criteria. Of the MINS positive patients, 61 (76%) received early cardiology consult and a formal diagnosis of “myocardial infarction” stated in 4 (5%). Risk assessment for Acute Myocardial Infarction was performed in all patients and 20 (25%) commenced on anti-platelet agents, 4 (5%) on β-blockers and 1 (1%) underwent primary coronary intervention. In total, 49 (61%) received primary risk factor modification and 26 (33%) had further cardiology outpatient follow-up.

There were no significant differences in the proportion who died within the first 30 days in the MINS group (2.6%) compared to the non-MINS group (1.6%; P=0.625). The odds ratio for 30-day mortality in the MINS group was 1.69 (95% CI 0.34 to 8.57, P=0.522). On follow up there were no significant difference on the impact of MINS on survival between the two groups (HR 1.06 95% CI 0.67 to 1.68; P=0.799).

Conclusion:
Our results confirm MINS is common after general thoracic surgery. We observed that early cardiology intervention reduced the expected hazard ratio of early death from 3.87 to an odds ratio of 1.69 with no significant difference in either early or longer term mortality for patients who developed MINS.
Abstract 16378: Growth Differentiation Factor-15 Independently Predicts 2 Year Mortality in Patients With Acute Coronary Syndrome: Observations From the A to Z Trial
Authors: Kosova Ethan C , de Lemos James A , Jarolim Petr , Guo Jianping , Braunwald Eugene , Sabatine Marc S , Morrow David A
Published: July 2021

BACKGROUND:
Growth Differentiation Factor-15 (GDF-15) is an inflammatory biomarker upregulated in the setting of myocardial stress that we and others have shown to have potential prognostic value in cardiovascular (CV) disease. However, any role for GDF-15 along with traditional CV risk factors and biomarkers in predicting long term mortality after ACS remains investigational.

METHODS:
We measured the plasma concentration of GDF-15 after stabilization of ACS in 4,179 patients (pts) presenting with UA/NSTEMI or STEMI enrolled in the A to Z Trial. Established, pre-specified cutoffs of GDF-15 (<1200, 1200-1800, and >1800 ng/L) were used for analysis. Outcomes were followed through the end of the study (median 2 years).

RESULTS:
Pts with GDF-15 >1800 ng/L had significantly higher 2 year mortality rates than those with levels of 1200-1800 or <1200 ng/L (14.8%, 9.7%, and 3.2%, respectively; P<0.001, Fig-1A). After adjusting for age, sex, hypertension, diabetes, renal function, STEMI vs NSTEACS, heart failure, B-type natriuretic peptide (BNP) and C-reactive protein (CRP), pts with GDF-15 >1800 ng/L were at a significantly higher risk of death at 2yr (HR 1.88; 95% CI, 1.25-2.83) compared to those with GDF-15 levels <1200 ng/L. Even in pts with low baseline BNP levels (<80 pg/mL), a GDF-15 level >1800 ng/L was associated with higher mortality risk compared with pts with levels of 1200-1800 or <1200 ng/L (11.8%, 7.9%, and 3.0% respectively; P<0.001, Fig-1B). Addition of GDF-15 to a model including traditional cardiovascular risk factors, BNP, and CRP resulted in significant net reclassification improvement (P<0.001).

CONCLUSIONS:
GDF-15 obtained in patients with established CAD stabilized after ACS is independently associated with increased mortality at 2 yrs. GDF-15 identifies additional mortality risk not currently captured by cardiovascular risk factors, BNP, or CRP. This finding supports GDF-15 as a potential aid for prognostic assessment in patients with ACS.
Abstract 164: Antithrombotic Use and Bleeding in Patients Receiving Therapeutic Hypothermia
Authors: Ryan Avery Kathleen , O’Brien Molly H , Silverman Michael G , Seethala Raghu , Chase Annmarie , Daddio Pierce Carol , Griswold Karen , Henderson Galen V , Hirning Beth Anne , Kyller Michael , Massaro Anthony F , Morrow David A , Stone Peter H , Strojwas Stefan , Szumita Paul M , Scirica Benjamin M
Published: July 2021

Background:
The known anticoagulant effects of hypothermia poses challenges when considering therapeutic hypothermia (TH) after cardiac arrest, including the risk of bleeding and the safety of giving concomitant antiplatelet and anticoagulation therapy. We therefore examined antithrombotic use and the risk of bleeding in patients receiving TH.

Methods:
In a large tertiary academic center in Boston, we examined the incidence of bleeding in patients evaluated for TH. Antiplatelet therapy and anticoagulation (oral or parenteral) prior to arrest and during the hospitalization were recorded.

Results:
TH was initiated in 190 patients and completed in 150. Among 40 patients in which TH was stopped early, bleeding was cited as a reason in 5 (though in 3 cases bleeding was documented at time of TH initiation). Of the 150 ‘completers’, 16 (10.6%) bled during TH. Bleeding was present at the time of TH initiation in 8/16 patients. Bleeding sites were most commonly GI 56.3% and vascular access 25% with no cases of intracranial bleeding. Presenting rhythm, survival, neurological outcomes and inpatient administration of antiplatelet and anticoagulation medications were similar between the bleeding and non-bleeding groups. Though there was no significant hematocrit change in the two groups, more patients with bleeding received red blood cell (RBC) transfusions (56.3% vs 2.2%) and received more RBC units (5.4±5.4 vs 1.3±0.5 p=0.054). Of the 15 patients on mechanical circulatory support, only 4 had a bleeding event during TH.

