bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P403: Blood Pressure Differences Associated With OMNIHEART-like Lower Sodium Compared With Typical American Higher Sodium Nutrient Profile: INTERMAP USA
Authors: Molitor John , Brown Ian J , Chan Queenie , Papathomas Michail , Liverani Silvia , Molitor NuooTing , Richardson Sylvia , Van Horn Linda , Daviglus Martha L , Stamler Jeremiah , Elliott Paul ,   the INTERMAP Rsch Group
Published: July 2021

Background:
The DASH-Sodium trial demonstrated beneficial effects on blood pressure (BP) of the DASH diet with lower sodium intake, compared to typical American diet with higher sodium. The subsequent OMNIHEART trial reported additional benefits for BP by replacing carbohydrate in the DASH diet with either protein or monounsaturated fats.

Objective:
Assess possible BP benefits of a lower sodium OMNIHEART-like diet in free-living Americans using two statistical methods: a linear OMNIHEART nutrient score, and a Bayesian approach comparing estimated BP levels with an OMNIHEART-like lower sodium nutrient profile (“OMNIHEART”) and with a typical American higher sodium profile (“Control”).

Methods:
Cross-sectional data include four 24-h dietary recalls, two timed 24-h urine collections, eight BP readings for 2,195 individuals ages 40-59 from the International Study on Macro/Micronutrients and Blood Pressure (INTERMAP). An OMNIHEART score (with 9 nutrient targets, based on the protein arm of the trial) was calculated for each participant and regressed on BP. For Bayesian profile regression, participants were assigned to clusters based on similarity of their nutrient profiles; pre-specified OMNIHEART and Control profiles were assigned to clusters. Posterior distributions were obtained for mean BP levels associated with OMNIHEART and Control profiles.

Results:
With adjustment for potential confounders, an OMNIHEART score higher by one point was associated with systolic/diastolic BP differences of 1.0/ 0.5 mmHg (both P<0.001). Mean systolic/diastolic BPs were 111.3/68.4 and 115.2/70.6 mmHg for Bayesian OMNIHEART and Control profiles respectively; controlled for possible confounders, average BP differences were 3.9/ 2.2 mmHg (P(diff≥0) =0.98/0.96). Findings were comparable for men and women, for non-hypertensive participants, and with adjustment for antihypertensive treatment.

Conclusions:
These findings indicate broad generalisability of DASH and OMNIHEART trial results, and support recommendations for reduced sodium OMNIHEART-style diet for prevention/control of population-wide adverse BP levels.
Abstract 11178: Effect of Female Gender on Acute Coronary Syndrome Outcomes in Young Patients
Authors: Salam Amar M , AlHabib Khalid , Almahmeed Wael , Alsheikh-Ali Alawi , Sulaiman Kadhim , Amin Haitham , Al-Motarreb Ahmed , Al-Lawati Jawad , Asaad Nidal , Singh Rajvir , Al-Suwaidi Jassim ,   The Second Gulf Registry of Acute Coronary Events(Gulf RACE-2) Investigators
Published: July 2021

Background:
Recent reports have suggested that there are gender differences in the presentation of young adults with acute coronary syndromes (ACS). How these differences may affect ACS outcomes remains unclear, however. The aim of the current study was to examine the prognostic impact of gender in young adults with ACS in a multicenter multinational ACS registry from the Middle East.

Methods:
For a period of 9 months in 2008 to 2009, 7,930 consecutive patients with ACS were enrolled from 65 hospitals in 6 Middle East countries. A cohort of 3933 patients in the age group 55 years and younger were selected of whom 552 were women (14%). Gender differences in presentation and clinical features were examined. Multivariate analysis of in-hospital and one year mortality was also performed.

Results:
The mean age for women was 46 years and for men 48 years. Women had significantly higher rates of diabetes mellitus (50.4% vs. 30.7%), hypertension (57.4% vs. 34.5%), obesity (32% vs. 17%), dyslipidemia (37.5% vs. 26%) and renal impairment (4.1% vs. 1.2%) whereas men were more likely to be smokers (72.4% vs. 14%) [all P<0.001]. Compared to men, women had an increased in-hospital and 1-year mortality rates (3.6% vs. 2.2%, p=0.04, and 9.7% vs. 6.5%, p=0.02, respectively). In multivariate analysis, female gender was an independent predictor of in-hospital mortality (OR, 1.88 [95%CI, 1.02-3.45]; P=0.04) and one year mortality (OR, 1.82 [95%CI, 1.18-2.78]; P=0.007).

Conclusions:
Our study shows that female gender independently and significantly increases the risk of immediate and long term mortality in young patients with ACS.
Abstract 11389: Presentation Symptoms and Outcomes in Diabetic Patients With Acute Coronary Syndromes: Insights From the Second Gulf Registry of Acute Coronary Events
Authors: Salam Amar M , AlHabib Khalid , Almahmeed Wael , Alsheikh-Ali Alawi , Sulaiman Kadhim , Amin Haitham , Al-Lawati Jawad , Al-Motarreb Ahmed , Asaad Nidal , Singh Rajvir , Al-Suwaidi Jassim ,   The Second Gulf Registry of Acute Coronary Events(Gulf RACE-2) Investigators
Published: July 2021

OBJECTIVES:
It is well recognized that cardiac autonomic neuropathy associated with diabetes mellitus (DM) can cause silent myocardial ischemia, however there is limited research examining how the cardiac symptoms reported by patients with DM presenting with acute coronary syndromes (ACS) can affect the immediate and long term outcomes. The aim of the current study was to examine the prognostic impact of lack of chest pain symptoms in DM patients presenting with ACS and enrolled in a multicenter multinational ACS registry from the Middle East.

METHODS:
For a period of 9 months in 2008 to 2009, 7,930 consecutive patients with ACS were enrolled from 65 hospitals in 6 Middle East countries. A cohort of 3135 patients with DM were selected of whom 2686 (85.7%) presented with chest pain while 449 patients (14.3%) had no chest pain. Clinical features and outcomes were examined and compared among the two groups.

