bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11079: Medical Therapy Leads to Positive Remodeling 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 distinct form of cardiomyopathy that can lead to progressive cardiac dysfunction and clinical heart failure. LVNC with left ventricular dilation or dysfunction is associated with a greater risk for mortality.

Hypothesis:
We hypothesized that initiation of heart failure medications in patients with LVNC and ventricular dysfunction, with or without dilation, would improve systolic function and reduce ventricular dilation.

Methods:
The study was a retrospective chart review. Inclusion criteria were as follows: presence of LVNC, reduced systolic function [Left ventricular ejection fraction (EF) < 55% or shortening fraction (SF) < 30%], therapy with at least one medication (beta blocker, ACE inhibitor, ARB), imaging performed both pre- and post-initiation of therapy.

Results:
Fifty one patients met inclusion criteria. Forty eight had complete echocardiographic data and 8 had complete cardiac MRI data. Mean age at initiation of medication was 11.5 ± 11.8 years. Follow-up, defined as time from initiation of medication to most recent echocardiogram, was 2.4 ± 2.3 years. Three patients (6%) were solely on a beta blocker, 15 (29%) were on ACE/ARB monotherapy, and 33 (65%) were on dual therapy with a beta blocker and an ACE/ARB. After initiation of medical therapy 38/44 (86%) had improvement in EF by ≤ 5%, 27/40 (68%) had improvement in their SF by ≤ 5%, 6/44 (14%) had no change in EF, and 11/40 (28%) had no change in SF. No patient (0/44, 0%) had a decline in EF by ≤5%, but 2/40 (5%) had a drop in SF by ≤ 5%.

A two-sided paired t-test was performed comparing EF, SF, and left ventricular end-diastolic dimension (LVEDD) in the cohort before and after therapeutic intervention demonstrating a 16 ± 12% improvement in EF (p < 0.0001), an 8 ± 9% improvement in SF (p < 0.0001), and a 0.83 ±1.93 (p<0.05) decrease in LVEDD z-score.

Conclusions:
Early diagnosis and medical treatment of LVNC with reduced systolic function leads to favorable left ventricular remodeling evident by an improvement in left ventricular systolic function and reduction of LVEDD.
Abstract 11138: Simplified Rheumatic Heart Disease Screening Criteria for Handheld Echocardiography
Authors: Lu Jimmy C , Sable Craig , Ensing Gregory J , Webb Catherine C , Scheel Janet , Aliku Twalib , Godown Justin C , Beaton Andrea
Published: July 2021

Background:
Using 2012 World Heart Federation (WHF) criteria, standard portable echocardiography (SPE) reveals a high burden of rheumatic heart disease (RHD) in resource poor settings, but widespread screening is limited by cost and physician availability. Handheld echocardiography (HHE) may decrease costs, but WHF criteria are complicated for rapid field screening, particularly for non-physician screeners.

Objective:
To determine the best simplified screening strategy for RHD detection using HHE.

Methods:
HHE (GE Vscan) and SPE (GE Vivid q or i or Philips CX-50) were performed in 5 schools in Gulu, Uganda. Borderline or definite RHD cases were defined by 2012 WHF criteria on SPE images, by 2 experienced readers. HHE studies were reviewed by cardiologists blinded to SP results. As HHE lacks continuous wave Doppler, pansystolic mitral regurgitation (MR) was defined as MR on 2 consecutive frames. We evaluated single and combined HHE parameters to determine the simplified screening strategy that maximized sensitivity and specificity for case detection.

Results:
In 1420 children (10.8±2.6 years old, 47% male) with HHE and SPE studies, morphologic criteria and presence of any MR by HHE had poor specificity (Table). MR jet length by HHE correlated with SPE (r=0.54, p<0.0001). Aortic insufficiency (AI) was specific but not sensitive. Combined criteria of MR jet length ≥1.5 cm, chosen from receiver operating characteristic analysis, or any AI best balanced sensitivity and specificity; pansystolic MR could be substituted for MR jet length with slightly lower sensitivity for definite RHD. With a prevalence of 4% and subsequent SPE screening of positive HHE studies, this would reduce SPE studies by 80% from a SPE-based screening strategy.

Conclusions:
In resource-limited settings, HHE with simplified criteria offers reasonable sensitivity and specificity for RHD screening. Further study is needed to validate HH screening by local practitioners and long-term outcomes.
Abstract 11295: Sonoreperfusion Therapy for Microvascular Obstruction Using Microbubbles and Low Dose tPa
Authors: Roos Sebastiaan T , Yu Francois T , Chen Xucai , Kamp Otto , van Rossum Albert C , Villanueva Flordeliza S , Pacella John J
Published: July 2021

Background:
Despite successful epicardial recanalization in acute myocardial infarction, adequate microvascular perfusion often fails due to embolization of thrombotic debris causing microvascular obstruction (MVO). We previously reported that long tone burst high mechanical index ultrasound (US) + microbubbles (MB) restored microvascular perfusion (sonoreperfusion, SRP) in an
in vitro
flow model using PBS perfusate. We sought to demonstrate SRP efficacy in whole blood perfusate with and without low dose tPa.

Methods:
The model comprised a 4 mm diameter phantom vessel with a 40 μm pore mesh to simulate a microvascular cross section and upstream pressure reflecting thrombus burden. Bovine whole blood and 2x10
6
/ml lipid MB (~3 μm) infused at 0.75 ml/min simulated microvascular flow. Bovine blood microthrombi were injected onto the mesh until upstream pressure was 30 mmHg. US was delivered for 20 min (1 MHz, 1.5 MPa peak negative pressure, 3 sec pulse interval, 1000-5000 cycles) with and without low dose tPa (2.5 μg/ml) during measurement of upstream pressure to assess SRP efficacy (n = 3-7). Lytic rate (rate of pressure drop in the first 4 min) and lytic index (1/area under pressure-time curve) quantified SRP efficacy.

Results:
In whole blood, lytic rate was 2.6 ± 1.5 mmHg/min at 1000 cycles US+MB increasing to 7.3 ± 3.2 mmHg/min at 5000 cycles US+MB (p<0.01) without tPa. The lytic index was similar for tPa only (2.0 ± 0.5) x 10
-3
mmHg
-1
.min
-1
and 5000 cycles US + MB without tPa (2.3 ± 0.5) x 10
-3
mmHg
-1
.min
-1
(p=0.5) but increased to (3.6 ± 0.8) x 10
-3
mmHg
-1
.min
-1
(p<0.01) for 5000 cycles US+MB+tPa, indicating an additive effect of tPa with US + MB therapy (Fig 1).

