bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12181: Targeted Intra-Coronary Delivery versus Intra-Myocardial Injection of Therapeutics for Myocardial Recovery: A Nanoparticle Image Guided Porcine Study
Authors: Vekstein Andrew M , Wendell David C , Bowles Dawn E , DeLuca Sophia , Yan Ruorong , Bishawi Muath , Devlin Garth , Asokan Aravind , Poss Kenneth D , Bursac Nenad , Williams Adam R
Published: April 2022

Introduction:
The optimal cardiac delivery route for stem cell and gene therapeutics is poorly understood. Direct intramyocardial (IM) injection has been proposed as the gold standard, however, it is invasive and not studied in detail against targeted intra-coronary (IC) delivery techniques. We sought to compare effectiveness of IM and targeted IC methods using cardiac magnetic resonance imaging (CMR) of nanoparticles in a porcine model.

Hypothesis:
IM provides the highest retention of delivered therapeutic, while targeted IC delivery yields high-volume retention in the perfused coronary territory.

Methods:
In Yorkshire swine (n=10), 5ml of ferumoxytol iron oxide (IO) nanoparticles, similar in size to therapeutic viral vectors, were injected: 1) IM via thoracotomy (n=3), 2) catheter based IC balloon-occlusion (BO) with distal infusion of the LAD (n=4), 3) IC with perforated balloon side wall (SW) infusion in the LAD (n=2), or 4) IC non-selective left main (LM) (n=1). Hearts were harvested and imaged with CMR using T1 and 3D inversion-recovery sequences. Retention of nanoparticles was quantified by percent of myocardium occupied.

Results:
IM delivery yielded the highest retention (16.3±5.5% of myocardial volume, p=0.04). Of the IC approaches, BO had the highest retention (8.7±2.2%, p=0.13 vs IM) compared to SW (5.5±4.9%) and LM (0%). On 3D CMR, BO yielded consistent uptake in the distal LAD territory, including the anterior wall and septum. IM delivery was limited to the anterior wall with no nanoparticles in the septum. Troponin increased 15,600±4,910 with IM vs.184±262 with IC (p=0.14).

Conclusions:
Direct IM injection offers the highest retention of delivered therapeutics to the heart. IC balloon occlusion-distal infusion has highest retention among IC techniques and provides an effective approach to direct therapeutics to the vascular bed most impacted by an infarct.
Abstract 12182: Candesartan vs Lisinopril on Measures of Arterial Stiffness and Wave Reflections in Older, Hypertensive Adults
Authors: Rogers Steven , Liu Chang , Obideen Malik , McDaniel Darius , Hajjar Ihab , Quyyumi Arshed A
Published: April 2022

Introduction:
Higher arterial stiffness independently predicts risk of future cardiovascular events. Although angiotensin converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARBs) reduce blood pressure, their impact on vascular function may vary.

Hypothesis:
We hypothesized differences in the impact of ACEi compared to ARBs on arterial stiffness, wave reflections and microvascular function in hypertension among older men and women.

Methods:
We measured vascular function at baseline and after 1 year in 176 (87 Candesartan, 89 Lisinopril therapy) hypertensive participants with mild cognitive impairment (age 65.9 +/-7.7 years, 57% female). Pulse-wave velocity (PWV), central pulse pressure (CPP) and central augmentation index (AIx) were measured using applanation tonometry and the reactive hyperemia index using digital pulse amplitude tonometry.

Results:
While Candesartan and Lisinopril lowered blood pressure equally, only Lisinopril therapy resulted in a lower PWV (-0.7 ± 0.4 m/s, p=0.03) and CPP (-7 ± 4 mmHg, p=0.01) after 1 year, while Candesartan produced no significant change. There was a significant interaction by sex whereby arterial stiffness was lowered only in women with Lisinopril. Candesartan lowered AIx more than Lisinopril (-4 ± 7% vs -1.5 ± 8%, p=0.05) in both sexes. After adjustment for sex and cardiovascular risk factors, Lisinopril remained a significant predictor of lower PWV and CPP after 1 year (all p<0.05).

Conclusions:
In a cohort of older hypertensive patients, despite equipotent anti-hypertensive effects, Lisinopril was more effective than Candesartan at lowering arterial stiffness in women. Candesartan was effective in lowering wave reflections compared to Lisinopril.
Abstract 12183: Multi-Center Evaluation of Inter-Site Variability in SPECT Myocardial Blood Flow Measurement
Authors: Wells R Glenn , Bengel Frank M , CAMONI LUCA , Cerudelli Elisabetta , Cuddy-Walsh Sarah G , Han Lewis , Kawaguchi Naoto , Keng Felix , Miyagawa Masao , Ratner Hagit , Romsa Jonathan , Ruddy Terrence D
Published: April 2022

Introduction:
Myocardial blood flow (MBF) imaging with SPECT is possible using cardiac-specific cameras. Single-center studies have shown that SPECT MBF is accurate compared with PET MBF and angiography. Clinical implementation requires consistency of SPECT MBF measurements across multiple sites. This study is the first multi-center evaluation of the inter-site processing variability of SPECT MBF.

Objective:
To compare SPECT MBF obtained locally to MBF calculated at the core lab in Ottawa, Canada.

Methods:
Six sites (2 in Canada and one each from Japan, Singapore, Italy, and Germany) each acquired 25 rest/stress MBF studies using Tc99m-tetrofosmin (377 MBq at rest; 1060 MBq at stress) on a pinhole-collimated cadmium-zinc-telluride(CZT)-based cardiac SPECT camera. Patients had intermediate to high pre-test probability of coronary artery disease. MBF was analyzed locally and at a core lab using commercially available software. The time that a room was occupied for a MBF study was compared to that for a standard rest/stress myocardial perfusion study.