RESULTS:
Diabetic patients without chest pain were 5 years older and had significantly higher rates of hypertension (76.1% vs. 63.2%), prior myocardial infarction (35.9% vs. 24.3%), chronic kidney disease (CKD) (17.1% vs. 5.9%) and had significantly higher GRACE risk scores (55.3% vs. 21.4%) at presentation compared to patients with chest pain [All P <0.001]. Covariates independently associated with lack of chest pain in DM patients were; higher Killip class on presentation (OR, 6.2 [95%CI, 4.80-7.88]), female gender (OR, 1.50 [95%CI, 1.14-1.96]), CKD (OR, 1.8 [95%CI, 1.27-2.61]), tachycardia (OR, 2.50 [95%CI, 1.94-3.19]) and advanced age (OR, 1.03 [95%CI, 1.02-1.04]), [All P =0.001]. DM patients without chest pain had a significantly higher in-hospital and 1-year mortality rates (11.4% vs. 3.8%, P =0.001, and 25.7% vs. 12.2%, P =0.001, respectively). Lack of chest pain was an independent predictor of in-hospital and one year mortality (OR, 3.05 [95%CI, 2.05-4.54], P =0.001, and OR, 2.0 [95%CI, 1.52-2.75], P =0.001, respectively).

CONCLUSIONS:
DM patients with ACS presenting without chest pain are at an increased risk of immediate and long term mortality. Understanding the factors associated with atypical presentations of ACS in patients with DM may help in the earlier detection and more appropriate management of these high risk patients.
Abstract 11572: Hyperuricemia Reflects Heart Failure Severity and Predicts Morbidity and Mortality in Patients After the Fontan Operation
Authors: Ohuchi Hideo , Hayama Yosuke , Negishi Jun , Noritake Kanae , Sasaki Osamu , Tsujii Nobuyuki , Iwasa Toru , Sakaguchi Heima , Miyazaki Aya , Yamada Osamu
Published: July 2021

Background:
Serum uric acid level (UA, mg/dl) not only associates with pathophysiology in adult patients with chronic heart failure but also predicts the cardiac events. However, the clinical significance of UA remains unclear in patients after the Fontan operation.

Purpose:
To clarify clinical significance of hyperuricemia (HUA, UA≥7.0) in Fontan patients.

Methods and Results:
We prospectively measured UA in consecutive 306 Fontan patients (16±8 years) and compared the results with the clinical variables, including hemodynamics, exercise capacity, plasma levels of norepinephrine (NE), brain natriuretic peptide (BNP), and unscheduled hospitalization (USH), including all-cause mortality. The UA was 5.8±1.7 and 70 (23%) patients showed HUA. On multivariate model, high levels of plasma creatinine and NE, use of diuretics, low cardiac index, hypoxia, and hyponatrenia independently associated with HUA (p<0.05-0.001), however BNP level did not correlate with UA (p=0.35). During a follow-up of 49±27 months, 69 USH, including 16 deaths, occurred. In addition to BNP levels, HUA independently predicted USH (hazard ratio [HR]: 2.9, 95% confidence interval [CI]: 1.8-4.6, p<0.0001) and mortality (HR: 3.8, 95%CI: 1.4-10, p<0.01). When compared with Fontan patients with normal UA with low BNP, those with HUA and high BNP (≥18.4 pg/ml) had a high HR of 7.0 (CI:3.5-14.1, p<0.0001) and 11.7 (CI:2.9-78.1, p<0.001) for USH and all-cause mortality, respectively.

Conclusions:
UA is a simple and clinically useful marker for stratifying heart failure severity of Fontan patients and HUA predicts the morbidity and mortality.
Abstract 11636: Right Ventricle Lymphatic Vessel Insufficiency Contributes to Interstitial Fluid Stasis, Inflammation, Fibrosis, and Failure in Pulmonary Hypertension
Authors: Colvin Kelley L , Lohani Ozus , Williams Sarah M , Ivy D D , Stenmark Kurt R , Yeager Michael E
Published: July 2021

Introduction:
Pulmonary hypertension (PH) is characterized by cardiopulmonary remodeling. The ensuing right ventricular (RV) hypertrophy and failure contribute to significant mortality. Pericardial effusion worsens the prognosis for PH patients, yet no mechanistic data are available.

Hypothesis:
We hypothesized that lymphatic vessels in rat models of PH would be decreased and dysfunctional compared to controls.

Methods:
We used the Sugen 5416-hypoxia (Su-Hx) and monocrotaline (MCT) models of PH. To assess the degree of cardiac lymphatic vascularity, identify cell types, and to evaluate cell junction complexes in PH rats vs. controls, we used flow cytomtery, qPCR, immunofluorescence, and immunoblot. To assess myocardial edema, we used wet-to-dry weight ratios, echocardiography, and magnetic resonance imaging (MRI). In patients, we used echocardiography and magnetic resonance imaging to quantify RV edema and pericardial effusion.

Results:
We found that the presence of pericardial effusion by either MRI or echocardiography correlated with lower cardiac output in patients with PH (n =6). We found decreased lymphatics in RVs of rats with PH due to either Su-Hx or MCT, compared to controls (n= 5 per group). In the heart, AQP-1+/vWF-/KDR- lymphatic vessels co-expressed podoplanin and were distributed throughout the RV in controls and much less so in PH rats. Lymphatics appeared unchanged in size or number in the left ventricle of all rats. We found increases in myocardial fluid in RVs of PH rats vs. controls, which correlated positively with fibrosis and negatively to cardiac output. The presence of excess myocardial fluid coincided with collagen deposition but without increases in CD68, CD11b, CD11c, or CD163 macrophage infiltration. We observed disturbed connexin-43 and claudin-5 junctional complexes around alpha-actinin+ myocytes and TCF21+ cardiac fibroblasts in PH RVs compared to controls.