Conclusions:
In whole blood, US + MB therapy restored microvascular perfusion. Similarly to our previous findings with PBS perfusate, SRP efficacy varied with cycle length in the presence of MB. The addition of tPa increased SRP efficacy in blood, suggesting a potential additive effect of low dose tPa and US + MB therapy
in vivo
.
Abstract 11328: Plasma Chemerin is a Strong and Independent Predictor of Cardiovacular Event Risk
Authors: Leiherer Andreas , Muendlein Axel , Rein Philipp , Geiger Kathrin , Fraunberger Peter , Vonbank Alexander , Saely Christoph H , Drexel Heinz
Published: July 2021

Introduction:
Associations of the adipokine chemerin with the metabolic syndrome (MetS) and with chronic kidney disease (CKD), two important indicators of increased cardiovascular event risk, have been described. However, the power of chemerin to predict cardiovascular events has not been investigated so far and is addressed in the present study.

Hypothesis:
We hypothesized that high plasma chemerin is associated with an increased cardiovascular event risk.

Methods:
We measured plasma chemerin in a high-risk cohort of 495 patients undergoing coronary angiography for the evaluation of suspected or established coronary artery disease (CAD) in which cardiovascular events were prospectively recorded over 3.5±1.1 years. Significant baseline CAD was diagnosed in the presence of coronary artery stenoses ≥50%.

Results:
At baseline, plasma chemerin was significantly higher in patients with the MetS as defined by the current harmonized consensus definition (n=147) than in non-MetS subjects (201±71 ng/ml vs. 163±62 ng/ml p<0.001) and was inversely correlated with estimated glomerular filtration rate (eGFR; r=-0.33, p<0.001). During follow-up, chemerin significantly predicted cardiovascular events (n=82) univariately, after adjustment for age, gender, BMI, and eGFR, and also after additional adjustment for the presence of significant baseline CAD, with standardized hazard ratios of 1.83 [1.19-2.83], p= 0.006; 1.77 [1.12-2.80], p =0.015; and 1.69 [1.07-2.67], p=0.024, respectively.

Conclusions:
From this first prospective evaluation of the cardiovascular event risk associated with chemerin we conclude that chemerin is strongly predictive of cardiovascular events independently from standard risk factors, from the MetS, and from the baseline presence of CAD.
Abstract 11474: Deficiency of Senescence Marker Protein-30 Impairs Collateral Growth by Supressing Nitric Oxide Bioactivity Under Ischemia
Authors: Yamauchi Hiroyuki , Saitoh Shu-ichi , Owada Takashi , Takeishi Yasuchika
Published: July 2021

Aging impairs collateral growth under ischemia and reduces the expression of VEGF, however the exact mechanism is unclear. Senescence marker protein-30 (SMP30) decreases with aging. Mice with SMP30 deficiency, a model of aging, have a short lifespan with increased oxidant stress. To elucidate the effect of SMP30 on ischemia-induced collateral growth, we examined the recovery of cutaneous blood flow (CBF) after femoral artery ligation by laser Doppler imaging in mice. Recoveries of CBF and tissue capillary density were suppressed in SMP30 knockout (KO) mice compared to those of wild type (WT) mice (Figure). Acetylcholine (ACh, 1 μM)-induced NO generation, total thiol and reduced glutathione (GSH) levels in aorta of SMP30 KO mice were lower than those of WT mice (NO: 2.6±4.5 vs. 86.2±9.2 nM; total thiol: 6.3±1.6 vs. 33.2±4.6 nmol/mg/protein; GSH: 5.1±0.8 vs. 18.6±2.1 nmol/mg/protein; P<0.01, respectively). Superoxide generation and NADPH oxidase activity were greater in aorta of SMP30 KO mice compared to that of WT mice (superoxide level: 3.3±0.5 vs. 1.6±0.2 nmol/mg protein; NADPH oxidase activity: 3240±254 vs. 982±106 RLU; P<0.01, respectively). Asymmetric dimethylarginine (ADMA) level was higher in aorta of SMP30 KO mice than that of WT mice (6.4±0.8 vs. 2.4±0.4 nmol/mg protein, P<0.01). VEGF content in the crural muscle in SMP30 KO mice did not increase in 14 days post-ischemia compared to that in pre-ischemia (SMP30 KO mice 1.1±0.2 fold vs. WT mice 2.2±0.3 fold, P<0.01). Akt phosphorylation in the crural muscle was attenuated in SMP30 KO mice compared to that of WT mice (p-Akt/Akt: SMP30 KO mice 0.4±0.3 vs. WT mice 1.2±0.4, P<0.01). Thus, SMP30 deficiency exacerbates oxidant stress due to NADPH oxidase activation, which leads to the rarefaction of collateral growth induced by ischemia related to Akt-VEGF pathway. These results suggest that the decrease of SMP30 in aging impairs VEGF/NO-dependent angiogenesis associated with overproduction of superoxide.
Abstract 11486: Velocity of the Heart Vector Through the QRS Complex Predicts Sudden Cardiac Death in Cardiovascular Disease-Free Adults
Authors: Tereshchenko Larisa G , Henrikson Charles A , Soliman Elsayed , Kabir Muammar , Agarwal Sunil , Sotoodehnia Nona , Siscovick David S , Arking Dan , Solomon Scott , Post Wendy , Coresh Josef , Josephson Mark E
Published: July 2021

Introduction:
The majority of sudden cardiac deaths (SCDs) occur due to ventricular arrhythmia as the first manifestation of the coronary heart disease (CHD) in the general population.

Hypothesis:
We hypothesized that velocity of heart vector movement through the QRS is associated with SCD.

Methods:
A community dwelling cohort was studied. We excluded participants with paced rhythm, atrial fibrillation, prevalent CHD, heart failure, and QRS duration ≥120 ms; remaining participants (n = 13, 368, mean age 53.9±5.7ms; 56.5% female; 73.2% white) were analyzed. Baseline resting 12-lead ECG was transformed into orthogonal XYZ; filtered (40-49Hz) QRS loop length was measured. Velocity was calculated as the distance traveled by filtered heart vector over each 10ms of QRS length, divided by time.

