bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12017: Correlates of Regional Diastolic Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Frljak Sabina , Poglajen Gregor , Zorz Neza , Cerar Andraz , Zemljic Gregor , Vrtovec Bojan
Published: April 2022

Introduction:
The underlying mechanisms of regional myocardial dysfunction in patients with heart failure with preserved ejection fraction (HFpEF) remain poorly defined.

Hypothesis:
We investigated physiological correlates of regional diastolic dysfunction in HFpEF using a novel technique based on point-by-point measurement of local diastolic delay.

Methods:
We enrolled 30 patients with HFpEF (LVEF >50%, E/e' >15, NT-proBNP >300 pg/ml). In all patients we performed electroanatomical mapping of the left ventricle and assessed regional diastolic function by a novel algorithm based on the measurement of local diastolic delay. Local diastolic delay was considered significant if the time delay between global left ventricular end diastolic time and local diastolic time was >50 msec. At the time of mapping, we performed clinical evaluation, echocardiography and measured plasma levels of 27 biomarkers of angiogenesis and endothelial dysfunction.

Results:
Our cohort included 23 male and 7 female patients, aged 46-70 years. Using electroanatomical mapping we measured regional diastolic function in 4820 mapping points. The mean local diastolic delay was >50 msec in 12 patients (Group A), and <50 msec in 18 patients (Group B). The groups did not differ in age (64±11 years in Group A vs. 51±8 years in Group B, P=0.22), gender, (male: 83% vs. 73%, P=0.48), creatinine (1.08±0.31 mg/dL vs. 1.10±0.30 mg/dL, P=0.52), LVEF (56±4% vs. 58±7%, P=0.42), or NT-proBNP levels (1570±1310 pg/mL vs. 1230±1240 pg/mL, P=0.22). However, in Group A, we found higher values of E/e’ (18.2±3.4 vs. 17.0±2.8 in Group B, P=0.04), and lower myocardial viability (unipolar voltage: 7.73±1.8 mV vs. 9.03±2.1 mV, P=0.02). When compared to Group B, patients in Group A displayed lower levels of pro-angiogenic biomarkers (vascular endothelial growth factor: 33±22 pg/mL vs. 47±24 pg/mL, P=0.01; platelet-derived growth factor: 47±23 pg/mL vs. 78±34 pg/mL, P=0.02), and higher levels of anti-angiogenic biomarkers (agiopoietin-2: 7.0±3.8 ng/mL vs. 2.7±1.0 ng/mL, P=0.01; endostatin: 87±33 ng/mL vs. 65±21 ng/mL, P=0.02).

Conclusion:
In patients with HFpEF, regional diastolic dysfunction appears to be associated with increased E/e’, decreased myocardial viability, and impaired angiogenesis.
Abstract 12019: Muscular Microcirculatory Dynamics During Lower Limb Strength Exercise Testing in Heart Failure With Preserved Ejection Fraction
Authors: Vale-Lira Amanda , Turri-Silva Natalia , Verboven Kenneth , Quagliotti Durigan JOAO LUIZ , Hansen Dominique , Cipriano Gerson
Published: April 2022

Introduction:
Muscular microcirculatory dynamic changes during muscle strength effort remain to be studied in different heart failure (HF) phenotypes and severities. This study compare the muscular microcirculatory responses during strength exercise testing in HF with preserved ejection fraction (HFpEF) with reduced ejection fraction (HFrEF) and disease severities.

Hypothesis:
HFpEF patients display worse microvascular function during strength exercise testing, particularly in those with more severe disease (according to Weber classification).

Methods:
Seventeen HF patients (HFpEF, n=10, HFrEF n=7, mean age 57±6 years) underwent muscular microcirculatory dynamics assessment by near-infrared spectroscopy (tissue saturation index, TSI, %; oxyhemoglobin, O
2
Hb, μM and deoxyhemoglobin concentration, HHb, μM) during concentric isokinetic strength exercise testing (20 repetitions at an angular velocity of 180°/s) and subsequent recovery. Patients were analyzed according to their phenotype and disease severity (Weber A+B and Weber C).

Results:
From HFpEF, Weber Class C patients presented a poor capability to achieve higher oxygen extraction during exercise than Class A and B. Among those with Weber C, while HFrEF patients presented lower oxyhemoglobin (O
2
Hb, μM) (-18.9±11.8 vs.-8.9±5.6, p=0.029) during exercise, HFpEF had lower O
2
Hb during the recovery period (-3.0±3.4 vs. 5.9±2.8, p=0.007). Figure 1 illustrates muscular oxygenation dynamics in heart failure phenotypes and severities. No differences for TSI and HHb, neither on O
2
Hb in between phenotypes on Weber A+B severity.

Conclusions:
Preliminary findings regarding muscular microcirculatory oxygen reduction during isokinetic muscle strength testing are present in HFpEF patients more severely impaired (Weber C), which helps explain exercise intolerance in Heart Failure, reinforcing a worst circulatory periphery environment in such phenotype.
Abstract 12027: Low-Density Lipoprotein Cholesterol in Patients With Homozygous Familial Hypercholesterolemia Who Participated in Sequential Studies of Alirocumab and Evinacumab
Authors: Raal Frederick J , Rosenson Robert S , Kolovou Genovefa , Harada-shiba Mariko , Mitchenko Olena , Rubba Paolo , ali shazia , Banerjee Poulabi , Khilla Nagwa , McGinniss Jennifer , pordy robert , Blom Dirk J
Published: April 2022

Background:
Homozygous familial hypercholesterolemia (HoFH) is characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. This analysis evaluated LDL-C changes in patients with HoFH who sequentially participated in interventional trials with alirocumab (NCT03156621) and evinacumab (NCT03399786).

Methods:
A total of 25 patients completed the alirocumab trial and entered the evinacumab trial and were randomized to intravenous evinacumab 15 mg/kg (n=16) or placebo (n=9) every 4 weeks. The primary outcome for the evinacumab trial was percent change in LDL-C from baseline to week 24.