Conclusions:
In severe PH, RV function is likely impaired by insufficient lymphatic-mediated fluid clearance and the presence of dysfunctional cell junctions. A clearer understanding of how the cardiac lymphatic system impacts the pathobiology of PH may lead to novel therapy.
Abstract 11983: Auraptene, a Coumaric Compounds Analogous, Improved the Worsening of Systolic Function by Activating Mitochondrial Function After Myocardial Infarction in Rats
Authors: Sunagawa Yoichi , Suzuki Miho , Funamoto Masafumi , Katanasaka Yasufumi , Suzuki Hidetoshi , Murakami Akira , Wada Hiromichi , Imaizumi Atsushi , Hashimoto Tadashi , Shimatsu Akira , Kimura Takeshi , Fujita Masatoshi , Hasegawa Koji , Morimoto Tatsuya
Published: July 2021

Introduction:
Heart failure is associated with pathological growth and mitochondrial dysfunction of constituent cardiomyocytes. To achieve effective oral pharmacological therapy for heart failure, we screened compounds isolated from natural products and found that auraptene derived from the peel of Citrus Hassaku may be applicable to pharmacological therapy for heart failure.

Hypothesis:
We assessed the hypothesis that auraptene could improve the deterioration of mitochondrial function and the development of heart failure in rats with myocardial infarction (MI).

Methods and Results:
In cultured cardiomyocytes, auraptene (2.5-10 μM) dose-dependently repressed phenylephrine-induced hypertrophic responses such as increase in cell size and ANF and ET-1 promoter activations. Auraptene also activated mitochondrial- and lipid metabolism-related gene transcriptions, such as PGC1α, PPARα/γ, mCPT1, UCP3, and PDK4. One week after operation, 22 rats with a moderate size of MI (Fractional shortening (FS) < 40%) were then randomly assigned to vehicle (n=8), auraptene low-dose (5 mg/kg/day, n=7), or high-dose (50 mg/kg/day, n=7). Oral daily treatments with these agents were continued for 6 weeks. There were no differences in left ventricle (LV) geometric and functional data among the 3 MI groups before treatment. After treatment, LVFS was significantly higher in the auraptene low-dose (21%,
p
< 0.0001) and high-dose (26%,
p
< 0.0001) groups than the vehicle group (16%). LV wall thickness in the remote non-infarct area was significantly thinner in the auraptene low-dose (1.4 mm,
p
< 0.01) and high-dose (1.2 mm,
p
< 0.0001) groups than the vehicle group (2.5 mm). Histological analysis demonstrated that auraptene treatment significantly suppressed MI-induced increases in myocardial cell diameter and perivascular fibrosis compared with vehicle treatment. Moreover, auraptene also prevented the activations of ANF and MCP-1 mRNA levels and up-regulated mitochondrial- and lipid metabolism-related gene transcriptions in LV.

Conclusions:
Auraptene treatment prevents the worsening of LV systolic function and represses hypertrophy after MI in adult rats. A natural compound, auraptene is expected as a novel useful agent for heart failure therapy in humans.
Abstract 12078: Obese Girls With PCOS Have Evidence of Vascular Stiffening and Left Ventricular Hypertrophy Which Relate to Insulin Resistance
Authors: Cree-Green Melanie , Truong Uyen , Dorosz Jennifer L. , Moreau Kerri , Coe Gregory , Baumgartner Amy , Newnes Lindsey , Nadeau Kristen J
Published: July 2021

Introduction:
Women with polycystic ovarian syndrome (PCOS) have evidence of greater plaque formation and vascular disease by the third decade of life compared to women without PCOS. We previously reported that obese girls with PCOS have a more atherogenic lipoprotein particle size profile compared to controls. It was unknown these youth also already had evidence of cardiac or vascular disease and plaque development.

Hypothesis:
We hypothesized that adolescent girls with PCOS have evidence of vascular stiffness and plaque formation.

Methods:
Sedentary, non-diabetic, obese girls with PCOS (OBP; N=38, age 14.9±0.2 years, BMI% 98.1±0.3) and without PCOS (OB; N=14, age 14±0.5 years, BMI% 97.4±0.7) were enrolled. Girls with clinical hypertension, renal disease or structural cardiac abnormalities were excluded. Measures included carotid IMT (CIMT), resting echocardiogram, blood pressure, serum lipid profile, and insulin sensitivity assessed with a hyperinsulinemic euglycemic clamp. Calculated measures included carotid beta- stiffness index and distention.

Results:
Resting blood pressures were normal for age and similar between groups. OBP had greater carotid vascular stiffness than OB (βstiffness 1.91±0.08U OB vs 2.19±0.09 OBP, p=0.01; Distention 0.23±0.17mm OB vs 0.18±0.01 OBP, P=0.0007), and there was evidence of greater left ventricular posterior wall thickness (0.79±0.03cm OB vs 0.88±0.02 OBP; P=0.02) and intraventricular wall thickness (0.77±0.04cm OB vs 0.86±0.02 OBP; P=0.04). There was no difference in CIMT between OBP and OB (0.45±0.02cm OB vs 0.48±0.01 OBP, P>0.1). However, OBP were also more insulin resistant than OB (glucose infusion rate 18.3±2.3 mg/leankg/min OB vs 10.4±1.6 OBP, P=0.0007), which correlated with left ventricular posterior wall thickness (R=-0.50, P<0.001).