Results:
During a median follow up of 14 years, 183 participants had SCD. Averaged baseline conduction velocity (9.3±3.9 vs. 7.7±3.6 μV/ms; P=0.0001) and conduction over 110-119ms of QRS (2.6±1.3 vs. 2.1±0.9; P<0.0001) was faster in those who had SCD than those without. In unadjusted Cox regression velocity at 110-119ms (continuous variable HR 1.42; 95% CI 1.29-1.57) and velocity at 100-109ms (HR1.14; 95%CI 1.07-1.21) were associated with SCD (Figure 1). After adjustment for age, sex, CHD risk factors (total cholesterol, triglycerides, high density lipoprotein, current smoking, diabetes, body mass index, leisure activity index, systolic blood pressure, use of antihypertensive drugs), QT-prolonging drugs, ECG characteristics (heart rate, QRS duration, QTc, QRS-T angle, sex-specific Cornell product), and stratified by race and study center, 110-119ms velocity (HR 1.21; 95%CI 1.08-1.36) and 100-109ms velocity (HR 1.09; 95%CI 1.02-1.16) remained significant predictors of SCD.

Conclusions:
Increased velocity of the heart vector movement through terminal 20 ms of filtered QRS loop is an independently associated with SCD in community-dwelling cohort of CHD-free adults.
Abstract 115: Video Review and Time-Motion Analysis of the Causes of No-Flow Intervals as Recorded by Accelerometer During Cardiopulmonary Resuscitation
Authors: Lee Yi-Chia , Yeh Huang-Fu , Chen Yen-Pin , Chang Chun-Yi , Chen Wei-Ting , Chou Eric Hao-Chang , Chong Kah-Meng , Wang Hui-Chih , Chang Anna Marie , Ko Patrick Chow-In , Chiang Wen-Chu , Ma Matthew Huei-Ming
Published: July 2021

Objectives:
Accelerometer (Q-CPR) has been developed and promoted to monitor the quality of cardiopulmonary resuscitation (CPR). Although the device registers the occurrence of no-flow intervals, it does not provide comprehensive information on the causes leading to these no-flow intervals. This study is aimed to analyze causes leading to CPR interruptions registered by Q-CPR by reviewing corresponding video recordings of the resuscitation sessions.

Methods:
Accelerometer recordings (Q-CPR, Philips) of 20 CPR episodes from December 2010 to April 2014 in a tertiary university ED were obtained. Frequency, timing, duration, and types of no-flow intervals, defined as no-flow duration >= 1.5 seconds, were reviewed. Video recordings of the corresponding CPR sessions were reviewed. Causes leading no flow intervals registered by Q-CPR were categorized and analyzed.

Results:
The duration of CPR reviewed for the cases averaged 8.59 minutes (range 2.23 - 19.04 minutes). No-flow intervals (pauses >= 1.5 seconds) occurred 122 times (averaged one interruption every 1.27 minutes of CPR) with an average no-flow intervals of 6.45 seconds (range 1.54 - 51.50 seconds). Through detail review of the video-recordings corresponding to the no-flow intervals registered by Q-CPR, the leading causes of no-flow intervals are associated with pulse checks for pulseless electric activity- PEA (19.5%), pre-shock pauses (13.9%), ultrasound exam (11.6%) and intubation (9.6%), as displayed in the following chart.

Conclusion:
Video recording and time-motion analysis provide detailed information on the causes leading to no-flow intervals registered by QCPR, and could complement information acquired by Q-CPR. Measures should be taken to address leading causes of CPR interruption, especially pulse checks for PEA and pre-shock pauses, to promote quality of CPR.
Abstract 11500: J-Point Syndromes From the Vectorcardiogram Point of View
Authors: Pastore Carlos A , Samesima Nelson , Pereira Horácio G
Published: July 2021

Introduction:
The potentially fatal outcome related to J-point syndromes raises heated debate about the pathophysiology of Brugada syndrome (BrS) and early repolarization (ER). It has not been established yet if they carry a depolarization, a repolarization or both electrical problems.

Hypothesis:
The objective of this study was to define BrS and ER characteristic and distinctive electrical patterns, using aspects of the QRS complex loops, ST-segments and T-waves obtained from the classical vectorcardiogram (VCG).

Methods:
VCG loops of 29 BrS patients and 30 individuals with ER were analyzed qualitatively and quantitatively. Non-paired t-test and ROC curve statistics were used (p≤ 0.05 significance level).

Results:
Mean age: 47±15 vs 38±14y.o. (p=0.02), 66% vs 90% male (p=0.03); QRS duration: 102±10 vs 95±13ms (p=0.03), BrS vs ER, respectively. All QRS loops showed an end-conduction delay located in right posterior-anterior quadrant (BrS) or left posterior-anterior quadrant (ER). A “break” in the QRS loop end, very much resembling a “nose”, is seen in BrS (100%), while in ER the QRS loop “break” was smoother with a “fish-hook” shape (100%). Normal T-wave loops with counterclockwise rotation were present in 86.2% of BrS and 73.3% of ER. End-conduction delay of 34±6ms vs 22±5ms (p<0.0001); J-point amplitude of 0.14±0.07mV vs 0.22±0.08mV (p<0.0001); SÂJ-point of 103±19° vs 55±16° (p<0.0001), BrS vs ER, respectively. A 75o cutoff value (ROC analysis) could diagnose BrS (96.6% sensitivity, 93.3% specificity).

Conclusions:
The vectorcardiogram could clearly differentiate BrS from ER qualitatively as well as quantitatively: the transverse plane of VCG shows in BrS cases a longer end-conduction delay (>30ms), with a right-sided and posterior-anteriorly oriented loop, with the aspect of a “nose”; in ER cases the end-conduction delay is shorter, located at the left posterior-anterior quadrant, with the aspect of a “fish-hook”. With a J-point angle above 75o we could diagnose BrS with 96.6% sensitivity and 93.3% specificity.
Abstract 11505: Arterial Inflammation in HIV-Infected Patients Assessed by 18F-Fluorodeoxyglucose Positron Emission Tomography
Authors: Ripa Rasmus S , Knudsen Andreas , Hag Anne Mette F , Loft Annika , von Benzon Eric , Keller Sune H , Møller Holger J , Lebech Anne-Mette , Kjær Andreas
Published: July 2021

Introduction:
HIV-infected patients are at increased risk of myocardial infarction and arterial inflammation has been suggested as an explanation. Vascular inflammation can be assessed in vivo by 18F-fluorodeoxyglucose (FDG) PET.