Results:
Baseline characteristics were generally well balanced. Among patients who participated in the alirocumab trial, a reduction in LDL-C of –44.6% and –1.1% was observed at week 24 in patients treated with evinacumab versus placebo, respectively. Overall, mean total reductions in LDL-C (Figure) and apolipoprotein B of -62.9% and -54.9%, respectively, were observed in patients treated with the combination of alirocumab and evinacumab; and triglycerides were lowered by -54.5%. The absolute LDL-C reduction from their baseline in patients treated with the combination of alirocumab and evinacumab was -216.3 mg/dL. No new safety signals were observed when treated with alirocumab and evinacumab, and were consistent with the respective trial results.

Conclusions:
Combination therapy with alirocumab and evinacumab reduced LDL-C by more than 60% in patients with HoFH and was well tolerated.
Abstract 12036: Decreased Sympathetic Innervation Around the Left Atrium After Multiple Catheter Ablation Procedures for Atrial Fibrillation
Authors: Fukunaga Hiroshi , Iguchi Nobuo , Kasai Yuhei , Asano Sou , Nagase Takahiko , Sekiguchi Yukio , TANIZAKI KOHEI , Nitta Junichi , Isobe Mitsuaki
Published: April 2022

Introduction:
Cardiac sympathetic activity is involved in the initiation and maintenance of atrial fibrillation. A novel technique that evaluates the atrial accumulation of 123I-MIBG may be able to assess the atrial sympathetic innervation. The purpose of this study was to visually evaluate the modification of sympathetic innervation caused by multiple catheter ablations.

Methods:
The total study cohort comprised 32 patients with atrial fibrillation. 21 patients underwent only one ablation using a balloon catheter (cryoballoon in 10 patients; hot balloon in 11 patients) (group 1), while 11 patients underwent multiple radiofrequency catheter ablation procedures (three procedures in 6 patients; four procedures in 5 patients) (group 2). In all patients, the left atrial sympathetic activity was evaluated using MIBG images obtained using a novel solid-state whole-body scanner (VERITON). For local quantitative evaluation, the site with the strongest discrete MIBG accumulation was automatically recognized by the computer and compared in pre- and post-procedural images.

Results:
In all patients, the total left atrial MIBG accumulation value after ablation (6.64х10
4
±1.65х10
4
PROPCNTS) was significantly lower than that before ablation (7.74х10
4
±2.25х10
4
PROPCNTS, p=0.0289). At the site with the strongest discrete MIBG accumulation, the MIBG accumulation after ablation was decreased in 19 patients, unchanged in 9, increased in 3, and shifted in 1. The total left atrial MIBG accumulation value before ablation was significantly lower in group 2 (5.74х10
4
±1.40х10
4
PROPCNTS) than group 1 (6.67х10
4
±1.57х10
4
PROPCNTS, p=0.0485).

Conclusions:
The MIBG accumulation in the left atrium decreased after catheter ablation. Furthermore, preoperative evaluation revealed a significant decrease in MIBG accumulation after multiple ablation procedures. This suggests that multiple catheter ablation of the left atrium modifies the sympathetic innervation.
Abstract 12074: Rhythm Control Strategy in Recent Atrial Fibrillation: An Online Educational Intervention Improved Physician Knowledge, Competence, and Confidence
Authors: Harris Margaret , Amara Walid , Chang Lih-Fan , Lacouture Michael , Guedj Philippe
Published: April 2022

Background:
In clinical practice, rhythm control strategies, including antiarrhythmic drugs (AAD), are currently used for the management of patients with arrhythmias. Despite latest guideline updates and randomized trials on early rhythm control strategies, physicians remain uncertain on the selection of a good strategy for these patients.

Purpose:
To determine if an online continuing medical education intervention could improve knowledge, competence, and confidence of cardiologists and surgeons related to latest data on rhythm control strategies and the use of AAD in patients with recent AF.

Methods:
Cardiologists and surgeons electively participated in a video-based, 3-faculty educational panel discussion on earlier rhythm control strategies in recent AF. A repeated pairs pre-/post-assessment study design was used and a paired samples t-test for overall and McNemar’s test at the question level (
P
<.05 is considered significant) assessed statistical significance. Data were collected March 3, 2021 through June 1, 2021.

Results:
Overall significant improvements were seen after education for both cardiologists (N = 525) and surgeons (N = 2180). Pre-assessment, the average correct response rate was 55% for cardiologists and 51% for surgeons, while post-assessment average correct response rates increased to 66% and 64%, respectively. Significant improvements were observed in cardiologists’ and surgeons’ knowledge and competence related to the use of rhythm control strategies in recent AF (Table). As a result of the education, 39% of cardiologists and 48% of surgeons had a measurable improvement in their confidence on rhythm control strategies choice in recent AF.

Conclusion:
The statistically significant improvements observed in this intervention demonstrate that participation in a video-based panel discussion to increase knowledge, competence, and confidence of cardiologists regarding the selection of rhythm control strategies in recent AF.
Abstract 12075: Utility of Cardiac MRI for Assessment of Patients with Myocardial Infarction and Non-Obstructive Coronary Arteries: 5-Year Experience in a Tertiary Care Center in Latin-America
Authors: Higuera Sergio A , Perez-Fernandez Oscar M , Forero Julian , Jaimes Claudia , Isaza Daniel , Medina Hector
Published: April 2022

Introduction:
Acute myocardial infarction with non-obstructive coronary arteries (MINOCA) is a frequent condition caused by a wide array of diseases. Absence of a definitive diagnosis can difficult proper treatment and may worsen prognosis. Given its unique ability to achieve tissue characterization, cardiac magnetic resonance (CMR) can be extremely useful in these patients. We sought to describe the use of CMR in a tertiary care center in Latin-America for the evaluation of MINOCA and its impact in patient management.

Methods:
Cross-sectional study of all hospitalized patients with MINOCA undergoing CMR and impact in medical management at discharge based on its result.