Results:
Preliminary results from 4 sites showed a correlation in MBF between the core lab and the local site of an average of 0.96 (range 0.95 to 0.97) at rest and 0.89 (range 0.77 to 0.96) at stress. From Bland-Altman analysis, the mean bias from zero in global MBF between local and core-lab analysis was 3.3% +/- 13.4% at rest and 3.0 % +/- 18.6% at stress. Between the 4 sites, the bias ranged from -4.1% to 9.9% at rest and from -6.3% to 12.8% at stress; the standard deviation (SD) ranged from 10.5% to 14.0% at rest and from 12.0% to 24.5% at stress. There was no significant difference between sites in the SD. The SD of the local-to-core-lab MBF differences is less than the SD of the test-retest difference of 30%, measured in a previous single-center study. The average additional time to perform a MBF study acquisition varied between sites from 45 to 76 min. This additional time includes the time needed to pharmacologically stress the patient which is normally done outside the camera room.

Conclusions:
This multi-center evaluation supports the feasibility of consistently measuring MBF using CZT-based cardiac SPECT cameras, as has been suggested from previous single-center studies.
Abstract 12189: The Ratio of Cyclic Guanosine Monophosphate to Brain Natriuretic Peptide (cGMP/BNP) Stratifies The Risk of Heart Failure Hospitalization in Cardiac Resynchronization Therapy (CRT) Patients
Authors: Ideishi Akihito , Ueda Nobuhiko , Yokoyama Yasuhiro , Kataoka Naoya , Miyazaki Yuichiro , Wakamiya Akinori , Kamakura Tsukasa , Wada Mitsuru , ishibashi kohei , Yamagata Kenichiro , Inoue Yuko , Miyamoto Koji , Nagase Satoshi , Aiba Takeshi , Izumi Chisato , Noguchi Teruo , Minamino Naoto , Kusano Kengo
Published: April 2022

Background:
Cardiac Resynchronization Therapy (CRT) is established treatment for patients with heart failure, however, there are various predictors of prognosis. Although CRT responder is reported to have a better prognosis than CRT non-responder, some cases have poor clinical outcomes even among CRT responders. Meanwhile, brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP) are associated with the severity of heart failure. Little is known about the efficacy of prognostic value of BNP and cGMP in CRT patients especially among CRT responders.

Methods:
Among 246 consecutive CRT patients, we retrospectively analyzed 86 patients whose biomarkers were measured at the time of implantation. The patients were divided into two groups by the median value of cGMP/BNP (0.26). The endpoint was heart failure hospitalization, and the CRT responder was defined as an improvement of end-systolic volume (ESV) ≥ 15% or ejection fraction (EF) ≥ 10% at 6 months after CRT implantation.

Results:
The patients were 65.4 ± 13.6 years old, 64 (74%) patients were male, 17 (20%) patients were ischemic cardiomyopathy, and 47 (55%) patients were CRT responders. During a median follow-up period of 830 (interquartile range: 482-1246) days, 27 patients (31%) had heart failure hospitalization (high cGMP/BNP group: 8 vs low cGMP/BNP group 19, p = 0.016). Kaplan-Meier analysis revealed the risk of heart failure hospitalization was higher in high cGMP/BNP group than in low group (log-rank p = 0.0025), and the same result was observed even among CRT responders (log-rank p=0.018). cGMP/BNP increased in responders (p = 0.0045) but not in non-responders (p = 0.23) at 6 months after CRT implantation in Wilcoxon signed-rank test. Univariate analysis showed that BMI, chronic kidney disease, diabetes mellitus, hemoglobin, CRT responder, and cGMP/BNP were predictors of heart failure hospitalization.

Conclusion:
cGMP/BNP is useful for the heart failure risk stratification in CRT patients.
Abstract 12192: Arterial Tortuosity Syndrome: A Longitudinal Assessment Of Cardiovascular Features
Authors: Salamat Bita , Taylor Andrea , Stephens Sara , Beecroft Taylor , Weigand Justin , Jacob Ben , Morris Shaine A
Published: April 2022

Introduction:
Arterial tortuosity syndrome (ATS) is an ultra-rare arteriopathy caused by pathogenic biallelic variants in
SLC2A10
leading to tortuosity, elongation, and dilation of vessels, and pulmonary artery (PA) stenosis (Fig 1). No studies to date have evaluated the progression of cardiovascular (CV) features, including aortic root (AR) and ascending aorta (AA) dilation.

Hypothesis:
We hypothesize AR and AA dilation progress similar to other aortopathies with increase dimensions but stable z-scores in childhood.

Methods:
A retrospective cohort study of patients at our institution with ATS, defined by homozygous or compound heterozygous
SLC2A10
mutations with consistent phenotypes, from 2000-2021 was conducted. CV imaging, medications, and interventions were reviewed. AR and AA measurements were collected from echocardiographic reports and z-scores were calculated. Dilation was defined as z-score
>
+2. Slopes were calculated using mixed linear regression.

Results:
Six subjects (5 males) aged 1 month-16 years at diagnosis were included. All had AR dilation, 50% had AA dilation, and 50% had main or branch PA stenosis at a given point. CV intervention was only performed in 1 patient who underwent multiple bilateral PA angioplasties and stenting for severe distal branch PA hypoplasia. Three patients were prescribed beta-blockers, of whom one was also prescribed losartan. Figure 2 shows mean slopes for AR and AA changes. No patients had aortic dissection or CV surgery.

Conclusions:
In conclusion, AR and AA dilation persist in ATS but with stable z-scores similar to other aortopathies. Larger sample size investigations may further elucidate the role of medications in ATS.
Abstract 12193: Efficacy and Safety of Rivaroxaban versus Vitamin K Antagonists in the Treatment of Left Ventricular Thrombi: A Meta-Analysis
Authors: Al-abcha Abdullah , Saleh Yehia , Abdelkarim Ola , Ghnaima Harith , Boumegouas Manel , Herzallah Khader , Abela george
Published: April 2022

Introduction:
Left ventricular (LV) thrombus is a well-recognized complication of LV systolic dysfunction, especially in the setting of acute myocardial infarction. Multiple recent studies looked into the efficacy and safety of direct oral anticoagulants but limited number of studies reported outcomes in patients on rivaroxaban specifically.