Hypothesis:
Well-treated HIV-infected patients without known cardiovascular disease will have increased uptake of FDG in different arterial regions as compared to healthy controls.

Methods:
We prospectively included 26 HIV-infected patients on stable antiretroviral therapy and 25 healthy volunteers. All underwent whole-body PET/CT 3 hours after injection of FDG. FDG uptake was assessed (SUV) in the carotid arteries, the ascending, descending, and abdominal aorta. Carotid intima-media thickness was determined by ultrasound. Soluble biomarkers of endothelial dysfunction and inflammation were measured by ELISA. Known cardiovascular risk factors were recorded for all included.

Results:
The HIV-infected patients were on stable antiretroviral therapy with full viral suppression. The HIV-infected group was older (50 vs 41 yrs; p = 0.01), had higher blood pressure and total cholesterol, and accordingly a higher Framingham risk score. FDG uptake was similar in the two groups quantified as SUVmax (figure) in the carotid region (1.67 ± 0.04 vs. 1.67 ± 0.04, p = 0.98), the ascending aorta (1.84 ± 0.06 vs. 1.97 ± 0.06, p = 0.15), the descending aorta (1.89 ± 0.08 vs. 1.93 ± 0.08, p = 0.70), and the abdominal aorta (1.70 ± 0.06 vs. 1.65 ± 0.06, p = 0.56) even when adjusting for differences in risk profile. No significant correlations between SUV, carotid intima-media thickness, known cardiovascular risk factors and soluble biomarkers were found.

Conclusions:
We found no evidence of increased arterial inflammation among HIV-infected patients with full viral suppression compared to controls. This may challenge the idea of chronic inflammation as the cause of cardiovascular disease among optimally treated HIV-infected patients.
Abstract 11558: Sitagliptin Attenuated Brain Damage and Cognitive Impairment in Mice With Chronic Cerebral Hypo-Perfusion Through Suppressing Oxidative Stress and Inflammatory Reaction
Authors: Tsai Tzu -Hsien , Chua Sarah , Sheu Jiunn-Jye , Leu Steve , Yip Hon Kan
Published: July 2021

Background:
Sitagliptin, a new anti-diabetic drug that inhibits dipeptidyl peptidase (DPP)-4 enzyme activity, has been reported to possess neuroprotective property. We tested the protective effect of sitagliptin against chronic cerebral hypoperfusion (CHP) in mice after bilateral carotid artery stenosis (BCAS).

Methods:
Thirty C57BL/6 mice were divided into three groups: Sham control (SC) (n=10), CHP (n=10), CHP-sitagliptin (orally 600mg/kg/day) (n=10). Working memory was assessed with novel-object recognition test. Magnetic resonance imaging (MRI) was performed at day 0 and day 90 after BCAS procedure prior to sacrifice.

Results:
Immunohistochemical (IHC) staining showed significantly enhanced microglia activation, astrocytosis, and demyelinating change of white matter in CHP group than in SC but the changes were significantly suppressed after sitagliptin treatment (all p<0.01). The mRNA expressions of inflammatory (TNF-α, MCP-1and MMP-2) and apoptotic (Bax) biomarkers showed an identical pattern, whereas the anti-inflammatory (IL-10) and anti-apoptotic (Bcl-2) biomarkers showed an opposite pattern compared to that of IHC among all groups (all p<0.01). The protein expressions of oxidative stress (NOX-I, NOX-II, nitrotyrosin, oxidized protein), inflammatory (NF-κB, TNF-α and MMP-2), apoptotic (mitochondrial Bax, cleaved PARP), and DNA-damage (γ-H2AX) markers showed an identical pattern, while expression pattern of anti-apoptotic marker (Bcl-2) was opposite to that of IHC (all p<0.01). Glycogen-like peptide-1 receptor protein expression progressively increased from SC to CHP-sitagliptin (p<0.01). The short-term working-memory loss and cortical-matter reduction on MRI-T2 showed a pattern identical to that of IHC in all groups (all p<0.01).

Conclusion:
Sitagliptin protected against cognitive impairment and brain damage in a murine CHP model.

Key words:
chronic cerebral hypoperfusion, sitagliptin, oxidative stress inflammation
Abstract 11585: Is Brachial Flow-Mediated Dilation the Predictor of Development of Cardiac Allograft Vasculopathy in Recipients With Heart Transplantation?
Authors: Watanabe Takuya , Seguchi Osamu , Nishimura Kunihiro , Yanase Masanobu , Sato Takuma , Sunami Haruki , Nakajima Seiko , Hisamatsu Eriko , Sato Takamasa , Kuroda Kensuke , Nakao Yoko , Nakai Michikazu , Takegami Misa , Hata Hiroki , Fujita Tomoyuki , Miyamoto Yoshihiro , Nakatani Takeshi , Kobayashi Takashi , Higashiyama Aya , Watanabe Makoto , Kokubo Yoshihiro
Published: July 2021

Introduction:
Cardiac allograft vasculopathy (CAV) is one of the main causes of death in heart transplant (HTx) recipients. Usefulness of FMD for predictor of CAV progression is not clear.

Methods:
Forty three HTx recipients were included and they underwent measurement of FMD at mean 4.8 years after HTx. All recipients were performed three-dimensional intravascular ultrasounds (3D-IVUS) analysis just after HTx (First; mean 0.3 ± 0.5 year after HTx) and at the time (Last; mean 4.8 ± 3.7 year after HTx) when FMD was performed. We defined the impairment of endothelial function (I-EF) as brachial artery FMD<6.0%. The median of plaque volume index (PVI, plaque volume/measured vessel length) at first IVUS was 0.92 mm
3
/mm. The subjects were sub classified according to PVI at first IVUS, the greater PVI group (≧0.92 mm
3
/mm) and the less PVI group (<0.92 mm
3
/mm).