Results:
A total of 3283 patients underwent CMR between 2016 and 2020 in our institution. Of these, 144 had MINOCA (without IVUS/OCT imaging) as the main indication for the study. Mean age was 50.7 ± 14.8 years and 56.9% were females. The most frequent diagnosis after CMR was myocarditis in 50% of cases (n=71) followed by AMI in 22% (n=31) and Tako-Tsubo Syndrome in 12% (n=17). Only 11% (n=15) of CMR were normal (Fig 1). There were significant changes in prescription before and after CMR of ASA, dual-antiplatelet therapy (DAPT), anticoagulants (AC), betablockers (BB), statins, colchicine and NSAIDs (Fig 2).

Conclusions:
CMR is critical for making a definitive diagnosis in a substantial proportion of MINOCA patients and its use has a significant impact in medical regimen optimization at discharge. Figure 1. Definite diagnosis achieved after CMR. AMI: Acute Myocardial Infarction. CMP: Cardiomyopathies. HCM: Hypertrophic Cardiomyopathy. TS: Takotsubo Syndrome.Figure 2. Changes in prescription before and after CMR.
Abstract 12107: Increased Prehospital Aspirin Use for Myocardial Infarction Patients With Atypical Symptoms Could Reduce Mortality
Authors: Moeller Amalie L , Rytgaard Helene C , Mills Elisabeth H , Christensen Helle C , Blomberg Stig N , Folke Fredrik , Kragholm Kristian H , Gislason Gunnar H , Torp-Pedersen Christian
Published: April 2022

Introduction:
Myocardial infarction (MI) patients with atypical symptoms receive poor prehospital management and have high mortality. We studied the importance of emergency ambulance response and prehospital aspirin use for survival of these patients.

Methods:
In Copenhagen, Denmark, citizens can call a 24-h non-urgent medical helpline or an emergency number 1-1-2 (equivalent to 9-1-1) for medical assistance. The primary symptom/purpose of calls is registered at both services. We included calls regarding patients hospitalized with an MI up to 24 h after the call and categorized calls according to primary symptom of chest pain or atypical symptom. Mediation analysis was used to examine the effect of modifying prehospital management.

Results:
We identified 5,440 calls regarding MI patients, 4,127 (76%) with chest pain and 1,313 (24%) with atypical symptoms. Compared to MI patients with chest pain, patients with atypical symptoms were older (median 73 vs 67 years), more often female (44% vs 31%), and had more often called the medical helpline (46% vs 32%).

Among MI patients, 30-day mortality was 2.8% for chest pain and 10.9% for atypical symptoms. In the mediation analysis, mortality increased slightly to 11.3%, an increase of 0.3% CI95% [-1.2%; 1.8%], when changing the probability of receiving emergency ambulances for MI patients with atypical symptoms to the probability for chest pain patients. Emergency ambulances were dispatched to 4.277 (79%) of the MI patients. Among these, 30-day mortality was 2.9% for patients with chest pain and 13.1% for atypical symptoms. Changing the probability of receiving aspirin for patients with atypical symptoms to the probability for patients with chest pain decreased mortality to 10.5%. A reduction of -2.6% CI95% [-5.1%; -0.1%].

Conclusion:
MI patients presenting with atypical symptoms have high mortality. Results from the mediation analysis suggest that increased prehospital use of aspirin could improve survival for these patients.
Abstract 12110: Low Density Lipoprotein Receptor-Related Protein 1 Levels and Syntax Score in Patients Presenting With ST Elevation Myocardial Infarction
Authors: Agirbasli Mehmet A , bolen furkan , Korkmaz Rabia , Kartal Ilkay , isman ferruh K
Published: April 2022

Introduction:
Low density lipoprotein receptor-related protein 1 (LRP1) protects against cardiomyocyte death through its ability to promote Akt- and ERK1/2-dependent survival pathways. LRP1 signaling is crucial in promoting cell survival. LRP1 inhibits cell death, and promotes the resolution of the inflammation and scar formation following tissue injury. LRP1 serves as a common receptor that mediates the myocardial cell protective effects of several signaling cascades. The association between LRP1 and severity coronary artery disease (CAD) in the setting of acute injury, such as ST elevation myocardial infarction (STEMI) remains to be elucidated. We measured the soluble LRP1 (sLRP1) levels in patients who presented with STEMI. CAD severity as assessed by SYNTAX score.

Methods:
We measured sLRP1 levels in 46 patients who presented with STEMI (mean age 61±13.3, M/F=36/10). The SYNTAX score was categorized as low (≤20), and high (>20). The control group (n=60) was selected from outpatients without significant comorbidities (N=60, age 47±14.2, M/F=16/44).

Results:
Patients with STEMI and high SYNTAX scores display significantly lower sLRP1 levels compared to the group with STEMI and low syntax score and controls (p=0.035 and 0.016, respectively). Median (IQR) sLRP1 levels are 1.90 (0.67), 2.25 (2.56) and 2.26 (1.59) μg/ml, respectively (Figure 1).

Conclusions:
Previous studies indicate that LRP1 is cardioprotective by the activation of the reperfusion injury salvage kinase pathway after ischemia reperfusion. In this study we observe that sLRP1 decreases with the complexity of CAD in patients with STEMI. Low sLRP1 levels can be a biomarker of complex CAD. Various studies have reported the role of LRP1 in cardiac remodeling after myocardial injury. Future studies are required to estimate the utility of sLRP1 as a diagnostic and prognostic biomarker in STEMI. This work was supported by the Research Fund of Istanbul Medeniyet University (project number 1358).
Abstract 12124: A Composite Score Summarizing Use and Dosing of Evidence-Based Medical Therapies in Heart Failure: A Nationwide Cohort Study
Authors: Johansen Niklas , Vaduganathan Muthiah , Zahir Deewa , Fiuzat Mona , Defilippis Ersilia M , Januzzi James L , Butler Javed , O'Connor Christopher , Abraham William T , Psotka Mitchell , McMurray John J , Jensen Jens-Ulrik Staehr , Schou Morten , Torp-Pedersen Christian , Kober Lars , Gislason Gunnar H , Biering-Sørensen Tor
Published: April 2022

Introduction:
As heart failure (HF) therapeutic care becomes increasingly complex, determining optimal medical therapy (OMT) can be challenging. The HF Collaboratory consortium developed a scoring system to assist with standardization of comparing OMT within and across trials. We evaluated the score in the Danish HF population.