Hypothesis:
Rivaroxaban is as effective as vitamin K antagonists (VKAs) in the treatment of LV thrombus.

Methods:
We conducted a meta-analysis of all studies that evaluated clinical outcomes of rivaroxaban versus warfarin in the treatment of LV thrombus. The primary outcome was thrombus resolution. Secondary outcomes included bleeding events, and systemic embolism.

Results:
One randomized clinical trial (RCT), and 3 retrospective observational studies with a total of 988 patients were included. Heterogeneity was low-moderate across the trials (19-54%). Thrombus resolution was numerically higher in the rivaroxaban arm but did not reach statistical significance (Rivaroxaban 80% vs VKAs 70%, p=0.57). Bleeding events (Rivaroxaban 9% vs VKAs 11%, p=0.77) and systemic embolism (Rivaroxaban 21.5% vs VKAs 30.9%, p=0.57) were both similar between the two arms (Figure).

Conclusions:
Rivaroxaban has similar efficacy and safety when compared to VKAs in the treatment of LV thrombus. Large RCTs are needed to confirm these results.
Abstract 12199: Sirtuin1 Mediates Pressure Overload-Induced Cardiac Pathological Hypertrophy Through Regulating Mitochondrial Dynamics
Authors: Le Van , Murphy Jiayuan , Fedorova Julia , Bates Lauryn , Yang Yi , Davitt Kayla , Logan Cole , Ren Di , Li Ji
Published: April 2022

Introduction:
Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent histone deacetylase. We revealed that the pressure-overload-induced SIRT1 can exacerbate cardiac systolic dysfunction. But the mechanisms by which SIRT1 undermines cardiac function under pathological conditions remain unclear.

Hypothesis:
SIRT1 induced by pathological hypotrophy disturbs mitochondrial dynamics homeostasis resulting in an exacerbated cardiac dysfunction.

Methods:
Wild-type littermates SIRT1

f/f

(3-5 months) and inducible cardiomyocyte-specific SIRT1 knockout (icSIRT1
-/-
) (3-5 months) C57BL/6J mice were subjected to transverse aortic constriction (TAC) surgery for six weeks. Echocardiography assessed cardiac functions and CODA tail-cuff system measured blood pressure. The mitochondrial dynamics were examined by immunoblotting and transmission electron microscopy (TEM).

Results:
The echocardiography showed that there were significant reductions in ejection fraction (EF) and fractional shortening (FS) of the SIRT1

f/f

mice after 6-weeks of TAC-induced pressure overload. The diastolic and systolic blood pressure were increased in SIRT1

f/f

mice during TAC surgery. Intriguingly, icSIRT1

-/-

versus
SIRT1

f/f

demonstrated significant resistance to pathological hypertrophy caused by TAC-induced pressure overload as determined with echocardiography and blood pressure measurements. The immunoblotting revealed that the six weeks of TAC surgery caused significantly higher levels of the mitochondrial fusion protein, mitofusin 2 (MFN2), in SIRT1

f/f
versus

icSIRT1
-/-
hearts. In addition, TEM data showed more elongated mitochondria in SIRT1

f/f
versus

icSIRT1
-/-
hearts, indicating a critical role of SIRT1 in maintaining mitochondrial dynamic homeostasis under pathological stress conditions. Metabolomics and proteomics showed that SIRT1 regulates carnitine palmitoyltransferase-1 and long-chain acyl CoA dehydrogenase to modulate fatty acid metabolism in response to TAC-induced stress.

Conclusions:
Cardiomyocyte SIRT1 plays a key role in cardiac mitochondrial dynamics during pathological stress conditions. Inhibition of SIRT1 activity could be a good strategy to ameliorate pressure overload-induced hypertrophy.
Abstract 12203: Sotatercept Analog RAP-011 is More Effective Than Sildenafil in Improving Pulmonary Hypertension and Reducing Right Ventricular Hypertrophy in a ZSF1 Rat Model of Heart Failure With Preserved Ejection Fraction
Authors: Joshi Sachindra R , Liu Jun , Andre Patrick , Kumar Ravi , Li Gang
Published: April 2022

Introduction:
Pulmonary hypertension (PH) due to heart failure with preserved ejection fraction (PH-HFpEF) is the most prevalent form of WHO Group 2 PH but lacks effective treatment options. We previously found that sequestration of activins and growth differentiation factors with the sotatercept analog RAP-011, an activin receptor type IIA-Fc fusion protein, reverses pathological remodeling of pulmonary arteries and the right ventricle (RV) in experimental models of pulmonary arterial hypertension (PAH, Group 1 PH). This strategy of selective multi-ligand neutralization offers a promising new approach for treating patients with PAH and is under active clinical evaluation (PULSAR, SPECTRA, and STELLAR). Here, we compared the cardiopulmonary effects of therapeutic treatment with RAP-011 to those of sildenafil in a rat model of PH-HFpEF.

Methods:
PH was induced in adult male obese ZSF1 rats by a single subcutaneous injection of SU5416 (100 mg/kg). To model the timeline of diagnosis and treatment for Group 2 PH patients, we initiated treatment with RAP-011 and sildenafil 8 weeks post SU5416 administration—at which point RV dysfunction is prominent—and continued treatment for 8 weeks. RV systolic pressure (RVSP), pulmonary artery acceleration time (PAAT), RV hypertrophy, and tricuspid annular plane systolic excursion (TAPSE) were evaluated by right heart catheterization and echocardiography following the 8-week treatment regimen.

Results:
Obese ZSF1 rats treated with SU5416 displayed significantly increased RVSP (P < 0.0001) and decreased PAAT (P < 0.0001). RAP-011 treatment fully reversed changes in RVSP (P < 0.0001) and PAAT (P < 0.0001), whereas sildenafil treatment improved RVSP by 19% (P < 0.05) and PAAT by 36% (P < 0.001). Treatment with RAP-011, but not sildenafil, normalized RV hypertrophy (P < 0.0001) and increased TAPSE (P < 0.0001).