Conclusions:
Obese normotensive girls with PCOS have vascular stiffening and left ventricular remodeling which relate to insulin resistance. They do not yet have increased CIMT, however, they have insulin resistance and a more atherogenic lipid profile, indicating that the substrate for imtimal-medial thickening and plaque formation is present. Interventions to prevent cardiovascular disease should begin in adolescence.
Abstract 12280: Endothelial Cell Inflammation and Antioxidant Capacity are Associated With Exercise Performance and Microcirculation in Patients With Peripheral Artery Disease
Authors: Gardner Andrew W , Parker Donald E , Montgomery Polly S , Sosnowska Danuta , Casanegra Ana I , Ungvari Zoltan , Csiszar Anna , Sonntag William E
Published: July 2021

Background:
We determined whether exercise performance and lower extremity microcirculation were associated with endothelial cell inflammation, oxidative stress, and apoptosis, and with circulating biomarkers of inflammation and antioxidant capacity.

Methods:
One hundred sixty symptomatic patients with PAD were characterized on the endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells. Patients were further evaluated on circulating inflammatory and vascular biomarkers, physical examination, medical history, exercise performance measured during treadmill evaluation by peak walking time (PWT), and claudication onset time (COT), and lower extremity microcirculation measured by calf muscle hemoglobin oxygen saturation (StO
2
) during treadmill exercise.

Results:
In the multivariate regression model for PWT, the significant independent variables included ankle-brachial index (p<0.001), age (p=0.017), hydroxyl radical antioxidant capacity (HORAC) (p=0.008), and endothelial cell NF-κB activity (p=0.015). In the multivariate regression model for COT, the significant independent variable was endothelial cell NF-κB activity (p=0.013). In the multivariate analyses for the average rate of decline in calf muscle StO
2
during exercise, the significant independent variables included body mass index (p<0.001) and HORAC (p=0.024).

Conclusions:
Endothelial cell inflammation and circulating biomarkers of inflammation and antioxidant capacity are significant factors for exercise performance and microcirculation of the ischemic calf musculature during exercise. The clinical implication is that interventions designed to alleviate endothelial cell inflammation and circulating inflammatory biomarkers, such as antioxidant therapy, may improve exercise performance of symptomatic patients with PAD.
Abstract 12292: GsMTx4-D is a Cardioprotectant Against Myocardial Infarction During Ischemia and Reperfusion
Authors: Wang Jinli , Sun Wanqing , Techiryan George , Sachs Frederick , Suchyna Thomas , Li Ji
Published: July 2021

Introduction:
Reperfusion of ischemic cardiac tissue by percutaneous coronary intervention has become a routine treatment for acute ST-elevation myocardial infarction. However, restoring blood flow to ischemic cardiac tissue can injure myocytes that were viable prior to reperfusion. The putative causes of ischemia/reperfusion (I/R) injury are varied, though cation imbalance has long been known to be a significant contributor. GsMTx4 peptide is a selective inhibitor of cation selective mechanosensitive ion channels (MSCs) and has helped establish the role of MSCs in cardiac physiology. However, the role of MSCs in ischemic reperfusion injury remain uncertain.

Hypothesis:
Pathological stresses from swelling and hypercontracture during I/R can activate cationic MSCs, the D enantiomer of GsMTx4 can act as a cardioprotectant during I/R.

Methods:
GsMTx4-D pharmacokinetics in the plasma and heart was monitored over 24 h using an LCMSMS assay. The cardioprotective activities of GsMTx4 were monitored in a mouse model of ischemia/reperfusion (I/R) injury in which the left anterior descending coronary artery (LAD) was occluded and then released. The influence of GsMTx4 on contractile function and transient calcium signaling of cardiomyocyte were assessed by SoftEdge MyoCam system.

Results:
GsMTx4-D reduced infarct area by >40% for both acute and pretreated animals relative to vehicle injected animals (p<0.01). Cardiac output was significantly improved in GsMTx4-D pretreatment group, and arrhythmias were also significantly reduced by intravenous injections of GsMTx4-D. The further studies with isolated cardiomyocytes revealed that GsMTx4-D improved contractility and intracellular transient calcium signaling of cardiomyocytes under hypoxia/reoxygenation conditions. The immunoblotting data demonstrated that administration of GsMTx4-D attenuated I/R-induced inflammatory c-Jun N-terminal protein kinase (JNK) and NF-κB signaling pathways in the hearts.

Conclusions:
GsMTx4-D is a potent cardioprotectant that decreases infarct area, improves heart function, reduces arrhythmias and attenuates inflammatory signaling pathways that are caused by I/R. Thus GsMTx4-D could be a useful therapy in treating cardiac I/R injury.
Abstract 12358: Abnormal Left Ventricular Midwall Fractional Shortening and Elevated Circulating Biomarkers Predict High Mortality in Elderly Individuals in the General Population
Authors: Masson Serge , Agabiti Nera , Mureddu Gian Francesco , Mayer Flavia , Rolny Vinzent , Vago Tarcisio , Wienhues-Thelen Ursula-Henrike , Boccanelli Alessandro , Latini Roberto ,   on behalf of the Investigators of the PREDICTOR Study
Published: July 2021

Background:
Individuals in the general population with a minimal elevation of cardiac biomarkers and left ventricular hypertrophy are at high cardiovascular risk and may be candidate for early strategies of prevention and treatment. We investigated the combination of several circulating biomarkers with abnormal midwall fractional shortening (MFS), an early echocardiographic indicator of preclinical systolic dysfunction, with adverse outcomes.

Methods:
Circulating levels of N-terminal probrain natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin T (hs-cTnT), and intercellular adhesion molecule-1 (ICAM-1) were measured in 550 elderly community-dwelling individuals (65-84 years) from the PREDICTOR study. Participants were referred to cardiology centers for clinical examination and Doppler echocardiography with centrally-measured MFS. Causes of death or hospitalization were available after a median follow-up of 46 [39-54] months from record-linkage of administrative data.