Methods:
In a retrospective nationwide cohort study, we identified all Danish HF patients alive on July 1, 2018. Patients were excluded if they were diagnosed after July 1, 2017 to allow a minimum of 365 days for up-titration of medical therapy. Treatment doses were estimated by analysis of consecutive claimed prescriptions. An integer-based composite medical therapy score (range 0-10) was designed to consider use and dosing of multiple therapies prescribed to each patient (
Panel A
). Risk-adjusted association was assessed between the composite score and subsequent death.

Results:
In total, 26,779 patients (median age 73y; 32% women) were identified. At baseline, ACEi/ARB was used in 77%, β-blocker in 81%, MRA in 30%, ARNi in 2%, SGLT2i in 2%, and ivabradine in 2%. The median composite medical therapy score was 4 (and was consistently 4 from January 2016-July 2018). During median follow-up of 1.5 years, 3,326 deaths occurred. After accounting for demographics, comorbidities, loop diuretic use, HF diagnosis setting, and time since HF diagnosis, higher composite scores were independently associated with lower mortality (≥median vs <median: aHR 0.73 [0.67-0.78]; p<0.001). In restricted cubic spline analysis based on a fully adjusted Poisson regression model, a graded, inverse association between the score and death was observed; p<0.001 (
Panel B
).

Conclusions:
Nationwide assessment of therapeutic optimization in HF using a composite medical therapy score was feasible and the score was independently associated with survival. These data suggest that most patients can achieve a score of 4 or more in current clinical care.
Abstract 12129: Vascular Endothelial Barrier Protection May Prevent Arrhythmias in Atrial Fibrillation and Myocardial Infarction
Authors: Mezache Louisa , Nuovo Gerard , Veeraraghavan Rengasayee
Published: April 2022

Vascular leak is a major sequela of inflammation, which is associated with arrhythmic pathologies such as atrial fibrillation (AF) and myocardial infarction (MI). We recently demonstrated that the vascular leak-inducing cytokine vascular endothelial growth factor (VEGF; 90-580 pg/ml - levels found in AF patients) induces acute remodeling (30-60 minutes) of sodium channel (Na
V
1.5) -rich intercalated disk (ID) nanodomains, disrupting their ultrastructure and prompting translocation of Na
V
1.5 from these sites. This in turn disrupted impulse propagation and promoted arrhythmias in murine atria. Here, we tested the hypotheses that i) similar acute pro-arrhythmic remodeling occurs in the ventricles of MI patients, and ii) protecting the vascular barrier may prevent arrhythmias following an acute inflammatory insult. First, we examined myocardial samples from five human MI patients. VEGF was overexpressed in both cardiomyocytes and vascular endothelium in the border zone surrounding <6 month-old infarcts. Notably, co-localization analysis showed significantly reduced Na
V
1.5 near both connexin43 and N-cadherin within the border zone in 1-, 3-, and 9-day-old infarcts, paralleling our observations in mouse atria. Next, we returned to our murine model of AF induced by acute inflammatory insult (100 pg/ml VEGF for 60 minutes) to test the antiarrhythmic efficacy of protecting the vascular endothelial barrier. Overall, median
in vivo
arrhythmia burden was higher in VEGF-treated mice relative to vehicle controls (7.5±11 vs. 0±6 s/hr). We tested two strategies shown to prevent vascular barrier breakdown: Blocking connexin43 hemichannels (αCT11 peptide) decreased
in vivo
arrhythmia burden to 0 ± 6.07 s/hr. Panx1-IL2 (a peptide inhibitor of Panx1 channels) treatment decreased also
in vivo
arrhythmia burden (0 ± 15.57 s/hr with 1.6 μM Panx1-IL2). Similar antiarrhythmic efficacy was also achieved with small molecule inhibitors of Cx43 and Panx1. These results highlight VEGF-induced vascular leak as a novel mechanism for acute arrhythmias both in the early stage AF and following MI. Indeed, this mechanism may contribute to post-MI AF. Importantly, vascular-barrier protection may be a viable strategy to prevent these arrhythmias.
Abstract 12137: Common Metabolic Determinants of Cardiac and Pulmonary Function in the General Population
Authors: Ghosh Nilanjana , Wibom Sandra , Czuba Tomasz , Landenhed Smith Maya l , Engstrom Gunnar , Smith Gustav
Published: April 2022

Background:
Heart failure is associated with a restrictive spirometry pattern, but limited data is available on the relation of subclinical measures of pulmonary function to cardiac function. We sought to explore such associations in a population-based cohort study as well as metabolic factors commonly associated with such measures.

Methods:
Participants of the population-based Swedish cohort study SCAPIS-Malmö (age 50-64) underwent spirometry (n=6251), of which random subsets also underwent echocardiograpy (n=1885) and untargeted plasma metabolite profiling (n=3,986). The association of spirometric (FEV1, FVC, DLCO) and echocardiographic parameters (E/E', stroke volume [SV], systolic pulmonary arterial pressure [sPAP]) were examined using multivariable-adjusted regression models and cubic spline functions.Metabolites were tested for association with spirometric and echocardiographic parameters with adjustment for age, sex, bmi, smoking, eGFR, diabetes, hypertension, COPD, asthma, and heart failure.