Conclusions:
Therapeutic treatment with the sotatercept analog RAP-011 exerted beneficial cardiopulmonary effects in a ZSF1 rat model of PH-HFpEF that were significantly greater than those produced by sildenafil, fully normalizing PH and RV hypertrophy and improving RV function. These findings support evaluation of sotatercept in patients with PH-HFpEF (Group 2 PH).
Abstract 12205: A New Mouse Model of Myocardial Lipids, Fibrosis, Arrhythmia and Diastolic Dysfunction Induced by Hyperlipidemia and Cardiac LDLR
Authors: Williams Monique , Iansen Irion Camila , Condor Capcha Jose Manuel , Lambert Guerline , Seo Grace , Goldberger Jeffrey J , Shehadeh Lina A
Published: April 2022

Background:
Hyperlipidemia is a major risk factor for CVD. Patients with HF with preserved ejection fraction (HFpEF) have more myocardial lipid accumulation than patients with reduced EF (HFrEF). RNASeq data from cardiac biopsies showed downregulation of the gene for lipoprotein lipase (LPL) that degrades triglycerides, in HFpEF patients compared to healthy and HFrEF controls. Poloxamer-407 (p407) induces hyperlipidemia by blocking LPL and subsequent increase in plasma triglycerides and low-density lipoprotein (LDL) cholesterol. We hypothesized that mice treated with p407 and cardiac LDL-Receptor (LDLR) over-expression (OE) develop hyperlipidemia, myocardial lipid accumulation, and diastolic dysfunction resulting in HFpEF and arrhythmias.

Methods:
Baseline cardiac function was assessed by echo for male and female C57Bl6 mice (n=9) for 2 groups: 4wk biweekly i.p. p407-injections with (n=4) or without (n=3) single i.v. injection with AAV9-cTnT-LDLR. Cardiac function was assessed by echocardiography at 3 and 4 wks. Blood Pressure (BP) and Whole Body Plethysmography (WBP) were assessed during wk4. Ttest was used for statistics. PR and ORO staining and telemetry were performed at wk4.

Results:
At wk3, P407 and LDLR OE led to alterations in diastolic function (increased IVCT, IVRT, MV E/E’, MPI, and NFT) and increased LV wall thickness, p<0.05. At wk4, there was pulmonary hypertension (increased mean pulmonary arterial pressure, decreased pulmonary acceleration time
p
<.05).Histology showed excessive myocardial lipids and fibrosis, and telemetry showed incidents of second-degree and higher-degree AV block. The group injected solely with p407 show
e
d alterations in diastolic function (increased IVCT, IVRT, NFT, LVMPI, LVMPI NFT
p<.05
) and decreased EDV, ESV, EDLVM, ESLVM,
p<.05
at wk4. All groups had preserved %EF and no abnormalities in BP or WBP.

Conclusions:
P407 and cardiac LDLR OE induce a drastic decline in cardiac diastolic function over a shorter period of time compared to p407 alone. Diastolic dysfunction was observed in wk3 followed by pulmonary hypertension, arrhythmia, myocardial lipid accumulation and fibrosis in wk4. This new model may allow for more rapid investigations of cardiac abnormalities seen in HFpEF patients.
Abstract 12219: Pre-Treatment With P2Y12 Inhibitor in Patients With Non-ST Elevation Acute Coronary Syndrome; a Meta-Analysis
Authors: Al-abcha Abdullah , Saleh Yehia , El-khatib Layan , Elshafie Ahmed , Ghnaima Harith , Banga Sandeep , Abela george
Published: April 2022

Introduction:
The guidelines for the management of acute coronary syndrome in patients presenting without persistent ST-segment elevation (NSTE-ACS) recommend against the routine use of pre-treatment with P2Y12 inhibitors when early invasive management is planned. Recently, multiple randomized clinical trials (RCTs) were published to compare the efficacy and safety of pre-treatment with P2Y12 inhibitors

Hypothesis:
Pre-treatment with P2Y12 inhibitors improves clinical outcomes in NSTE-ACS.

Methods:
We conducted a meta-analysis of all studies that evaluated clinical outcomes of pre-treatment with P2Y12 inhibitors versus no-pretreatment in the treatment of NSTE-ACS. The primary outcome was 30-days major adverse cardiovascular events (MACE). Secondary outcomes included risk of major bleeding, all-cause mortality, myocardial infarction (MI), and target vessel revascularization (TVR).

Results:
A total of 7 studies, and 103,678 patients were included. In regards to the primary outcome, the rate of MACE was similar between the two groups (OR 0.89; 95% CI 0.67-1.19; p=0.44). On the other hand, the rate of major bleeding was significantly higher in the pre-treatment group when compared to no- pre-treatment (Pre-treatment 2.6% vs control 1.7%, p=0.008). All-cause mortality, risk of MI, and risk of TVR were similar between the two treatment groups (Figure 1).

Conclusions:
Our findings correlate with the ESC guidelines, and we recommend against the routine use of pre-treatment with P2Y12 inhibitors in patients with NSTE-ACS.
Abstract 12224: Predictive Power and Value of a CAD Polygenic Risk Score in Primary Prevention Based on Age and Clinical Risk
Authors: Marston Nicholas A , Pirruccello James , Melloni Giorgio , Kamanu Frederick , Roselli Carolina , Aragam Krishna , Butterworth Adam , Lubitz Steven A , Ellinor Patrick T , Sabatine Marc S , Ruff Christian T
Published: April 2022

Background:
The clinical utility of polygenic risk scores (PRS) for CAD has not yet been established. We investigated the ability of a CAD PRS to potentially guide statin initiation after accounting for age and clinical risk.