Results:
Individuals with LV midwall dysfunction (MFS<15%, n= 204 (38%)) had higher levels of NT-proBNP (148 [57-311] ng/L), hs-cTnT (7.3 [3.9-11.6] ng/L)and ICAM-1 (211 [177-261] ng/mL) than those with normal function (82 [42-171] and 5.0 [3.0-8.3] ng/L, 193 [165-230], respectively, p<0.001). The cumulative incidence of total mortality (n=36) among individuals with abnormal MFS and elevated NT-proBNP (>75th age- and sex-specific percentile) was 14%
vs.
2% (abnormal MFS, low NT-proBNP), 6% (normal MFS, high NT-proBNP) and 1% (normal MFS, low NT-proBNP). Corresponding values for hs-cTnT (> 3ng/L) were 14, 0, 5 and 3% (p<0.0001) and 15, 5, 7 and 2% for ICAM-1 above median concentration (all p<0.0001). After adjustment for sex, age, eGFR and hypertension, subjects with abnormal MFS and an elevated biomarker had a higher risk of total mortality compared to those with normal MFS and low biomarker: HR = 11.4 [1.5-87.7] (p=0.02) for NT-proBNP and 7.4 [2.1-25.6] (p=0.002) for ICAM-1, but not for hs-cTnT. Similar trends were seen for GDF-15.

Conclusions:
Elevation of circulating biomarkers combined with early alterations in LV systolic function with MFS identifies a subgroup of individuals in the general population aged 65 or more at higher risk for mortality.
Abstract 12585: Antianginal Efficacy of Ivabradine in Patients With History of Coronary Revascularization
Authors: Zarifis Ioannis , Grammatikou Violetta , Kallistratos Emmanouil , Katsivas Apostolos
Published: July 2021

Introduction:
Coronary revascularization procedures are widely performed for the symptomatic treatment of patients with coronary artery disease (CAD). Even after such procedures, angina symptoms often remain.

Hypothesis:
To evaluate the antianginal effectiveness and the effect on quality of life of ivabradine co-administered with a β-blocker, during 4-month therapy of CAD patients with a history of coronary revascularization.

Methods:
This is a post hoc analysis (926 post-revascularization patients) of a Pan-Hellenic, prospective, non interventional study including 2403 patients with CAD and stable angina. Data were recorded at baseline, and at 1 and 4 months after inclusion, while patients’ quality of life was assessed by means of the EQ-5D questionnaire.

Results:
Of 926 CAD patients who participated in the study, 28 (3%) prematurely discontinued treatment. Addition of ivabradine decreased mean heart rate from 80.3±9.5 bpm (1st visit) to 67.8±7.3 bpm (2nd visit) and 63.9±6.2 bpm (3rd visit) (P<0.001). Mean number of angina attacks and nitroglycerin consumption decreased, respectively, from 2.2±2.3/1.5±2.2 times/week (1st visit) to 0.5±1.0/0.3±0.8 (2nd visit) and 0.3±0.6/0.1±0.4 times times/week (3rd visit) (P<0.001). Moreover, the percentage of patients with angina CCS I (Canadian Cardiovascular Society classification) increased from 36% at baseline to 83% at study completion (P<0.001), while those with angina CCS III-IV decreased from 21% to 2% (P<0.001). All dimensions of the EQ-5D questionnaire were significantly improved after 4 months of treatment with ivabradine (P<0.001) (Table 1). Compliance with ivabradine treatment was high. Throughout the trial, 884 patients (95.5%) were taking their treatment “every day” or “quite often.”

Conclusions:
These results confirm the antianginal effectiveness as well as the beneficial effect of ivabradine on the quality of life of patients with CAD and a history of coronary revascularization.
Abstract 12655: Cardiac Pacing Alters Neural Information Processing in the Intrinsic Cardiac Nervous System
Authors: Rajendran Pradeep S , Vaseghi Marmar , Armour J Andrew , Ardell Jeffrey L , Shivkumar Kalyanam
Published: July 2021

Introduction:
Cardiac pacing is an established therapy; however, it may have detrimental effects on cardiac neurohumoral control. We investigated the effects of pacing on the intrinsic cardiac nervous system (ICNS), an important coordinator of regional cardiac function.

Methods:
Activity from intrinsic cardiac (IC) neurons in the ventral interventricular ganglionated plexus (VIV GP) was recorded using a linear microelectrode array in 5 normal pigs. Changes in IC activity were evaluated in response to epicardial pacing (current: 6 mA; pulse width: 2 ms) at 10% above resting heart rate at the following sites: (1) right atrial appendage (RAA), (2) right ventricular (RV) apex, and (3) left ventricular (LV) posterolateral wall.

Results:
A total of 72 IC neurons were identified. The proportion of neurons responding to pacing was 23% at RAA, 27% at RV apex, and 27% at LV posterolateral wall. Pacing at each site caused significant activation (p < 0.01), significant suppression (p < 0.01), or no change in firing rate of different subsets of neurons. Of all sites, the largest change in firing rate from basal activity was at the LV posterolateral wall, with a significant increase of 1.38 Hz (p < 0.01) in neurons activated by pacing and a significant decrease of 0.63 Hz (p < 0.01) in those suppressed by pacing (Figure 1). There was also a significant difference in basal activity between neurons activated by pacing versus those suppressed by pacing (p < 0.01).

Conclusions:
Our results suggest that pacing has a site-dependent effect on the ICNS. We observed effects with both atrial and ventricular pacing and that LV posterolateral pacing has the greatest impact on neural activity in the VIV GP. Also, neurons with low levels of basal activity tended to be activated by pacing, and those with high levels of basal activity tended to be suppressed, indicating a state-dependent effect. Modulation of information processing in the ICNS may provide the link between pacing and neuroendocrine activation.
Abstract 12891: Mitral Valve Analysis Adding a Virtual Semi-Transparent Annulus Plane for Improved Visualization of Prolapsing Segments
Authors: Dumont Karl-Andreas , Karlsen Jørn Skaarud , Urheim Stig
Published: July 2021

Introduction:
Three-dimensional echocardiography has improved the preoperative evaluation of mitral valve disease. Though, better tools to quantify the amount of prolapsing tissue is warranted. A novel 3D holographic display (Setred AS, Oslo, Norway) offer a 3-dimensional echocardiographic presentation without the need for stereo glasses. We have developed a semi-transparent annulus plane presentation that may better quantitate the prolapsing tissue.