Results:
After adjustment for smoking and other established risk factors, lower FEV1, FVC and DLCO remained associated with higher E/E', sPAP, and lower SV (p<0.001). Spline analyses were consistent with linear effects. Profiling of 1318 metabolites identified associations with lower FEV1, FVC, DLCO and higher E/E' for lower levels of 6 correlated lipid molecules including plasmalogens, lysophospholipids and a phosphatidylcholine, all of which also correlated with the main constituent of pulmonary surfactant (dipalmitoylphosphatidylcholine), and with higher levels of an amino acid and its deaminated product. Lower levels of bilirubin were associated with lower FEV1, FVC, DLCO, and lower SV.

Discussion:
In this contemporary, middle-aged cohort with low prevalence of manifest cardiac or pulmonary disease we observed associations between lower lung volumes and CO diffusion capacity with restrictive cardiac filling. Furthermore, our findings nominate metabolic factors that associate with both cardiac and pulmonary function, suggestive of shared pathophysiological processes.
Abstract 12142: Intravascular Ultrasound Guided Percutaneous Coronary Intervention Improves Acute Angiographic Results & 1-year Clinical Outcomes for Patients With Chronic Total Occlusion
Authors: BI Jiachen , Hau Kongto , Yan Bryan P
Published: April 2022

Introduction:
Intravascular ultrasound (IVUS) on long-term clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is not well established. This study aimed to evaluate IVUS-guided compared to angiography-only-guided CTO-PCI on acute angiographic result and 1-year clinical outcomes.

Hypothesis:
The application of IVUS in CTO-PCI could improve acute angiographic results and 1-year clinical outcomes for all-comers CTO patients.

Methods:
We analysed 528 consecutive patients undergoing CTO-PCI at a university affiliated hospital in Hong Kong from February 2009 to December 2016. Baseline characteristics, procedural characteristics, and 1-year clinical outcomes including cardiac death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), and composite target lesion failure (TLF) were evaluated. The use of IVUS, and the choice of PCI devices including plain old balloon angioplasty (POBA), bare metal stent (BMS), and drug eluting stent (DES), were at the discretion of the operator. Propensity score matching (PSM) was performed to reduce treatment selection bias and potential confounding factors.

Results:
275 patients underwent 288 angiography-only-guided and 253 patients underwent 268 IVUS-guided CTO-PCI. IVUS-guided CTO-PCI was associated with higher procedural success compared to angiography-only-guided CTO-PCI (77.5% vs. 55.3%, p<0.01). DES were used more often in the IVUS-guided CTO-PCI group (85.3% vs. 65.6%, p<0.01) while BMS were used less in IVUS-guided CTO-PCI group (9.3% vs. 26.1%). After PSM for successful CTO stented patients, angiography-IVUS guidance was associated with more post stent balloon dilatation (84.7% vs. 56.3%, p<0.01), lower incidence of >20% residual stenosis (2.2% vs. 10.8%, p<0.01), longer total stent length (44.16±23.88mm vs. 33.52±18.90mm, p<0.01), and larger final angiographic stented diameter (3.12±0.63mm vs. 2.94±0.48mm, p<0.01). IVUS guided CTO-PCI was associated with lower 1-year TLF rates (3.0% vs. 10.0%, p=0.01).

Conclusions:
The use of IVUS was associated with higher success rates, more aggressive post-dilatation and better 1-year clinical outcomes compared to angiography-only guided CTO-PCI.
Abstract 12144: Prognostic Value of Preoperative Cardiac Troponin I and T in Patients With Acute Coronary Syndromes Undergoing Coronary Artery Bypass Grafting: A Current Report of the North-Rhine-Westphalia Surgical Myocardial Infarction Registry
Authors: Thielmann Matthias , Priebe Lucas , WENDT Daniel , Shehada Sharaf-Eldin , Osswald Anja K , Zubarevich Alina , Schmack Bastian , Weymann Alexander , Wahlers Thorsten , Choi Yeong Hoon , Ruhparwar Arjang , Liakopoulos Oliver J
Published: April 2022

Introduction:
The extent of myocardial injury is a major determinant of morbidity and mortality in patients undergoing coronary artery bypass grafting (CABG) with acute coronary syndromes (ACS). More recently, cardiac biomarkers such as troponin I and T have been suggested as predictors for unfavorable outcome. We aimed to evaluate the predictive value of cardiac troponin (I and T) on a multicentric basis.

Methods:
We obtained multicentric data from a national surgical myocardial infarction registry with 2432 patients undergoing CABG with ACS between 01/2010 and 12/2018. Primary study endpoint was all-cause, in-hospital mortality (IHM) and postoperative major adverse cardiac and cerebrovascular events (MACCE). Multivariable logistic regression models and receiver-operating curve (ROC) analyses were applied to assess predictive value of preoperative cTnI and T for IHM and MACCE following CABG.

Results:
Patients were 68±11years of age, 78% male, 24.5% had unstable angina (UAP), 50.0% NSTEMI, and 25.4% STEMI, presenting a logEuroSCORE-I of 15.1±15.1% in UAP, 20.3±20.1% in NSTEMI and 23.5±20.0% in STEMI. Preoperative cTnI or T was obtained on admission and preoperatively with 5.4±19.5 and 3.6±10.0ng/mL for cTnI and 0.93±1.7 and 0.90±1.8ng/mL for cTnT. Preoperative cTnI and T was significantly increased between survivors and non-survivors (cTnI:4.2±11.9 vs. 22.4±59.5ng/mL,
P
<0.05 and cTnT:0.9±1.7 vs. 1.3±1.9ng/mL;
P
<0.05). STEMI patients demonstrated higher cardiac biomarker levels and worse IHM (12.6%) compared to NSTEMI (7.3%;
P
<0.01) and UAP patients (4.2%;
P
<0.01). Multivariable logistic regression analysis revealed cTnI but not cTnT to be a strong and independent predictor for IHM and MACCE (
P
<0.001). Preoperative cTnI and T >2xURL showed a significant predictive value for IHM (
P
<0.003) and MACCE (
P
<0.001). In a ROC analysis, a cTnI value of 10.1ng/mL with an area under curve (AUC) of 0.65 (
P<
0.01) was identified as an optimal cut-off value for IHM and 6.8ng/mL with an AUC of 0.65 (
P
<0.001) for MACCE.