Methods:
We performed a prospective cohort study in the UK Biobank that included all individuals without a history of CAD and who were not on lipid-lowering therapy. The CAD PRS was comprised of 241 genome-wide significant SNPs. Genetic risk categories were defined as low (bottom 20%), intermediate, and high (top 20%). HRs were calculated as a function of age. Next, 10-year ASCVD risk score was used to classify individuals as low, borderline, intermediate, or high risk. Each ASCVD risk group was further stratified by genetic risk to determine whether genetics could reclassify individuals to help guide decisions regarding statin initiation with more precision. ASCVD events were defined as incident clinical CAD (including MI), stroke, or CV death.

Results:
The 333,245 patients included in this study were ages 40-74 years (avg 57) and 57% were female. Over the 10-yr follow-up, there were 4,552 MIs. The CAD PRS significantly predicted MI in all age groups but had significantly stronger risk prediction at younger ages (p-int <0.001) (
Figure, A
). This gradient of risk was especially pronounced under 50 years of age, where those with high PRS approached a 6-fold increased risk of MI compared with those in the low PRS category. When CAD PRS testing was added to the 71,534 patients <50 years old, 20% of borderline risk patients were reclassified into intermediate risk, warranting initiation of statin therapy to reduce LDL-C, and 20% of borderline and intermediate risk patients were reclassified as low risk, thus not warranting therapy (
Figure, B
).

Conclusion:
The predictive ability of a CAD PRS is especially strong in individuals under the age of 50 and can be used to identify more precisely who should be initiated on statin therapy.
Abstract 12225: Serum Exosome-miRNAs Profile in Patients With Myocardial Infarction
Authors: Guan Ruicong , zeng kuan , Zhang Bin , Gao Minnan , Li Jianfen , Qiang Yongjia , Liu Yuqiang , Wang Dian , Liu Zhuxuan , Yang Yanqi
Published: April 2022

Introduction:
Circulating miRNAs have been found to have different expressions in acute myocardial infarction. Profile of serum exosome-miRNAs in patients with myocardial infarction is unknown. In the present study serum exosome-miRNAs in patients with ST elevated myocardial infarction (STEMI) and in healthy individuals were assessed and highly specific exosome-miRNAs were selected.

Hypothesis:
Specific serum exosome-miRNAs play important roles in the pathological changes of patients 3-6 months after STEMI.

Methods:
Totally 28 patients with ages from 54 to 80 years, and 25 males among them 3-6 months after STEMI and 35 healthy with ages from 24 to 46 years, and 25 males among them were included in this study. The serum exosome-miRNAs were assessed by using microarray assay (IIIumnia Hiseq 2500). Profile of serum exosome-miRNAs related to heart diseases was established in both the patients and healthy individuals. The specificity of the highest and lowest expressed exosome-miRNAs in the patients were evaluated by using quantitative real-time polymerase chain (qPCR).

Results:
In comparison with the healthy, 28 up-regulated miRNAs and 49 down-regulated miRNAs were found in patients 3-6 months after STEMI (p<0.01). Among them, 25 up-regulated miRNAs and 13 down-regulated miRNAs were listed in the miRNA database with confirmed relation to heart diseases. Three highest expressed miRNAs were hsa-miR-23a-3p (1.42 folds), hsa-miR-224-5p (3.25 folds) and hsa-let-7d-3p (1.41 folds), and two least expressed ones were hsa-miR-874 (0.48 folds) and hsa-miR-181a-3p (0.63 folds) (AUC 0.81 and 0.77), which demonstrated significant specificity for pathological changes in the patients according to qPCR test.

Conclusions:
The exosome hsa-miR-23a-3p, hsa-miR-224-5p, hsa-let-7d-3p, hsa-miR-874 and hsa-miR-181a-3p may play important roles in patients 3-6 months after STEMI.
Abstract 12259: Early Mechanical Signs of Myocardial Injury in a Model of Systemic Inflammation
Authors: Maiorov Ida , Livneh Amit , Efraim Roi , Landesberg Amir
Published: April 2022

Introduction:
Early detection of myocardial dysfunction in severe inflammations, as myocarditis COVID-19 and sepsis, is of great merit.
We hypothesized
that metalloproteinases (MMPs) discharge from activated macrophages and leukocytes dismantles the extracellular matrix (ECM), leading to diastolic and systolic dysfunctions.

Methods:
The right and left ventricle functions were studies in a unique Langendorff setup, with computer controlled preloads and afterloads, utilizing rat hearts (n=7). Collagenase (MMP8) was added to the Krebs-Henseleit solution after the baseline recording. Pressure-Area loops and changes in the cardiac geometry were continuously recorded by short-axis ultrasound cines (15MHz, 20 fps) of both ventricles.

Results:
ECM dismantling caused immediate systolic and diastolic dysfunctions, especially in the LV. Significant decreases in the LV systolic pressure and EDV developed with overt shift of the end-diastolic pressure-volume relationship toward lower volumes. The decrease in the EDV was associated with myocardial wall thickening. After collagenase perfusion yielded 10% drop in systolic pressure, LV EDV at EDP of 12 mmHg dropped by 20.0±17.2 % (p=0.04) and LV wall volume increased by 3.39±3.68 % (p=0.04), without significant changes in the epicardial diameter. Consequently, both diastolic stiffness to volume ratio (S2V) of the diastolic elastance to EDV, and myocardial wall thickness to cavity area ratio (W2C) significantly increased. S2V and W2C increased by 1.48±0.51 and 1.32±0.34 folds relative to baseline, respectively (p=0.03, p =0.03). S2V and W2C increased by 1.82±0.71 and 1.52±0.46 folds, respectively, after 20% drop in systolic pressure (p= 0.02, p=0.02). An intact ECM is essential for the diastolic recoil. Dismantling the ECM diminishes the diastolic recoil and increases diastolic stiffness. Interestingly, the right ventricle presented similar trends, but the changes were insignificant, and the RV was less vulnerable to damage.