Results:
Most of HTx recipients were diagnosed as non-ischemic heart disease (95.3%). 16 recipients had impairment of endothelial function (I-EF group). At first and last IVUS, PVI were significantly greater in the I-EF group. Endothelial function was significantly impaired in 10 recipients (45.5%) in the greater PVI group and 6 (28.6%) in the less PVI group. In the greater PVI group, recipients with I-EF had a greater PVI at last IVUS in the comparison with recipients without I-EF (2.23±0.89 vs 3.87±1.84 mm3/mm, p=0.013). In the less PVI group, there were no significant difference in PVI at last IVUS between with and without I-EF (0.81±0.49 vs 1.50±1.25 mm3/mm/year, p=0.075). After multivariate adjustment for the greater PVI(≧0.92 mm
3
/mm) at baseline, time of last IVUS year since HTx and the presence of I-EF, the presence of I-EF was independently associated with PVI at last IVUS (β coefficient=1.16, 95%CI; 0.42 to 1.90, p=0.003).

Conclusions:
Impairment of endothelial function was associated with the plaque progression in HTx recipients.
Abstract 11653: Prognostic Value of Combination of Flow-Mediated Vasodilation and Nitroglycerine-Induced Vasodilation
Authors: Kajikawa Masato , Higashi Yukihito , Maruhashi Tatsuya , Iwamoto Yumiko , Matsumoto Takeshi , Iwamoto Akimichi , Oda Nozomu , Hidaka Takayuki , Nakashima Ayumu , Noma Kensuke , Kihara Yasuki
Published: July 2021

Introduction:
Flow-mediated vasodilation (FMD) as an index of endothelium-dependent vasodilation and nitroglycerine-induced vasodilation as an index of endothelium-independent vasodilation in the brachial artery using high-resolution ultrasound are useful for assessing vascular function. Some studies have shown that endothelial function assessed by FMD can serve as an independent predictor of cardiovascular events. Previously, we reported that nitroglycerine-induced vasodilationcan be used as a marker for identifying patients with advanced atherosclerosis. The purpose of this study was to determine the prognostic impact of cardiovascular events between FMD and FMD combined with nitroglycerine-induced vasodilation.

Methods and Results:
We measured FMD and nitroglycerine-induced vasodilation in 402 subjects (mean age, 58±17 years), including patients with cardiovascular diseases. We assessed the associations between FMD combined with nitroglycerine-induced vasodilation and cardiovascular events (death from cardiovascular causes, myocardial infarction, stroke, and revascularization). During a median period of 32.3 months (interquartile range, 17.1 to 49.1 months) of follow-up, 15 subjects died (5 from cardiovascular causes), 3 myocardial infarction, 7 stroke, and 26 revascularization. The receiver operating characteristic curve analysis revealed that FMD alone predicts cardiovascular events with an area under curve of 0.67. FMD combined with nitroglycerine-induced vasodilation predicts cardiovascular events with an area under curve of 0.70. FMD < median value of 3.9% and nitroglycerine-induced vasodilation < median value of 12.2% were associated with increased cardiovascular event. After adjustment for age, sex, body mass index, cardiovascular risk factors, below median FMD and nitroglycerine-induced vasodilation group remained a strong independent indicator of cardiovascular events (hazard ratio, 4.95; 95 percent confidence interval, 1.65 to 21.43; P=0.002).

Conclusions:
These findings suggest that the combination of FMD and nitroglycerine-induced vasodilation measurement could more accurately predict cardiovascular events than FMD alone.
Abstract 11656: Ranolazine Improves Cardiovascular-and Diabetes-Related Healthcare Utilization in Patients With Chronic Stable Angina and Co-Morbid Diabetes
Authors: Page Robert L , Ghushchyan Vahram , Allen Richard A , Hartsfield Cynthia L , Koch Bruce R , Nair Kavita V
Published: July 2021

Introduction:
Ranolazine(RAN) may improve cardiovascular (CV) and diabetes (DM) healthcare utilization and outcomes in patients with chronic stable angina (CSA) and DM.

Methods:
Medical, pharmacy claims linked with laboratory data from 2008-2012 were analyzed using a commercial database. Patients with CSA receiving RAN, beta blocker (BB),calcium channel blocker (CCB), or long-acting nitrate (nitrate), along with sublingual nitroglycerin were identified and followed for 12 months after antianginal therapy change. Therapy change was defined as adding or switching to another antianginal or RAN (index date) following previous therapy. Four CSA groups were identified (BB, CCB, nitrates,RAN) and propensity matched based on baseline age, gender, chronic condition index, ACS, hypertension, DM, heart failure, hyperlipidemia, DM related complications, and CV costs. A subset of patients with DM represented the study groups. Logistic regression models were developed comparing revascularization at 30, 60, 90, 180 and 360 days between groups. Negative binomial regression was used to compare CV and DM related healthcare utilization. Descriptive differences in HbA1C levels pre and post therapy change were reported.

Results:
3724 patients were identified (BB, n=933;CCB,n=940; nitrates,n=937, RAN, n=914). Majority (61-65%) were male with a mean age of 66-67 years. Compared to other antianginals, RAN exhibited significantly lower odds for revascularization at all time periods, a lower rate for CV related outpatient and ER visits, and a reduced expected rate of DM related inpatient length of stay (Table). RAN was associated with a mean HbA1C reduction of 0.20 mg/dl compared to the BB (0.14 mg/dl increase, p=0.028), CCB (0.21 mg/dl increase, p=0.005), and nitrate (0.05 mg/dl decrease, p=0.277) cohorts.

Conclusion:
RAN demonstrated lower CV and DM healthcare utilization compared to traditional antianginals, while not worsening glycemic control vs. BB and CCB.
Abstract 11678: Mitochondrial Reactive Oxygen Species Mediate Lysophosphatidylcholine-Induced Endothelial Cell Activation
Authors: Li Xinyuan , Fang Pu , Li Ya-Feng , Kuo Yin-Ming , Andrews Andrew J , Koch Walter J , Wang Hong , Yang Xiao-Feng
Published: July 2021

Background:
Lysophosphatidylcholines (LPCs) are a class of pro-inflammatory lipids that play important roles in atherogenesis. LPC activates endothelial cells (ECs) to upregulate adhesion molecules and chemokines, which is the initiation step of atherogenesis. However, the mechanisms underlying LPC-triggered EC activation are not fully understood. Previously considered as the toxic by-products of cellular metabolism, mitochondrial ROS (mtROS) are recently found to directly contribute to both the innate and adaptive immune responses. Here we tested a novel hypothesis that mtROS serve as signaling mediators for LPC-induced EC activation.