Hypothesis:
We assessed the hypothesis that it is feasible to create a semi-automatic, semi-transparent annulus plane visualized on the holographic display, demonstrating the prolapsed segment that crosses the virtual mitral valve plane.

Methods:
Eight patients with degenerative mitral valve disease were analysed. Three-dimensional transthoracic echocardiography was obtained from an apical view and data was converted to the holographic display for further analysis. Findings were compared with visual inspection during surgery. A semi-automated tool was used to detect the annulus; placement of annulus points was done by clicking out points at small rotation intervals around a rotation center point while rotating around the long axis. After a full rotation, the plane was triangulated using a delaunay triangulation process and the annulus plane was visualized as a semi transparent blue surface. The dataset could then be shown from surgeons view in order to see where the valve crosses the visualized valve plane.

Results:
A total of 48 segments were analysed. We were able to obtain an annulus plane in all and by adding the annulus mitral valve plane, the prolapsing segments could be reproduced in all cases. Figure 1 shows representative recordings (surgeons view) demonstrating a P2 prolapse in the upper panel and a large A2 prolapse in the lower panel.

Conclusion:
In conclusion, the presentation of a semi-transparent annulus plane was feasible and the findings correlated well with that observed during surgery.
Abstract 12989: Generalizability of Quantitative Angiographic In-Segment Late Lumen Loss Imaging in Eastern and Western Populations: Can We Facilitate Global Drug Eluting Stent Evaluation?
Authors: Radhakrishnan Vaishnavi , Allen John C , Fisher Rebecca , Lye Weng Kit , Harrison Robert W , Krucoff Mitchell W
Published: July 2021

Background:
Regulators require mechanistic observations of late lumen loss (LLL) in evaluating new drug eluting stents (DES). Redundant requirements for follow-up catheterization across regulatory jurisdictions worldwide could be reduced if independent core laboratory quantitative coronary angiography (QCA) findings were generalizable. Our study aim was to assess comparability of QCA LLL in East (Japan, China) and West (N. America, Europe) pts using the world’s largest compilation of late follow-up QCA data.

Hypothesis:
The propensity adjusted mean difference in QCA in-segment LLL between East and West is ≤0.4mm, with 95% confidence.

Methods:
All available data from 4 manufacturers (7157 pts, 29 trials) reporting 6-12mo QCA LLL were compiled. East vs West were compared unadjusted and via propensity score (PS) quartiles that adjusted for 26 clinical descriptive and anatomic variables affecting QCA LLL. Of the 7157 pts, 6163 (86%) had complete covariable profiles and comprised the analysis set. Based on consensus of experts and regulators, a clinically meaningful difference between East and West mean IS-LLL was prospectively set at 0.4mm.

Results:
Of 6163 pts, 4134 were West and 2029 East, including 2304 paclitaxel, 1455 everolimus, 1562 zotarolimus, 440 sirolimus and 402 biolimus exposures. Unadjusted and adjusted IS-LLL (Mean±SD) was 0.25±0.47 (W) and 0.08±0.41 (E), and 0.24±0.45 (W) and 0.13±0.45 (E), respectively; differences (95% CI) were 0.17 (0.15, 0.19) and 0.12 (0.08, 0.16), respectively. PS-adjusted IS-LLL is shown the Figure. All differences were ≤ 0.4mm.

Conclusion:
In the world’s largest compilation of protocol follow-up across multiple DES platforms, QCA LLL appears generalizable and sufficiently predictive across East and West pts in both unadjusted and adjusted comparisons. This suggests that global DES evaluations can be facilitated by reducing the need for redundant invasive late catheterization across regulatory jurisdictions.
Abstract 13003: Efficacy of Cilostazol on Platelet Reactivity and Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention: Insights From a Meta-Analysis of Randomized Trials
Authors: Toklu Bora , Singh Amita , Feit Frederick , Bangalore Sripal
Published: July 2021

Introduction:
Cilostazol overcomes high on-treatment platelet reactivity (HTPR) and reduce adverse cardiovascular (CV) outcomes after percutaneous coronary intervention (PCI). However, the role for triple antiplatelet therapy (TAPT) with cilostazol in addition to aspirin and clopidogrel after PCI is not well defined.

Methods:
We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials, until May 2014, evaluating TAPT compared with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel alone in patients undergoing PCI and reporting platelet reactivity and/or CV outcomes. The primary platelet reactivity outcome was differences in platelet reactivity unit (PRU) with secondary outcomes of %platelet inhibition and rate of HTPR. The primary CV outcome was major adverse cardiovascular events (MACE), with secondary outcomes of death, cardiovascular death, myocardial infarction (MI), stent thrombosis (ST), target lesion revascularization (TLR), and target vessel revascularization (TVR) as well as safety outcomes of bleeding and drug discontinuations.

Results:
In 17 trials that evaluated platelet reactivity outcomes, the mean PRU value was 47.73units lower with TAPT vs. DAPT (95% CI -61.41 to -34.04, P <0.0001; mean PRU 182.90 vs. 232.65). TAPT also reduced platelet inhibition by 12.71% (95% CI 10.76-14.67, P <0.0001), and led to a 60% reduction in the risk of HTPR (RR=0.40; 95% CI 0.30-0.53) compared with DAPT. Moreover, among the 34 trials that evaluated CV outcomes, TAPT reduced the risk of MACE (IRR=0.68; 95% CI 0.60-0.78), TLR (IRR=0.57; 95% CI 0.44-0.73), TVR (IRR=0.69; 95% CI 0.59-0.81) and stent thrombosis (IRR=0.63; 95% CI 0.40-0.98) with no difference for other outcomes including bleeding, even in trials using drug eluting stents. Drug discontinuation

due to adverse effects was however higher with TAPT vs. DAPT (IRR=1.59; 95% CI 1.32-1.91).