Conclusion:
ECM degradation causes severe systolic and diastolic dysfunctions. Novel indices (S2V and W2C) for early detection of myocardial involvement in severe inflammatory diseases were developed.
Abstract 12267: Impact of a Comprehensive ST-Elevation Myocardial Infarction Protocol on Key Process Metrics in African American STEMI Patients
Authors: Nair Raunak , Kassis Nicholas , Kumar Anirudh , Huded Chetan P , Johnson Michael J , Kravitz Kathleen A , Reed Grant W , Krishnaswamy Amar , Menon Venu , Lincoff A M , Meldon Stephen , Kralovic Damon M , Kapadia Samir R , Khot Umesh N
Published: April 2022

Background:
Optimizing STEMI care processes for African Americans is a critical matter with important public health implications. We aimed to study if a comprehensive ST-elevation myocardial infarction (STEMI) protocol (CSP) could improve key process metrics in the African American (AA) population.

Methods:
We developed a 4-step CSP which included, 1) Emergency Department catheterization lab activation; (2) STEMI Safe Handoff Checklist; (3) immediate catheterization lab transfer; (4) and radial-first percutaneous coronary intervention (PCI). Baseline characteristics and procedural characteristics were compared between all consecutive STEMI patients who underwent PCI at the Cleveland Clinic main campus between January 1, 2011, to July 14, 2014 (pre-CSP group) and July 15, 2014, to July 15, 2019 (post-CSP group).

Results:
There were a total of 208 AA patients in the pre-CSP group compared to 271 AA patients in the post-CSP group. Baseline characteristics were quite similar between the two groups except for a lower rate of MI in the post-CSP group (45% vs 30%, P=0.001). After implementation of our CSP, guideline-directed medical therapy increased from 71.6% to 81.9% (P=0.011), radial utilization went up from 14.4% to 73.8% (P<0.001), door to balloon time decreased from 90 minutes (median IQR 64-120) to 70 minutes (median IQR 45-95) (P<0.001), fluoro dose decreased from 1610 mGy (median IQR 980.25-2592.25) to 1147 mGy (median IQR 742-1844) (P<0.001), and contrast dose decreased from 197.07 ml to 152.98 ml (P<0.001).

Conclusion:
Implementing a CSP was able to significantly improve the key STEMI process metrics for African American patients. Optimizing key STEMI process metrics is an important initiative to ensure equitable STEMI care.
Abstract 12270: The Evolution of Tricuspid Regurgitation After Percutaneous Patent Ductus Arteriosus Closure in Ex-Preterm Infants Under 2 Kilograms
Authors: Rodriguez Franco Salvador A , O’Callaghan Barry , Zablah Jenny E , Morgan Gareth J
Published: April 2022

Objective:
To evaluate incidence and evolution of new tricuspid regurgitation (TR) after percutaneous patent ductus arteriosus (PDA) closure in preterm infants under 2 kg.

Background:
Multiple advances in techniques and technology in cardiac catheterization have facilitated percutaneous closure of neonatal PDAs. A higher rate of complications has been suspected in this setting, but robust scientific evidence concerning this association is not yet available. TR has been a recognized significant complication, gaining notoriety with the use of the Piccolo device over the last few years.

Methods:
We performed a single-center retrospective cohort study. We included 29 patients under 2 kg who underwent percutaneous PDA closure between January 2019 and December 2020. This cohort was then matched with a control group of sub 2 Kg patients who did not have percutaneous PDA closure at a ratio of 2:1 (n=58). Echocardiographic data points were collected prior to catheterization and at intervals up to 1-year post-procedure. To standardize the temporal change in TR, we measured the zone of convergence and normalized it with the body surface area related to time.

Results:
TR after percutaneous PDA closure was seen in 9 cases (31.1%), of which 8 cases were classified as mild-to-moderate (27.6%) and 1 case as severe (3.4%). At the end of follow-up, TR persisted in 5/9 cases (17.2%); however, no increases in TR, clinical complications, or need for reintervention were noted for these patients. In the control group of 58, we incidentally noted two patient with moderate to severe TR which diminished over time. Compared to the control group, our cohort did not present significant difference in terms of survival or weight gain characteristics.

Conclusions:
TR remains a worrying likely mechanical consequence of catheter and device manipulation in percutaneous preemie duct closure. We should strive to decrease such complications by technical and procedural improvement. Despite this, no patient in our cohort has required specific medical or surgical reintervention for TR, and the echocardiographic trend is tending towards a decreasing grade of TR over time.
Abstract 12273: Correlation Between Aortic Strain and Native T1 Value in Hypertrophic Cardiomyopathy
Authors: Hachiya Shoko , Kosuge Hisanori , Fujita Yasuhiro , Hida Satoshi , Tomiyama Hirofumi , Chikamori Taishiro
Published: April 2022

Introduction:
Aortic stiffness is related to impairment of left ventricular (LV) function and LV remodeling. Myocardial ischemia and fibrosis in hypertrophic cardiomyopathy (HCM) cause ventricular arrhythmia and sudden cardiac death. Magnetic resonance imaging (MRI) can evaluate aortic stiffness and LV function noninvasively. Aortic strain shows the possibility for the assessment of the aortic status and T1 mapping allows the assessment of diffuse myocardial fibrosis.

Hypothesis:
We assessed the hypothesis that aortic strain is correlated with native T1 values in HCM patients.

Methods:
Thirty-six HCM patients (mean age : 64±2 years) and forty control subjects (mean age : 58±3 years) with no history of coronary artery disease were examined using a 3T MRI. Cross-sectional aortic areas of the descending aorta were measured and aortic strain was calculated as follows: aortic strain (%) = (maximum aorta area - minimum aorta area)/minimum aorta area х 100. Native T1 values were measured as an averaged T1 values in the septum of 3 short-axis slices of base-to-apex left ventricle myocardium. LV ejection fraction (LVEF), left atrium (LA) dimension and E/e’ were measured by echocardiography.