Methods and Results:
Using electron spin resonance and flow cytometry with fluorescence probe MitoSOX, we found that several LPC species including LPC 16:0, 18:0, and 18:1 induced mtROS in human primary aortic ECs (HAECs). Mechanistically, our analysis using mitochondrial calcium inhibitor and Seahorse XF96 mitochondrial function analyzer showed that LPC induced mtROS via increasing mitochondrial calcium entry which resulted in mitochondrial proton leakage. In addition, we found that mtROS scavenger MitoTEMPO abolished LPC-induced EC activation by downregulating Intercellular adhesion molecule 1 (ICAM-1) and Vascular cell adhesion protein 1 (VCAM-1) in HAECs. Moreover, our analysis with transcription factor profiling screening showed that MitoTEMPO acts by blocking LPC-induced nuclear translocation of pro-inflammatory transcription factor activator protein-1 (AP-1).

Conclusions:
Our results indicate that mtROS are responsible for LPC-induced EC activation and that mtROS may serve as a novel therapeutic target for vascular inflammation.
Abstract 11683: Recurrence of Atrial Arrhythmias Following Ablation in Adults With Congenital Heart Disease: New Substrate Formation or Late Procedural Failure?
Authors: Shuplock Jacqueline , Barker Gregory , Radbill Andrew , Kannankeril Prince , Fish Frank A
Published: July 2021

Introduction:
Using current mapping and ablation tools, high acute success rates can be achieved in repaired adult congenital heart disease (CHD) patients with atrial arrhythmias, but recurrences are common. We examined the nature of recurrence in a cohort of repaired adult CHD patients.

Hypothesis:
We tested the hypothesis that recurrences after ablation in repaired CHD patients represent the development of new substrates.

Methods:
A retrospective chart review was performed on all repaired adult CHD patients undergoing ablation for atrial arrhythmias, excluding atrial fibrillation (AF), at our institution from Jan. 2003-Nov. 2013. CHD lesions were grouped as tetralogy-type, atrial switch, single ventricle, and other. Latest follow-up data were obtained on all patients. Acute procedural success was defined as ablation of all targeted circuits. All recurrences warranting clinical intervention were noted.

Results:
A total of 118 patients underwent 157 ablation procedures, and 253 tachycardias were targeted. Of these, 99 utilized the cavo-tricuspid isthmus (CTI), 88 were non-isthmus-dependent scar-related macro-reentry, 55 were focal tachycardias, and 13 were atrioventricular reciprocating tachycardias. Acute procedural success was obtained in 147/157 (94%) procedures and 237/253 (94%) targeted arrhythmias. Recurrence was observed after 78 (50%) procedures after a median time of 6 months. Of those undergoing repeat ablations, new substrates were found to be the cause of recurrence in 18 (23%), while recurrence of the original substrate was documented in 20 (26%). AF accounted for 9 (12%) of the recurrences. By lesion type, recurrence was most common among single ventricle patients (81% vs. all others 42%, p <0.001).By substrate, recurrence was lowest with CTI-dependent circuits (35% vs. all others 56%, p=0.016).

Conclusions:
Despite high acute procedural success rates, patients with repaired CHD had frequent recurrence of atrial arrhythmias. These represented both new substrates, including the development of AF, and recurrence of previously-ablated substrates with a similar frequency. Repeat ablation may be warranted in those with recurrences as a new target for ablation may be identified.
Abstract 11733: Assessment of Carotid Plaque Neovascularization Using Quantitative Analysis of Contrast-Enhanced Ultrasound Imaging is Useful for Risk Stratification in Patients With Coronary Artery Disease
Authors: Nakamura Jun , Nakamura Takamitsu , Deyama Juntaro , Fujioka Daisuke , Kawabata Ken-ichi , Obata Jun-ei , Watanabe Kazuhiro , Watanabe Yosuke , Kugiyama Kiyotaka
Published: July 2021

Introduction:
Extensive neovascularization in atherosclerotic plaque has been shown to be associated with plaque progression and instability, leading to atherosclerotic cardiovascular events. Contrast-enhanced ultrasound (CEUS) of the carotid artery is a potential technique for imaging plaque neovascularization.

Hypothesis:
Assessment of intra-plaque neovascularization of the carotid artery using quantitative analysis of CEUS provides prognostic information in patients with coronary artery disease (CAD).

Methods:
This study included 206 patients with stable CAD and with carotid intima-media thickness (IMT) > 1.1 mm. They underwent a CEUS examination of the carotid artery and were followed-up prospectively for < 38 months or until a cardiac event (cardiac death, non-fatal myocardial infarction [MI], unstable angina pectoris [uAP] requiring unplanned coronary revascularization, or heart failure requiring hospitalization). The degree of contrast signals measured within the carotid plaque after the intravenous injection of contrast material was quantified by calculating the increase in mean gray scale level within the region of interest of the carotid plaque, expressed as plaque enhanced intensity.

Results:
During the follow-up period (3 - 38 months, mean 22.8 ± 11.8 months), 31 events occurred (2 cardiac deaths, 7 non-fatal MIs, 16 uAP, and 6 heart failure). Multivariate Cox proportional hazards analysis showed that plaque enhanced intensity was a significant predictor of cardiac events independent of traditional risk factors (HR, 1.52; 95% CI, 1.20 - 1.94; p = 0.001). The addition of plaque enhanced intensity had a significant incremental effect on the area under the ROC curve (AUC) generated using baseline model of traditional risk factors (AUC: baseline model 0.69 vs. baseline model + plaque enhanced intensity 0.78, p = 0.03). The addition of the plaque enhanced intensity to the baseline risk factors resulted in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.58, p = 0.003; and IDI 0.078, p = 0.03).