Conclusions:
In patients undergoing PCI, addition of cilostazol to dual antiplatelet therapy results in decreased platelet reactivity and a significant reduction in CV outcomes including stent thrombosis, even in the drug eluting stent era.
Abstract 13223: Structural Equation Modeling Demonstrates only an Indirect Effect of Obesity on Carotid Intima-Media thickness in Adolescents and Young Adults
Authors: Gao Zhiqian , Khoury Philip R , McCoy Connie E , Shah Amy S , Kimball Thomas R , Dolan Lawrence M , Urbina Elaine M
Published: July 2021

Introduction:
Increased carotid intima-media thickness (cIMT) is associated with cardiovascular (CV) events in adults. Thicker cIMT is found in youth with elevated CV risk factors including obesity although biologically plausible reasons for a direct effect are not clear. We hypothesized that obesity affects cIMT only indirectly through other CV risk factors and this could be demonstrated with use of structural equation modeling (SEM).

Methods:
Ultrasound of the right and left common, bulb and internal carotid arteries was performed in 784 adolescent and young adults (10-24 years old, 65% female, 41% Caucasian, 32% T2DM). Demographics, anthropometrics and fasting laboratory data were collected. Traditional multiple regression analyses (MRA) were performed to assess independent determinants of cIMT. Analyses were then repeated with SEM.

Results:
MRA models explained 11%-22% of variation of common, bulb and internal cIMT. Obesity, age, sex and SBP z-score were significant determinants of all cIMT segments. Race, presence of T2DM, HbA1c and non-HDL contributed for some segments. In SEM, latent variable “cIMT” was used to represent the 3 segments of cIMT. Latent variable “BP” was extracted from SBP and DBP z-score. Latent variable “BGC” (blood glucose control) was extracted from fasting glucose and HbA1c. The final SEM explained a larger amount of the variance of cIMT (43%). The largest direct effect on cIMT was age followed by BP, blood glucose control and non-HDL. BMI, another central risk factor in the pathway towards atherosclerosis, only had a significant indirect effect through blood glucose control, BP & non-HDL. CRP had a small indirect effect through blood glucose control. We conclude that traditional CV risk factors have important direct effects on cIMT in adolescents and young adults but adiposity exerts its influence only through other CV risk factors. SEM may be a useful tool in modeling complex biological pathways.
Abstract 13292: A Novel Reproducible Noninvasive Imaging Approach to Quantify Nitric Oxide-mediated Coronary Endothelial Function in Humans
Authors: Iantorno Micaela , Hays Allison G , Soleimanifard Sahar , Steinberg Angela , Schar Michael , Gerstenblith Gary , Stuber Matthias , Weiss Robert G
Published: July 2021

Endothelial release of nitric oxide (NO) is a defining characteristic of non-diseased vascular tissue. Healthy coronary arteries respond to endothelial-dependent stressors with vasodilatation but those with endothelial dysfunction respond with paradoxical vasoconstriction. The combination of new non-invasive 3T coronary MRI methods and isometric handgrip exercise (IHE), has been suggested as a means to noninvasively quantify coronary endothelial function (CEF). However, IHE may trigger neural, neuro-hormonal and other vasoreactive responses; thus, it is unknown whether the IHE-induced coronary response is, in fact, primarily mediated by NO. Furthermore, it is not known whether the MRI-IHE test is reproducible over time.To test the hypothesis that the IHE-induced coronary response is NO-mediated, we performed MRI-IHE studies before and during the infusion of monomethyl-L-arginine (L-NMMA, 0.3mg/kg/min), a NO synthase inhibitor in 8 healthy subjects. To study reproducibility we performed 2 MRI-IHE studies ~8 weeks apart in 8 coronary artery disease (CAD) patients and 9 healthy subjects. Changes from rest to IHE in coronary cross-sectional area (%CSA) and coronary blood flow (%CBF) were measured with cine MRI. L-NMMA completely blocked coronary vasodilation during IHE (%CSA change 15.4%±2.8% with placebo vs -1.6%±1.3% with L-NMMA; p<0.0001) and the normal increase in coronary blood flow (%CBF change 50.2%±6.7% with placebo vs -2.1%±6.7% with L-NMMA; p< 0.0001). Moreover, there was a strong correlation between repeated measures for %CSA change with IHE at the two exams (R=0.91, p<0.0001) and %CBF change with IHE (R=0.80; p<0.001). Bland-Altman analysis and intra-class correlation coefficients for %CSA and %CBF change with IHE (0.90 and 0.80, respectively) indicated good agreement and little variability between repeated measures. In summary the coronary response to IHE is largely mediated by endothelial-derived NO and is reproducible over several weeks. Thus MRI-IHE is a noninvasive, reproducible tool to assess CEF, arguably the first to noninvasively measure macro- and micro-vascular NO-mediated coronary responses. This noninvasive tool may be useful in future studies of the impact of interventions on CAD pathogenesis.
Abstract 13610: Native T1-based Cardiovascular Magnetic Resonance Imaging for Characterizing Chronic Myocardial Infarctions in Patients
Authors: Kali Avinash , Choi Eui Y , Sharif Behzad , Kim Young J , Bi Xiaoming , Spottiswoode Bruce , Cokic Ivan , Yang Hsin J , Tighiouart Mourad , Li Debiao , Berman Daniel S , Choi Byoung W , Chang Hyuk J , Dharmakumar Rohan
Published: July 2021

Introduction:
Late Gadolinium Enhancement (LGE) Cardiovascular Magnetic Resonance (CMR) is the gold standard for characterizing chronic myocardial infarctions (MIs), but it is contraindicated in patients with end-stage chronic kidney disease.