Results:
LVEF showed no significant differences between HCM patients and control subjects (66.2±1.1% vs. 64.5±1.0%, p=0.2488). LA dimension and E/e’ in HCM patients were significantly higher than control subjects (LA dimension: 38.3±1.1mm vs 34.9±0.85mm, p=0.0155, E/e’: 13.4±0.95 vs 9.2±0.42, p<0.0001). Native T1 values and aortic strain of the descending aorta in HCM patients were significantly lower than those in control subjects (native T1 values: 1254±8ms vs 1208±8ms, p<0.0001, aortic strain: 7.95±0.66% vs 12.92±1.27%, p=0.0012). Multiple linear regression analysis revealed that aortic strain was correlated with age (β=-0.370, p=0.0014) and native T1 values (β=-0.244, p=0.0448).

Conclusions:
In HCM patients, aortic strain of the descending aorta was significantly decreased compared to control subjects and correlated with native T1 values. Aortic strain may be a promising factor for myocardial fibrosis in HCM patients.
Abstract 12277: Concordance of High Polygenic CAD Risk Score With High Coronary Artery Calcium Score & Low Polygenic CAD Risk Score With Low Coronary Artery Calcium Score: A Real World Experience
Authors: Saad Shaukat Muhammad Hamza , stys patryk , Sjovold Alexander , Hajek Catherine , Petrasko Phillip , Pham Melissa , Stys Veronica , Petrasko Mark , Rynders Beatrice , Singh Komaldeep , Coy Kevin , Herman Michael , Sincan Murat , Stys Adam , Petrasko Marian S , Stys Tomasz
Published: April 2022

Introduction:
Genetic predisposition for CAD is well established. Polygenic risk scores are emerging as tools which attempt to quantify the genomic component of an individual’s risk for CAD. However, clinical utility for individual risk stratification is unclear.

Hypothesis:
180 SNPs previously identified in Caucasian Genome Wide-Association Studies for CAD were used to construct a weighted restricted polygenic risk score (PRS; normalized range 11.18 -17.58). This study hypothesizes that high PRS (>=85th percentile) is associated with high (>400) coronary artery calcium (CAC) score, & a low PRS(< 85th percentile) is associated with low (<100) CAC.

Methods:
Between January 2018 and March 2020, 21,784 patients underwent CAC screening and/or PRS testing. Caucasian patients with both PRS and CAC scores were reviewed. Patients with CAC 100-400 were excluded. Fisher’s exact test for high/low PRS and high/low CAC was utilized.

Results:
2,752 patients were identified to have low (<100) or high (>400) CAC; 306 (11.1%) had a high CAC (table 1). Odds ratio of high PRS associated with high CAC and low PRS associated with low CAC was 1.54 (95% CI: 1.07-2.19; p=0.017).

Conclusion:
Our real-world experience in a Caucasian cohort shows that high PRS is associated with a high CAC, as is a low PRS with low CAC. Concordance between PRS and CAC lends support for incorporating PRS in the clinical setting, especially for early identification of individuals at high risk for CAD. Larger, ethnically diverse studies are needed.
Abstract 12282: Mismanagement of Hypertension: ColausPsycolaus Study
Authors: Chekanova Valeriya , Marques-Vidal Pedro-Manuel
Published: April 2022

Introduction:
The importance of genetic factors in management of hypertension in a population setting is unclear.

Hypothesis:
To identify the clinical and genetic factors associated with poor control of hypertension in the Swiss population.

Methods:
Data from first (2009-2012) and second (2014-2017) follow-ups of a population-based, prospective study conducted in Lausanne, Switzerland. Management of hypertension was assessed according to the ESC guidelines based on the 140/90 or the 130/80 mm Hg thresholds. Two genetic risk scores for hypertension (18 and 28 SNPs) and 133 individual SNPs related to response to specific antihypertensive drugs were tested.

Results:
1073 and 1157 participants of first and second follow-ups were included. The prevalence of controlled participants using the 140/90 threshold was 58.8% and 63.6% in first and second follow-ups, respectively. Using the 130/80 threshold, the prevalence rates were 31.4% and 34.0%, respectively. On multivariable analysis, using the 140/90 threshold, older age was negatively associated to hypertension control. Using the 130/80 threshold, older age and increased BMI were negatively associated while total number of drugs was positively associated with hypertension control. The associations with gender, education, alcohol drinking and antidiabetic drug treatment varied between surveys and thresholds. No consistent associations were found between genetic risk scores and hypertension control for both surveys and both thresholds. Finally, no significant association was found between individual SNPs and hypertension control according to antihypertensive drug used.

Conclusions:
Control of hypertension is poor in Switzerland, namely among older adults and possibly among overweight or obese subjects. No association between genetic scores or individual SNPs and hypertension control could be found.
Abstract 12286: Pregnancy Outcomes in Pulmonary Hypertension With Congenital Heart Disease: A Multicenter Experience From 2220 Cases
Authors: Zhang Qian
Published: April 2022

Background:
Cardiovascular disease is a global burden for women’s health. Pregnancy with pulmonary hypertension associated with congenital heart disease (CHD-PH) is related to prohibitive maternal mortality. According to the latest AHA scientific statement, their pregnancies are contraindicated, regardless of their CHD diagnosis and PH severity. Considering the emerging population of CHD-PH reaching the child-bearing age, how to balance the maternal risk and patients’ reproductive rights remains understudied and under-recognised.

Hypothesis:
We assessed the hypothesis that if the mild CHD-PH patients have better pre-pregnancy cardiac situation, their pregnancies shouldn’t all be contraindicated.

Methods:
Patients were retrospectively included before March 2017 and 205 cases were prospectively collected after that time. Pregnancy with CHD-PH was subdivided into two subgroups based on the estimated SPAP measured by non-invasive echocardiography (30-50 mmHg as mild and >50 mmHg as moderate-to-severe).