Conclusions:
In this large-scaled national registry, we can confirm that preoperative cardiac troponin I but not T indicates important prognostic information of in-hospital mortality and MACCE rate in ACS patients undergoing CABG surgery.
Abstract 12159: Impact of Ischemic Heart Disease on Cardiac Resynchronization Therapy - Analysis From National Inpatient Sample
Authors: Balian Steve , Balian Steve , Khan Waqas , Hassan Jawad , Minhas Abdul , Bailey Beth , Baloch Zulfiqar Qutrio , Banga Sandeep , Abela george
Published: April 2022

Introduction:
Comparative outcomes of hospitalizations for Cardiac Resynchronization Therapy (CRT) implantation procedures with and without coexisting Ischemic Heart Diseases (IHD) have not been studied at national level databases. We attempted to assess outcomes and baseline characteristics in these hospitalizations based on the National Inpatient Sample (NIS).

Hypothesis:
Ischemic heart disease worsens inpatient outcomes in patients undergoing CRT implantation.

Methods:
We conducted a retrospective analysis of hospitalizations for CRT implantation from the National Inpatient Sample (NIS) between 2013 and 2014. ICD-9 Billing codes were used to identify the target population. The primary outcomes were inpatient mortality, and hospital length and cost of stay.

Results:
A total of 11057 cases were identified. IHD was listed as any diagnosis in 66% of these hospitalizations. The mean age was 72.5 and 66.9 years for CRT implantation with and without IHD, respectively. Hospitalizations without IHD were more likely to be female (44% vs. 25%; p=0.01). Patients in the CRT with IHD group had a higher comorbidity burden with a higher proportion of hypertension, chronic kidney disease, anemia, peripheral artery disease, and congestive heart failure (Table 1). Inpatient mortality was similar between both groups (OR 1.17, CI 0.75-1.81). The IHD cohort had higher rates of cardiac arrest (OR 1.30, CI 1.05-1.62), acute kidney injury (OR 1.21, CI 1.08-1.35), longer length and a higher cost of stay (Table 1).

Conclusions:
IHD is associated with higher costs, longer length of stay, and higher rates of cardiac arrest. However, the in-hospital mortality was not different between the two groups. Higher incidence of cardiac arrest in patients with CRT and IHD underlines the importance of ICD with CRT. The clinical implication is that the threshold of selecting a CRT-D device in patients eligible for CRT therapy should be lower in patients with IHD vis-à-vis patients without IHD.
Abstract 12172: Relationship Between Increased QTc Risk Score and In-Hospital Mortality
Authors: Tisdale James E , Tan Malinda , Heise C. W , Gallo Tyler , Woosley Raymond L , Antonescu Corneliu , Gephart Sheila , Malone Daniel
Published: April 2022

Introduction:
Torsades de pointes (TdP) is a life-threatening arrhythmia associated with prolongation of the heart rate-corrected QT (QTc) interval. QTc prolongation is associated with increased mortality. A QTc Risk Score (QTc-RS) advisory has been developed, but the ability of the QTc-RS to predict mortality is unknown.

Objective:
To evaluate the relationship between a validated QTc-RS and mortality among hospitalized patients.

Methods:
An advisory incorporating a previously validated QTc-RS was implemented as a clinical decision support tool at 28 inpatient facilities. When an order was initiated for a known QTc-prolonging medication, a QTc-RS (maximum score = 21) was electronically calculated and, if the score was > 11, prescribers received a warning that included patient-specific risk factors. The advisory also provided single click actions for laboratory tests, electrocardiogram orders, cancelling incoming medication orders or discontinuing existing QTc-prolonging medications.

Results:
Between April and November 2020, there were 144,148 QTc-RS scores calculated. Among the 7923 warnings with a score >11, the majority (51%) had a score of 12, 29% had a score of 13, 12% had a score of 14, and 8% had a score ≥ 15. The most common risk factors were: age > 67 years (66%); sepsis (65%); ≥ 1 QTc-prolonging medication(s) (60%); female (59%); heart failure (34%); serum potassium < 3.5 mEq/L (28%); and a loop diuretic (21%). Among those with a QTc-RS >11, 11.9% (944/7923) expired during the inpatient encounter. The proportion of deaths increased as the risk score increased (Table 1). Relative to individuals with QTc-RS 12-14, the odds ratio for inpatient mortality in those with scores >17 was 3.0 (95% CI:1.7-5.5).

Conclusions:
An increasing QTc-RS was associated with an increased likelihood of in-hospital mortality
Abstract 12176: Oral Anticoagulant Therapy Following Single-Lead ECG Screening Among Older Patients With Atrial Fibrillation: The VITAL-AF Trial
Authors: Ashburner Jeffrey M , Singer Daniel , Chang Yuchiao , Khurshid Shaan , Lipsanopoulos Ana , Borowsky Leila H , Ellinor Patrick T , McManus David D , Lubitz Steven A , Atlas Steven
Published: April 2022

Introduction:
A substantial proportion of patients with atrial fibrillation do not take oral anticoagulants (OAC). Point of care ECG testing at primary care visits may prompt reassessment of OAC eligibility in patients with AF.

Methods:
VITAL-AF (NCT035115057) was a cluster-randomized trial of AF screening using single-lead handheld electrocardiograms within 16 primary care practices affiliated with Massachusetts General Hospital. The goal of VITAL-AF was to screen for undiagnosed AF. For pragmatic reasons the trial included all individuals aged ≥ 65 years, including those with an established diagnosis of AF. We evaluated screening uptake among prevalent AF patients in the screening arm, OAC initiation among both screening and control patients with prevalent AF, and OAC initiation by screening result (adjusted for stroke/bleed risk factors compared to all patients not screened). OAC use was identified using electronic health record medication lists during the 1-year prior to and following a patient’s study index visit.

