bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10485: Case Fatality and Prior Anticoagulation in Patients with Atrial Fibrillation and First-Ever Ischemic Stroke
Authors: Tiili Paula , Putaala Jukka , Halminen Olli , Kinnunen Janne , Haukka Jari , Linna Miika , Mustonen Pirjo , Airaksinen Juhani , Lehto Mika
Published: March 2022

Introduction:
Thromboprophylaxis of patients with atrial fibrillation (AF) has changed in the past decade. How the changes manifest in real life is yet less studied. This study describes 30-day case fatality and prior anticoagulation in a nationwide cohort of patients with AF and first-ever ischemic stroke during the past decade.

Methods:
FinACAF (Finnish Anticoagulation in Atrial Fibrillation) is a registry-linkage study. Data were collected from several nationwide registries. We followed patients with incident AF between 2009 and 2017 with first-ever ischemic stroke between January 2009 and November 2018. Cox regression model was used to estimate the associations between 30-day case fatality and oral anticoagulation (OAC) if purchased 90 days preceding the stroke, adjusting for age, sex, time of AF diagnosis relative to stroke (new-onset AF vs. prior diagnosis), and stroke year.

Results:
Altogether, 17,924 patients (55% female, median age 79 years with interquartile range 71-86) suffered from first-ever ischemic stroke. Crude 30-day case fatality was 15.4% (95% confidence interval 14.9-15.9, p=0.037). Prior NOAC (hazard ratio 0.69, 0.57-0.84, p<0.001) and prior warfarin (0.78, 0.71-0.86, p<0.001) usage were both associated with lower case fatality compared to those without any OAC in use. There was no significant difference between previous warfarin and NOAC usage. Older age and AF diagnosis registered before the stroke, as opposed to AF diagnosis first recognized together with stroke, were associated with higher case fatality. There was no significant difference between 30-day case fatality when comparing cases by the event year (1.00, 0.98-1.01, p=0.739).

Conclusion:
Previously recorded AF diagnosis was associated with higher 30-day case fatality, although prior use of warfarin and NOAC were associated with decreased mortality compared to no prior OAC use.
Abstract 10496: Cardiac Function in Postmenopausal Women Are Unaltered by Two Decades of Different Physical Activity Levels
Authors: Fischer Mads , Tamariz-Ellemann Andrea S , Hellsten Ylva , Gliemann Lasse
Published: March 2022

Rationale:
In women, the risk of coronary heart disease increases significantly after the onsetof menopause. Exercise and active lifestyle have known benefits such as a significantly reducedrisk of heart failure. To date, most of the knowledge on physical activity induced changes incardiac function in older individuals are based on males and with a sparsity of data from healthypostmenopausal women with differing physical activity and fitness.

Aim:
The aim was to determine the impact of more than twenty years of differing physicalactivity levels and maximal oxygen consumption on cardiac morphology and function inpostmenopausal women.

Method:
The study design was cross-sectional with age-matched non-smoking, non-medicatedhealthy women divided in to three groups based on their self-reported physical activity levelwith regard to intensity and volume over the past two decades. Forty-one women was included(age of 61 ± 1 years; 11 ± 2 postmenopausal years; body mass index 23 ± 3 kg • m
2
) and dividedinto groups based on activity level categorized as sedentary (SED; ≤1 h exercise weekly; n=14);Moderate (MOD; ≥2 ≤6h low/moderate intensity exercise weekly; n=12) and high (HIGH; <4h of moderate/high intensity exercise weekly; n=15). Cardiac function and dimensions wereassessed with transthoracic echocardiography and maximal pulmonary oxygen uptake wasdetermined by graded bike ergometer exercise to exhaustion.

Results:
The three groups displayed significantly different levels of maximum oxygen uptake(24.9 ± 5.8; 30.5 ± 5.8; 38.4 ± 4.4 ml/kg, for SED, MOD and HIGH respectively) (p < 0.01).No differences were observed in resting left ventricular (LV) morphology (LVmass, LVmassindex) systolic function (EF%, GLS and mitral valve S′), diastolic function (E/A ratio, IVRT)or right ventricular function (TAPSE and tricuspid annular velocity S’) between the threegroups.

Conclusions:
These data show that the level of lifelong physical activity and correspondingdifferences in maximal oxygen consumption, may have less impact on left ventricularmorphology and systolic/diastolic function in healthy postmenopausal women than previouslyexpected.
Abstract 10505: S100a12 Aggravates Acute Myocardial Infarction Injury Through Excessive Neutrophil Extracellular Trap Formation
Authors: Zhang Xi , Zhang Xiaolin , Zhang Yujie , Cai Yi , Liu Dan , Tian Xiaoxiang , Yan Chenghui , Yaling Han
Published: March 2022

Introduction:
S100A12 represents a novel biomarker and therapeutic target that regulates cardiovascular disease after its release from myeloid cells. However, the role of S100A12 in the etiology of Acute Myocardial Infarction (AMI) is not well understood. Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of AMI and in the externalization of some S100 family members. Here, we investigated the effect of S100A12 on neutrophils’ function and myocardial injury after AMI.