Results:
Of 2220 completed pregnancies with CHD from 7 tertiary institutions, 729 women had CHD-PH (398 mild CHD-PH). Of PH patients, the main CHD diagnosis is shunt lesion (70.92%) and only 26.89% were surgically repaired. The mortality and incidence of heart failure were 2.60% and 21.81%, respectively. No dead case happened in mild CHD-PH. Independent risk factors of maternal cardiac events included brain natriuretic peptide level, NYHA class, ejection fraction (EF), unrepaired CHD, strict supervision, late antenatal visit, without MDT and the severity of PH(except for mild CHD-PH). Furthermore, after propensity score matching analysis, the no-PH and mild PH groups have no significant difference in the maternal and offspring outcomes. Consistency Analysis indicated that mild CHD-PH had lower cardiac incidence than level IV of the modified WHO, except when they were associated with NYHA III-IV or EF<50%.

Conclusion:
To conclude, pregnancy in women with CHD-PH continues to be associated with significant morbidity, although their mortality is relatively low. If the mild CHD-PH patients have better pre-pregnancy cardiac situation (EF>50% and NYHA I-II), their pregnancies shouldn’t all be contraindicated.
Abstract 12296: Clinical and Functional Genetic Characterization of the Role of Cardiac Calcium Channel Variants in the Early Repolarization Syndrome
Authors: Barajas-martinez Hector , Antzelevitch Charles N , Hu Dan
Published: April 2022

Introduction:
Early repolarization syndrome (ERS) is an inherited sudden cardiac death syndrome.

Hypothesis:
In this study we test the role of genetic variants in cardiac calcium channel genes in the pathogenesis of ERS and probes the underlying mechanisms.

Methods:
PCR-based next-generation sequencing was carried out using a targeted gene approach. Unrelated ERS probands carrying calcium channel variants were evaluated clinically and compared with matched healthy controls. Wild type (WT) and mutant
CACNA1C
genes were co-expressed with
CACNB2b
and
CACNA2D1
in HEK293 cells and studied using whole-cell patch-clamp and confocal fluorescence microscope
.

Results:
Among 104 ERS probands, 16 carried pathogenic variants in calcium channel genes (32.2±14.6 years old, 87.5% male). The symptoms at diagnosis included syncope (56.3%), ventricular tachycardia/fibrillation (VT/VF, 62.5%), sudden cardiac death (SCD, 56.3%). Three cases (18.8%) had a family history of SCD or syncope. Eight patients (50.0%) had a single calcium gene rare variant. The other half carried rare variants in other ERS susceptible genes. Compared with controls, the heart rate was slower (72.7±8.9 vs. 65.6±16.1 bpm), QTc interval was shorter (408.2±21.4 vs. 386.8±16.9 ms) and Tp-e/QT was longer (0.22±0.05 vs.0.28±0.04) in calcium mutation carriers. Electrophysiological analysis of one mutation,
CACNA1C
-P817S revealed that the density of I
Ca
was reduced by approximately 84.6% compared to WT (-3.1±2.5 vs. -20.5±3.6 pA/pF, n=11 and 15, respectively). Heterozygous expression of mutant channels was associated with a 51.3% reduction of I
Ca
. Steady-state inactivation was shifted to more negative potentials and significantly accelerated. Confocal microscopy revealed trafficking impairment of
CACNA1C
-P817S (peripheral/central intensity: 0.94±0.1 in WT vs. 0.33±0.1 in P817S, n=10 and 9, respectively).

Conclusions:
ERS associated with loss of function (LOF) genetic defects in genes encoding the cardiac calcium channel represents a unique clinical entity characterized by decreased heart rate and QTc, as well as increased transmural dispersion of repolarization. In the case of
CACNA1C
-P817S impaired trafficking of the channel to the membrane contributes to the LOF.
Abstract 12505: Clinical Characteristics of Patients With Vasospastic Angina Subjected to the Spasm Provocation Test Involving the Unavoidable Use of Nitroglycerin
Authors: Teragawa Hiroki , Orita Yuichi , Oshita Chikage , Akazawa Ryota , Uchimura Yuko
Published: April 2022

Introduction:
Multivessel spasm (MVS) has a prognostic impact in patients with vasospastic angina (VSA). Thus, assessing for the presence of MVS in both left coronary artery and right coronary artery is preferable in the spasm provocation test (SPT). The use of nitroglycerin is necessary to avoid the complications related to SPT; however, this unavoidable use of NTG (U-NTG) may decrease the detection of MVS.

Hypothesis:
We investigated the frequency of U-NTG during SPT and clarified the clinical characteristics in VSA patients, with U-NTG during STP.

Methods:
Total 142 patients with positive SPT were evaluated. A positive SPT was defined as >90% constriction in coronary arteries, accompanied by the chest symptoms and/or ischemic ST-T changes. When a coronary spasm occurred, we usually waited for the spontaneous relief of the coronary spasm. However, if a prolonged coronary spasm or unstable hemodynamics occurred, NTG was administered to relieve the coronary spasm promptly (U-NTG). Even when U-NTG was administered in one coronary artery, an additional SPT was performed on another coronary artery. The patients were divided into two groups according to U-NTG: U-NTG(+) (n = 42) and U-NTG(-), (n = 100). The clinical characteristics and frequencies of MVS and complications (unstable hemodynamics) during the SPT were compared between the groups.

Results:
Except for smoking status, all other clinical characteristics status did not differ significantly between the groups. More current smokers were observed in the U-NTG(+) group (29%) compared with that in the U-NTG(-) group (12%, p = 0.03). The frequency of MVD did not vary significantly between the groups, with 64% in the U-NTG(+) and 52% in the U-NTG(-). No significant difference was found between the groups in the frequency of severe complications during SPT, with 5% in U-NTG(+) and 3% in U-NTG(-). In U-NTG(+), the positive induction of coronary spasm in another coronary artery was 40% (17/42).

Conclusions:
Our results show that U-NTG occurred in ~30% of VSA patients, especially in current smokers, and that it did not decrease the detection of MVS and prevented severe complications during SPT. Therefore, U-NTG is acceptable during SPT, after which, another test may be performed to assess the presence of MVS.