Hypothesis:
We investigated whether native T1 mapping at 3T can reliably characterize chronic MIs in two pilot patient populations with prior STEMI and NSTEMI.

Methods:
Patients with prior STEMI (n=15) and NSTEMI (n=17) underwent CMR at a median of 13.6 years after acute MI and native T1 maps and LGE images were acquired. Infarct location, size and transmurality were measured from LGE and T1 maps using standard threshold criterion and compared against one another. Visual conspicuity for detecting chronic MI territories on LGE images and T1 maps were assessed by independent reviewers.

Results:
LGE images and native T1 maps were not different for measuring infarct size (STEMI: p=0.87; NSTEMI: p=0.93) and transmurality (STEMI: p=0.19; NSTEMI: p=0.24). Statistical analyses showed good agreement between LGE images and T1 maps for measuring infarct size (STEMI: bias = -0.4±2.1%; R2=0.97; NSTEMI: bias = -1.1±3.9%; R2=0.87) and transmurality (STEMI: bias = 1.5±2.9%; R2=0.99; NSTEMI: bias = -2.2±7.4%; R2=0.71). Sensitivity and specificity of native T1 maps for detecting chronic MIs based on threshold criterion were 93% and 97% respectively (STEMI); and 93% and 92% respectively (NSTEMI). Mean visual conspicuity score for detecting chronic MI on LGE images was greater than that of native T1 maps (p<0.001). Sensitivity and specificity of native T1 maps using visual detection were: 61% and 85% (STEMI); and 67% and 90% (NSTEMI).

Conclusions:
Chronic MIs in STEMI and NSTEMI patients can be reliably characterized using threshold-based detection with native T1 maps when the location of remote myocardium is known. The current visual detectability of remote myocardium on native T1 maps has a certainty of 85% in STEMI and 90% in NSTEMI patients.
Abstract 14707: Effect of Cardiac Resynchronization Therapy (CRT) on Right Ventricular (RV) Function
Authors: Sharma Abhishek , Lavie Carl J , Vallakati Ajay , Goel Sunny , Mukherjee Debabrata , Lichstein Edgar
Published: July 2021

Background:
Right ventricular (RV) dysfunction has been associated with adverse clinical outcomes in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves left ventricular size and function in patients with markedly abnormal ECG QRS duration. However, the effect of CRT on RV function has not been well described.

Objective:
To evaluate change in RV function after CRT.

Methods:
A systematic search of studies published between 1966 to May 2014 was conducted using Pub Med, CINAHL, Cochrane CENTRAL and the Web of Science databases. Studies reporting tricuspid annular plane systolic excursion (TAPSE) or RV basal strain or RV long axis diameter or RV short axis diameter or RV fractional area change (FAC) before and after CRT were identified. A meta-analysis was performed using random effects with inverse variance method to determine the change in various parameters of RV function after CRT therapy.

Results:
Twelve studies (N=1478) were selected for final analysis. CRT therapy led to statistically significant increase in TAPSE [1.32(95% CI 0.67 -1.96; p<0.001)], RV FAC [2.88 (95% CI 0.94; 4.83; p=0.004)] and basal strain [2.03(95% CI 0.81-3.26; p=0.001)] and statistically significant decrease in mean RV long axis [-2.95 (95% CI -5.07; -0.83; p=0.01)] and short axis [- 1.39 (95% CI -2.11; -0.67; p<0.001)] after a mean follow up period of 8.7 months.

Conclusion:
CRT resulted in improved RV size and function as measured by TAPSE, RV FAC, RV basal strain, RV long axis and short axis diameters. Future studies should assess the impact of these changes on symptoms, quality of life and major HF morbidity and mortality.
Abstract 16322: Thiosulfate: A Carrier Molecule of the Protective Effects of Hydrogen Sulfide Against Neuronal Ischemia
Authors: Marutani Eizo , Yamada Marina , Tokuda Kentaro , Shirozu Kazuhiro , Hanaoka Kenjiro , Kaneki Masao , Ichinose Fumito
Published: July 2021

Hydrogen sulfide (H
2
S) is an endogenously produced gaseous signaling molecule that exhibits protective effects in various disease models including cardiac arrest and cardiopulmonary resuscitation. Nonetheless, mechanisms and identity of molecules responsible for the neuroprotective effects of exogenous sulfide donor compounds, such as sodium sulfide (Na
2
S), remain incompletely defined. In circulation, reaction with plasma proteins and or oxidation to sulfur oxides maintains free plasma H
2
S levels very low. Free H
2
S levels only transiently increase and quickly return to its baseline after systemic administration of sulfide donor compounds. Thiosulfate is an oxidation product of H
2
S that is relatively stable in blood and tissues. In the current study, we observed that thiosulfate mediates protective effects of Na
2
S against oxygen glucose deprivation and reoxygenation of human neuroblastoma cell line (SH-SY5Y) and murine primary cortical neurons. We also found that systemic administration of sodium thiosulfate (STS) improved survival and neurological function of mice subjected to global cerebral IR injury. Beneficial effects of STS, as well as Na
2
S, were associated with marked increase of thiosulfate, but not H
2
S, in plasma and brain tissues. These results suggest that thiosulfate is a circulating “carrier” molecule of beneficial effects of sulfide. Protective effects of thiosulfate are associated with modulation of Erk1/2, and JNK pathways and S-sulfhydration of cleaved caspase-3. Of note, we discovered that a SLC13 family protein, sodium sulfate co-transporter 2 (SLC13A4, NaS-2), facilitates the transport of sulfide or thiosulfate across the cell membrane, regulating intracellular concentrations and thus mediating cytoprotective effects of sulfide and thiosulfate. Given that STS is widely used as an antidote and has very low toxicity in humans, these observations suggest that STS represents a novel therapeutic agent for ischemic brain injury.