Results:
Prevalent AF was present in 2,250 patients (75% on OAC) in the screening arm and 2,343 patients (76% on OAC) in the control arm. 90% of patients in the screening arm were screened at least once during the study period (mean 2.4 times screened). 31.5% had a “Possible AF” and 17.2% had an “Unclassified” automated algorithm screening result during their first screening encounter (40.1% “Possible AF” and 27.4% “Unclassified” during any encounter). Overall, OAC initiation was similar among prevalent AF patients from the screening arm and control arm (
Table
). OAC initiation was higher among screened patients who had a “Possible AF” automated result (Adjusted Odds Ratio 1.14, 95% CI: 1.05-1.24).

Conclusions:
Point of care cardiac rhythm assessment was not associated with significant changes in the use of OAC in patients with a history of AF. However, screened patients not on OAC who had a positive single-lead ECG were more likely to initiate OAC.
Abstract 12177: Analysis of the Primery Factor Which Predicts the Incidence of Esophageal Injury After Catheter Ablation of Atrial Fibrillation
Authors: Ito Miwa , Kanazawa Hisanori , Kawahara Yusei , Hoshiyama Tadashi , Kaneko Syozo , Tsujita Kenichi
Published: April 2022

Background:
Esophageal injury (EI) is a serious complication after radiofrequency catheter ablation (CA) of atrial fibrillation (AF).Although life-threatening complications are rare, CA of posterior wall of left atrium (LA) may result in EI ranging from mild erythema to ulceration. However, predictable factor of EI is unclear. A recent study appreciably suggested that postprocedural upper gastrointestinal tract endoscopy could identify EI, and higher intraesophageal temperature measured by a luminal esophageal temperature monitoring (ETM) was associated with the occurrence of EI. Until now, there is no widely accepted approach to minimize EI caused by CA for AF.

Objective:
We sought to identify risk factors of EI caused by CA for AF, and explore the potential management of EI in this study.

Methods:
Among 568 patients who underwent CA of AF, endoscopy was performed the next day after CA to examine for EI. The incidence of EI was compared between 260 patients who done ETM (ETM group) and 308 patients who didn’t done ETM (Non-ETM group) during CA. The Shortest Distance between esophagus and posterior left atrium measured on contrast Computed Tomography (SD-CT) was also compared between both groups.

Results:
No differences were observed between both groups in total number and amount of applications. However, EI occurred more frequently in Non-ETM group (9/260 patients; 3.4 % vs 27/308 patients; 8.8 %, p=0.042). There was no significant difference in SD-CT between ETM and Non-ETM group. However, SD-CT in patients with EI was significantly shorter than SD-CT in patients without EI, both in ETM (2.3±0.6 vs 4.1±0.8mm, p<0.001) and in Non-ETM group (2.3±0.3 vs 4.1±1.3 mm, p<0.001), respectively. The rising speed of temperature was faster in patients with EI than those without EI (7.6±5.6 vs 10.7±6.2 sec, p=0.025). Maximum arrival temperature of esophagus was higher in patients with EI than those without EI (42.4±5.7 vs 41.2±1.5, p=0.038).Receiver operating characteristic curves were constructed to assess the ability of SD-CT and esophageal temperature to predict EI.

Conclusions:
The use of ETM is safe and necessary in order to prevent the occurrence of EI. The incidence of EI was correlated with SD-CT. ETM reduced EI, especially in patients with short SD-CT.
Abstract 12188: Meta-Analysis Evaluating the Role of Statin in Primary Prevention of Chemotherapy-Induced Cardiotoxicity
Authors: Temtanakitpaisan Yutthapong , Vutthikraivit Wasawat
Published: April 2022

Introduction:
Chemotherapy-induced cardiotoxicity is a well-known consequence after cancer treatment. There were attempts to identify the role of statin for primary prevention of cardiotoxicity. Due to limitations in previous studies (e.g., small sample size and short follow-up period), conclusions cannot be made. We aimed to assess the role of statin in primary prevention of chemotherapy-induced cardiotoxicity by meta-analysis.

Methods:
We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2021. Included studies were published cohort (prospective or retrospective) studies and randomized controlled trials (RCTs) that reported the mean change in left ventricular ejection fraction (LVEF) in breast cancer patients who received anthracycline-based or trastuzumab therapy with or without statin. Patients who received statin were considered as statin group while patients who did not receive statin were considered as control group. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate mean difference (MD) and 95% confidence intervals.

Results:
Three studies from 2011 to 2019 were included in this meta-analysis involving 220 women with breast cancer who undergoing anthracycline-based or trastuzumab therapy (73 in the statin group and 147 in the control group). Mean reduction in LVEF were significantly lower in the statin group as compared with the control group (pooled MD = 6.43%, 95 % confidence interval: 3.61-9.26%, p<0.001, I
2
=88.2%).

Conclusions:
Our study suggested that stain use in breast cancer patients could prevent a decline in LVEF following anthracycline-based or trastuzumab therapy. Further clinical studies are required to ensure our findings.
Abstract 12201: Dissecting the Protective Effect of Phosphodiesterase 3A Hyperactivity on the Heart Using Single Nuclei Sequencing and Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Mücke Michael B , Pallien Tamara , Dierks Philip , Walker-Gray Ryan , Sholokh Anastasiia , Miller Duncan C , Diecke Sebastian , Hubner Norbert , Klussmann Enno
Published: April 2022

Mutations causing hyperactivity of phosphodiesterase 3A (PDE3A) lead to autosomal dominant hypertension with brachydactyly type E. Affected patients suffer from profoundly increased blood pressure and, if untreated, die from stroke at the age of 50 years. Surprisingly, the hearts of affected individuals show little signs of hypertrophic responses to these conditions, indicating a beneficial effect of PDE3A hyperactivity on the damaging mechanisms of the heart. PDE3A inhibition was previously tested as a treatment for heart failure. While
PDE3A
inhibitors lead to short term positive inotropy, treatment with these drugs decreases overall survival of heart failure patients, underlining the importance of PDE3A in the heart. As arterial hypertension is a major risk factor for cardiovascular disease and proves to be a major burden on the healthcare system, dissecting the mechanisms underlying the protective effect of PDE3A can open new paths to preventing and treating heart failure.