Conclusion:
There were no significant differences between the bleeding and non-bleeding groups during TH in terms of concomitant antithrombotic agents or neurologic recovery/survival. These findings suggest that the incidence of bleeding in TH is acceptable and that it is safe to treat patients with antithrombotics and mechanical circulatory devices as clinically indicated.
Abstract 16405: Long-Term Biological Pacemaker Activity Created by Percutaneous
TBX18
Gene Transfer
Authors: Hu Yu-Feng , Dawkins James , Cho Hee Cheol , Marbán Eduardo , Cingolani Eugenio
Published: July 2021

Background:
Minimally-invasive
TBX18
gene transfer creates physiologically-relevant biological pacemaker (BioP) activity for at least 2 weeks in pigs with complete heart block, providing evidence for therapeutic somatic reprogramming in a clinically-relevant disease model (Hu et al,
Sci Trans Med
2014). It remains unknown how long biological pacemaker activity is maintained after
TBX18
gene transfer.

Hypothesis:
We tested whether
TBX18
gene transfer could create sustained BioP activity beyond two weeks.

Methods:
Adenoviral vectors expressing either
TBX18
(n=3) or GFP (n=2) as a control were delivered into the high right ventricular septum via injection catheters (NOGA™ Myostar). Rate and rhythm were followed continuously for one month by implanted telemetry, and backup device utilization was quantified by serial pacemaker interrogations. Physical activity was measured by a built-in accelerometer.

Results:
BioP activity was evident in
TBX18
-transduced animals and persisted at least for 4 weeks. At week 4, maximal heart rate (HR,101±8 vs. 65±3bpm, p<0.05), daytime HR (79±4 vs. 53±1bpm, p<0.05), and electronic pacemaker utilization (82±3 vs. 6±3%, p<0.05) were higher in
TBX18
-transduced animals compared to GFP controls. Mean HR was borderline higher in
TBX18
-transduced animals compared to GFP controls (HR=70±7 vs. 51±1bpm, p=0.11) as was night-time HR (70±5 vs. 51±0bpm, p=0.07). Mean daily activity tends to be greater in
TBX18-
transduced group (394±18 vs. 339±12 A.U, p=0.11). There were no significant differences of ventricular arrhythmia incidence between the two groups during 4 week follow-up. Cardiac enzymes, liver function, renal function, and systemic inflammatory markers remained unchanged in both groups during follow-up.

Conclusions:
TBX18
gene transfer can create stable BioP activity for at least 4 weeks, suggesting a potential long-term BioP effect after adenoviral gene transfer.
Abstract 16416: Non PV Triggers Ablation Improves the Success Rate of Catheter Ablation of Persistent Atrial Fibrillation After a Single Procedure: Results From a Prospective Multicenter Study
Authors: Di Biase Luigi , Trivedi Chintan , Mohanty Prasant , Mohanty Sanghamitra , Bai Rong , Santangeli Pasquale , Sanchez Javier , Horton Rodney , Gallinghouse G. Joseph , Zagrodzky Jason , Hao Steven , Hongo Richard , Beheiry Salwa , Lakkireddy Dhanujaya R. , Reddy Madhu , Viles-Gonzalez Juan F. , Burkhardt J. David , Natale Andrea
Published: July 2021

Introduction:
Catheter ablation of persistent atrial fibrillation (AF) has a lower success rate when compared to paroxysmal AF patients. Whether in persistent AF patients ablation of the pulmonary vein antrum and posterior wall is sufficient to achieve long term freedom from AF is debated in the literature. We investigated if the ablation on non pv triggers from first procedure in addition to PV and posterior wall(PW) isolation could improve the procedural success rate.

Methods:
622 consecutive pts with persistent AF undergoing the first AF ablation were analysed and divided into 2 groups according to their ablation strategy. In group 1, pulmonary vein plus posterior wall ablation was performed (n=203) while in group 2 pulmonary veins plus posterior wall plus sustained and non sustained non pv triggers as disclosed by isoproterenol challenge were ablated. (n=419). All patients were followed up with intensive holter and event monitoring.

Results:
Clinical baseline characteristics were not statistically different between groups. After 17.8 ± 8.8 months follow-up, 118(58.1%) Group I and 283 (67.5%) Group II patients were free from any atrial tachyarrhythmias (log-rank p= 0.027). After adjusting for age, gender and clinically relevant variables, PVI and PW ablation alone was associated with significantly high recurrence. (Hazard ratio: 1.4, 95% Confidence Interval = 1.1– 1.8, p=0.02). Further, Group I patients undergoing redo procedure after a failed ablation had more NPV trigger Group II (80% vs 60%, p = 0.002, respectively, figure), while the number of patients with PV reconnection were similar between groups (65% vs. 64%, p=1.0).

Conclusions:
The results of our study shows that after a single procedure the ablation of non PV triggers, improves the long-term success rate in patients with persistent AF.