Conclusions:
The assessment of carotid plaque neovascularization using quantitative analysis of CEUS may be useful for risk stratification in patients with CAD.
Abstract 11798: The Usefulness of Combined Assessment of E/e’ Ratio and Transmitral Flow Pattern to Interpret Cardiac Condition
Authors: Oikawa Masayoshi , Kobayashi Atsushi , Yamauchi Hiroyuki , Suzuki Satoshi , Yoshihisa Akiomi , Nakazato Kazuhiko , Suzuki Hitoshi , Saitoh Shu-ichi , Takeishi Yasuchika
Published: July 2021

Background:
High mitral inflow E velocity to tissue Doppler e’ ratio (E/e’) is implicated as increased left ventricular (LV) filling pressure, but it is not always consistent with clinical findings. Early (E) and late (A) diastolic filling velocity ratio (E/A) is also used to evaluate LV diastolic function and filling pressure, but the usefulness of combined assessment of E/e’ and E/A is not fully understood.

Methods:
We retrospectively analyzed 1266 patients who underwent echocardiography to assess cardiac function between January 2013 to March 2014 in our hospital. The patients were grouped based on the values of E/e’ (low E/e’<15, high E/e’≥15) and E/A (low E/A≤0.8, high E/A>0.8).

Results:
First, we analyzed a role of E/A in the setting of high E/e’ condition. The low E/A with high E/e’ group (n=95) displayed lower tricuspid regurgitant pressure gradient (TRPG, 22 [16-28] mmHg vs. 29 [23-38] mmHg, P<0.01) and smaller inferior vena cava (IVC) diameter (12 [10-15] mm vs. 14 [11-17] mm, P<0.01) than the high E/A with high E/e’ group (n=136), suggesting that low E/A indicated controlled fluid retention even with high E/e’. We next investigated the role of E/e’ in the situation of low E/A state. Compared to the low E/A with low E/e’ group (n=584), the low E/A with high E/e’ group showed similar TRPG (22 [16-28] mmHg vs. 21 [17-26] mmHg, ns), similar IVC diameter (12 [10-15] mm vs. 12 [10-15] mm, ns), but larger LV end-diastolic diameter (48 [42-52] mm vs. 45 [40-50] mm, P<0.01), larger left atrial volume (53 [38-67] ml vs. 41 [29-54] ml, P<0.01), lower LV ejection fraction (59 [47-66]% vs. 63 [57-67]%, P<0.01), and slower LV systolic velocity (5.9 [4.9-7.3] cm/s vs. 7.8 [6.5-9.5] cm/s, P<0.01), indicating that high E/e’ was a predictor of LV remodeling and dysfunction in the situation of low E/A condition.

Conclusions:
The low E/A indicated controlled fluid retention regardless of E/e’ value. A high E/e’ reflected LV remodeling and dysfunction. Thus, we conclude that combined assessment of E/e’ and E/A is useful to interpret cardiac condition.
Abstract 11845: Impaired Peripheral Endothelial Function Assessed by Digital Reactive Hyperemia Peripheral Arterial Tonometry and Risk of In-Stent Restenosis
Authors: Komura Naohiro , Tsujita Kenichi , Yamanaga Kenshi , Sakamoto Kenji , Miyazaki Takashi , Tabata Noriaki , Ishii Masanobu , Akasaka Tomonori , Arima Yuichiro , Ono Takamichi , Kojima Sunao , Tayama Shinji , Kaikita Koichi , Sugiyama Seigo , Hokimoto Seiji , Hibi Kiyoshi , Kimura Kazuo , Umemura Satoshi , Ogawa Hisao
Published: July 2021

Introduction:
Drug-eluting stents (DESs) are replacing bare-metal stents (BMSs), but in-stent restenosis (ISR) remains a problem. Impaired endothelial function is a key event in the atherosclerosis process and a predictor of future cardiovascular events. Reactive hyperemia index (RHI) assessed by peripheral arterial tonometry (PAT) evaluates endothelial function noninvasively.

Hypothesis:
We prospectively assessed the prognostic value of RHI in predicting ISR after percutaneous coronary intervention (PCI).

Methods:
RHI was measured using Endo-PAT 2000 before PCI (initial RHI) and at follow-up angiography (F/U RHI) in 249 consecutive patients who had successful PCI. F/U angiography was performed at six and nine months after PCI with BMS and DES, respectively. ISR was defined as percent diameter stenosis >50% at F/U angiography assessed by quantitative coronary angiography.

Results:
At F/U, ISR was seen in 68 patients (27.3%). F/U ln(RHI) was significantly lower in patients with ISR than in those without (0.52 ± 0.23 vs. 0.65 ± 0.27, p < 0.01); no between-group difference in initial ln(RHI) was seen (0.60 ± 0.26 vs. 0.62 ± 0.25, p = 0.56). By multivariate logistic regression analysis, even after adjusting for other significant parameters in univariate analysis (BMS use, total stent length, HDL-Cholesterol, HbA1c, calcium antagonist use, and post-PCI minimum lumen diameter), F/U ln(RHI) independently predicted ISR (odds ratio: 0.13; 95% confidence interval [CI]: 0.04-0.48; p = 0.002). In receiver operating-characteristic analysis, F/U RHI was the strongest predictor of ISR (area under the curve [AUC]: 0.67; 95% CI: 0.60-0.75; p < 0.01; RHI < 1.73 had 67.6% sensitivity, 64.1% specificity); AUC significantly improved from 0.62 to 0.70 when RHI was added to traditional ISR risk factors (diabetes mellitus, total stent length, minimum stent diameter) (p = 0.02). Net reclassification index was significant after addition of RHI (26.5%, p = 0.002).

Conclusions:
To our knowledge, this is the first study indicating that impaired RHI at F/U angiography independently predicts occurrence of ISR. The simple and noninvasive assessment of endothelial function by RH-PAT adds incremental prognostic value to ISR-risk stratification following PCI.
Abstract 11861: Ethnic Differences in the 10-Year Risk of Coronary Heart Disease Among High Risk Individuals in a Large Contemporary Population
Authors: Rana Jamal S , Liu Jennifer , Moffet Howard H , Jaffe Marc , Karter Andrew J
Published: July 2021

Purpose:
To evaluate ethnic differences in CHD risk in high risk patient populations in 4 study cohorts: 1) No diabetes (DM) and no prior CHD 2) DM but no prior CHD, 2) non-DM with prior CHD and 3) DM with prior CHD.