We hypothesize that PDE3A activation protects the heart from the detrimental effects of high blood pressure
via
spatially distinct regulation of cAMP levels through its different isoforms, leading to an altered calcium handling of cardiomyocytes.

We are focusing on two mutations causing PDE3A hyperactivity, one in a regulatory hotspot the other in the catalytic domain. Using single nuclei sequencing of left ventricles of rats, genetically engineered to recapitulate the human mutations, we are dissecting the differences in the cell type-specific gene regulatory response to high blood pressure compared to the wildtype. To follow up in a human model system, we used genome editing to introduce the mutations of interest into human induced pluripotent stem cells (hiPSC).

hiPSC lines containing PDE3A mutations as well as isogenic matched control hiPSCs were differentiated to generate hiPSC-derived cardiomyocytes (hiPSC-CMs). Preliminary data from a well-established 2D system show significantly altered calcium handling of PDE3A-mutant hiPSC-CMs. Performing RNA-sequencing, calcium imaging and cAMP measurements in isogenic hiPSC-CMs, we are functionally characterizing the effect of PDE3A activity on cardiomyocyte profile and physiology to a high resolution.
Abstract 12202: Pandemic-Related Diminished Pollution and ST-elevation Myocardial Infarctions
Authors: Aung Sidney , Vittinghoff Eric , Marcus Gregory M
Published: April 2022

Introduction:
The reason for the reduction in ST-elevation myocardial infarctions (STEMI) during the coronavirus disease 2019 (COVID-19) pandemic remains a mystery. Increased particulate matter 2.5 (PM 2.5) is a known risk factor for ST-elevation myocardial infarctions (STEMI), although evidence of the reciprocal relationship (decreased PM 2.5 associated with decreased STEMI incidence) has not been shown. We sought to perform a natural experiment to determine if
decreased
PM 2.5 during the COVID-19 pandemic was associated with a
decrease
in STEMIs.

Methods:
We abstracted daily STEMI events between January 1, 2019 to April 30, 2020 (shelter-in-place [SIP] orders began in March) from the National Emergency Medical Services (EMS) Information System (NEMSIS) database. Incidence rates (events per 10,000 person-years) were calculated using US Census population denominators by US Census Divisions We abstracted average daily PM 2.5 data from across the US from the Environmental Protection Agency (EPA) website. Negative binomial regression models were used to estimate the relationship between levels of PM 2.5 and STEMI rates, adjusting for US Census Division, calendar day of week, calendar month, and calendar year.

Results:
There were 60,722 total STEMI events recorded during the study period. After multivariable adjustment, there were 6% less STEMIs per each 10 μg/m
3
reduction in PM 2.5 (rate ratio 0.94, 95% CI 0.90-0.99, p = 0.016;
Figure
). Using the same multivariate adjustment, there were 373.8 less STEMIs per 10,000 person-years for each 10 μg/m
3
decrease in PM 2.5 (95% CI 69.4-678.1).

Conclusions:
Pandemic-related declines in PM 2.5 levels were associated with significantly less STEMIs across the US. While more pollution is known to increase STEMI risk, this demonstration of the reciprocal relationship provides the most direct evidence that efforts to reduce ambient pollution can prevent the most severe forms of myocardial infarctions.
Abstract 12210: Long-Term Efficacy and Safety of ARRY-371797 (PF-0765803) in an Open-Label Rollover Study in Patients With Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
Authors: Judge Daniel P , Lakdawala Neal K , Taylor Matthew R , Mestroni Luisa , Li Huihua , Oliver Colleen , Angeli Franca S , Lee Patrice A , Macrae Calum
Published: April 2022

Introduction:
Dilated cardiomyopathy due to
LMNA
gene mutations (
LMNA
-DCM) accounts for ~6% of DCM cases and is a life-threatening condition with a high unmet need. No disease-specific treatment targeting the underlying mechanism of disease is currently available. ARRY-371797 (PF-0765803), a potent, selective, oral, small-molecule inhibitor of the p38α MAPK pathway, improved exercise capacity (6MWT) in symptomatic
LMNA
-DCM patients (n=12) in a 48-week, open-label, Phase 2 study.

Methods:
This was an open-label rollover study of the long-term safety and efficacy of ARRY-371797 in symptomatic
LMNA
-DCM patients previously participating in the Phase 2 parent study, with eligible patients continuing on the same dose. Safety and efficacy assessments (6MWT, NT-proBNP, and KCCQ) were performed at Weeks 48, 72, 96, 120, and 144 from treatment initiation in the parent study.

Results:
Eight patients were enrolled (mean [SD] age, 51 [10] years; 4 males). There was a >30 m mean improvement and >10% mean increase in 6MWT distance from parent study baseline up to Week 120 (
Table
), with 3 patients (37.5%) having ≥10% improvement from baseline to Week 144. The decrease in mean NT-proBNP concentration in the parent study was maintained (
Table
). KCCQ Physical Limitation score increased at all visits except Week 48. Changes in KCCQ Clinical Summary and Overall Summary scores were variable. Treatment was generally well tolerated: 3 patients discontinued due to causes not considered treatment-related (UTI and nausea, CRT-D, and LVAD implantation); 2 experienced Grade 1 adverse events considered treatment-related. There were no deaths.

Conclusions:
ARRY-371797 was generally well tolerated, with evidence suggesting preserved exercise capacity over >2 years’ follow-up. Efficacy and safety of ARRY-371797 is being investigated in the REALM-DCM trial, an ongoing, pivotal, Phase 3, randomized, placebo-controlled study in
LMNA
-DCM.