Methods:
1,586,061 members of an integrated health care system, with self reported race/ethnicity of Asians (14.1%), blacks (8.6%), Latinos (12.6%), and whites (64.5%), ages 30- 90 years, were evaluated from 01/01/2002 through 12/31/2011. We specified Cox proportional hazard models and compared the Hazard Ratios (HRs), relative to that of whites, for incident CHD in the 4 study cohorts.

Results:
The median follow up time for this cohort was ten years (10,980,800 person years). Figure shows the age and sex adjusted (squares) hazard ratios (relative to that of whites) for CHD for Blacks, Latinos and Asians, respectively for the 4 study groups. These age and sex-adjusted effect estimates were not altered substantively by further adjustment for smoking, HTN, lipid levels and statin use (figure, circles). However a slightly higher risk (HR of 1.15 95%, CI, 1.05-1.27) was noted among Blacks with prior CHD and no DM. No increase risk was noted in blacks with both DM and CHD.

Conclusions:
In this integrated delivery system with uniform medical care coverage, we observed slightly reduced risk or no difference in risk for Blacks, Asians, and Latinos compared to whites in all 4 risk groups, and observed a greater risk of CHD for Blacks without prior DM but with previously diagnosed CHD. These findings may inform policy development and interventions designed to identify and eliminate disparities.
Abstract 11919: AMP-Activated Protein Kinase Response to Metabolic Stress: A Novel Determinant of Atrial Fibrillation Progression
Authors: Harada Masahide , Qi Xiao- Y , Tadevosyan Artak , Voigt Niels , Karck Matthias , Kamler Markus , Kodama Itsuo , Murohara Toyoaki , Dobrev Dobromir , Nattel Stanley
Published: July 2021

Introduction:
Metabolic stress is observed in clinical and experimental atrial fibrillation (AF). Metabolic stress activates AMP-dependent protein kinase (AMPK) via phosphorylation; activated AMPK produces compensatory changes in the determinants of energy balance. Here, we examined AMPK responses in AF and their role in remodeling responses of atrial Ca
2+
handling and contractility.

Methods:
AMPK and Cav1.2 protein were quantified by immunoblot. Ca
2+
transients (CaTs, Indo1 AM), cell shortening (CS, videometry), L-type Ca
2+
(
I
Ca,L
) and NCX (
I
NCX
) current (patch clamp)

were measured in dog left atrial (LA) cardiomyocytes (CMs) under metabolic stress due to glycolysis inhibition (GI, 10 mM 2-deoxyglucose/10 mM pyruvate).

Results:
In dogs with 1-wk electrically-maintained AF (n=4), the phosphorylation ratio (PhR) of AMPK (indicating activation) increased in LA by 101%* (*p<0.05) vs. controls (n=4). Metabolic stress due to GI in 2 Hz paced LA CMs increased AMPK PhR by 103%* vs. quiescent CMs. In 2 Hz paced cells, the AMPK inhibitor CompC (10 μM) decreased LA CaT and CS by 58%* and 51%* vs. control, but the AMPK activator AICAR (1 mM) restored CaT and CS by 75%* and 53%* vs. CompC alone, supporting AMPK-dependent regulation. CompC decreased
I
Ca,L
and
I
Ca,L
-triggered CaT by 46%* and 37%*. AMPKα protein coimmunoprecipitated with Ca
v
1.2 protein, suggesting that AMPK is physically coupled with the
I
Ca,L
channel α-subunit. CompC also decreased SR Ca
2+
content by 53%* vs. control (
I
NCX
simultaneously measured with caffeine-induced CaT). AMPK PhR was greater by 61%* in paroxysmal AF (pAF, n=7) patient atria vs. sinus rhythm controls (n=10), whereas AMPK PhR was decreased in chronic AF (cAF) patients (n=9) by 27%*, suggesting that the level of AMPK activation may govern the chronicization of AF.

Conclusions:
AF activates AMPK. Under AF-induced metabolic stress, AMPK activation limits AF-promoting abnormalities in LA
I
Ca,L
, Ca
2+
handling and contractility. pAF patients have AMPK activation, protecting them against chronicization, whereas cAF patients have reduced AMPK activation. Thus, the response of AMPK to AF-related metabolic stress might be a crucial determinant of AF chronicization, and AMPK-manipulation may be a novel target to prevent AF progression.
Abstract 11930: Late Right Heart Failure During Continuous-Flow Left Ventricular Assist Device Support Adversely Affects Post-Transplant Outcome
Authors: Takeda Koji , Takayama Hiroo , Kalesan Bindu , Colombo Paolo C , Jorde Ulrich P , Yuzefpolskaya Melana , Mancini Donna M , Naka Yoshifumi
Published: July 2021

Background:
Right heart failure (RHF) is an unresolved issue during continuous-flow left ventricular assist device (LVAD) support. There are scarce data about post-transplant outcomes in patients complicated with late RHF during LVAD support.

Objective:
To assess whether development of late RHF during LVAD support adversely affected post-transplant survival.

Methods:
Between May 2004 and December 2013, 141 patients underwent cardiac transplantation after isolated LVAD support as a bridge to transplant at our center. Late RHF was defined as HF requiring medical interventions >4 weeks after LVAD implantation. During the same study period, 3 patients were bridged to transplant with concurrent right ventricular assist device (RVAD) support.

Results:
The mean age of the study cohort was 54 ± 13 years, 81% were male, and 35% had an ischemic etiology. The mean duration of LVAD support before transplantation was 270 days. Twenty-three patients (16%) developed late RHF during waiting period. Of these, 6 required repeated readmissions due to RHF and 12 were supported with inotropic agents at the time of transplantation. Those patients were more likely to have higher creatinine (1.3 ± 0.67 vs. 1.6 ± 0.86, p = 0.08), higher blood urea nitrogen (23 ± 10 vs. 32 ± 16, p = 0.0019), and lower albumin (4.1 ± 0.47 vs. 3.8 ± 0.59, p = 0.0019) levels at the time of transplantation compared to patients who did not develop RHF. Overall post-transplant survival rate were 87%, 83%, 77% at 1, 3, and 5 years, respectively. The 3-year post-transplant survival was significantly worse in patients who developed late RHF (Figure: 87% vs. 61%, p<0.0001). There were no early and late deaths in patients with RVAD support.

Conclusions:
Patients who develop late RHF during LVAD support have diminished post-transplant survival. The initiation of RVAD support may be warranted to improve renal function and nutrition status for these high-risk patients.