Methods and Results:
Since S100A12 is a human specific molecule and not expressed in mice, we constructed transgenic (TG) mice expressing S100A12 in myeloid cells. By left anterior descending artery ligation and flow cytometry, we found that S100A12 markedly increased neutrophil infiltration and myocardial injury in TG mice compared to WT mice. Within the infarct zone, more neutrophil extracellular traps (NETs) were observed in TG mice, whereas intraperitoneal injection of DNase I decreased the damage effect of NETs. We used the overexpressing plasmid of S100A12 and observed that S100A12 enhanced the level of NETosis. Whereas, siRNA-mediated S100A12 silencing reduced the production of NETs. By ChIP and dual-luciferase reporter assay we found that Hypoxia-inducible factor-1α (HIF1α) directly bound to the promoter of the S100A12 gene and regulated S100A12 expression. We next used tandem mass tag (TMT) labeling quantitative proteomic technology and discovered that annexin a5 (ANXA5) was a receptor with significantly different expression level in TG compared with WT mice. Finally, we demonstrated that S100A12 increased NETs formation via receptor RAGE and ANXA5.

Conclusions:
Our findings reveal a critical role of S100A12 in regulating neutrophil activation and NETs formation, resulting in aggravated myocardial injury after AMI. In such a process, S100A12 regulates NETosis via the Hif1α-S100A12-ANXA5/RAGE pathway. S100A12 is a useful molecular marker and possible target for treatment for AMI.
Abstract 10506: Cardiac Rehabilitation Visits Have Not Recovered to Pre-Pandemic Levels
Authors: Thompson Mike P , Hou Hechuan , Yaser Jessica , KETEYIAN Steven J , Pagani Francis D , Likosky Donald S , Nathan Hari , Sukul Devraj
Published: March 2022

Introduction:
The COVID-19 pandemic led to temporary restrictions on in-person cardiac rehabilitation (CR) services to mitigate high-risk exposure.

Hypothesis:
In order to better understand the impact of COVID-19 restrictions on CR services, we evaluated changes in the frequency and characteristics of CR visits in 2020 compared with 2019 in a commercially-insured population.

Methods:
We queried the Michigan Value Collaborative statewide claims data registry for outpatient CR visits between 01/01/2019 and 12/31/2020 using CPT codes (93797, 93798) among patients with diagnoses of ischemic heart disease, heart failure, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or heart valve procedure. We described monthly trends in CR visits, and used bivariate analyses to compare changes in the demographics and medical diagnoses for CR visits in 2020 compared with 2019.

Results:
We identified a total of 45,553 CR visits in 2019 and 30,236 visits in 2020, representing a 33.6% relative decline. Monthly CR visits reached a nadir of 138 visits in April 2020 (96.5% reduction compared with April 2019), recovered to 3072 visits in September (-17.9%), and fell again to 2434 visits in December (-34.7%) (Figure). Relative changes in CR visits from 2019 to 2020 varied by diagnosis (p<0.001): -50.3% for heart failure (2931 to 1456, -37.5% for CABG (10121 to 6329), -35.3% for PCI (19669 to 12729), -28.9% for valve surgery (5621 to 3994), and -20.6% for ischemic heart disease (7211 to 5728). There were no significant differences in patient mean age (68.0 vs. 68.1 years, p=0.62) or gender (39.8% vs. 39.9% female, p=0.839) in 2019 compared with 2020.

Conclusions:
Total cardiac rehabilitation visits in 2020 were 33.6% lower compared with 2019, with heterogeneity in declines by underlying eligible diagnosis. Continued monitoring is needed to understand the public health impact of reduced CR use due to the COVID-19 pandemic.
Abstract 10507: Pyridoxamine Protects Against Cardiotoxicity After Doxorubicin Chemotherapy
Authors: Haesen Sibren , Brillouet Aline , de Laat Iris , Vastmans Lotte , Evens Lize , D'Haese Sarah , Wolfs Esther , Deluyker Dorien , Bito Virginie
Published: March 2022

Introduction:
Although doxorubicin (DOX) is an efficient anthracycline agent used to treat cancer, it induces cardiotoxicity and mortality in cancer survivors. Cardioprotection is inadequate. The vitamin B
6
-derivative pyridoxamine (PM) has shown to be cardioprotective in diverse cardiac diseases. Whether PM offers cardioprotection after DOX treatment is unknown. We hypothesized that PM limits cardiac impairment after DOX treatment by reducing cardiac fibrosis and inflammation.

Methods:
Female Sprague Dawley rats were weekly treated with 2 mg/kg DOX or saline IV for 8 weeks. At DOX treatment onset, 2 extra groups received PM (1 g/L) via the drinking water. Echocardiographic (4D) and hemodynamic parameters were assessed at week 8, together with plasma BNP. PCR analysis was performed on left ventricular tissue to evaluate fibrosis and inflammation. Data were compared using 1-way ANOVA, Kruskal-Wallis test or 2-way ANOVA with post-hoc tests as appropriate.

Results:
As shown in Table 1, cardiac impairment by DOX was prevented by PM. In addition, DOX significantly increased the expression of fibrosis markers, such as TGFβ (0.29 ± 0.02 vs. 0.69 ± 0.09 a.u., p<0.0001), LOX (0.055 ± 0.002 vs. 0.590 ± 0.174 a.u., p<0.01), collagen type 1 (0.21 ± 0.02 vs. 0.62 ± 0.11 a.u., p<0.001) and interstitial collagen (4.6 ± 0.3 vs. 7.7 ± 0.6%, p<0.001). DOX also increased the inflammation marker IL-6 (0.13 ± 0.03 vs. 0.73 ± 0.13 a.u., p<0.01). PM treatment significantly lowered all these parameters (p<0001, p<0.001, p<0.01, p<0.01 and p<0.01 respectively).

Conclusions:
In conclusion, our data show that DOX causes dilated cardiomyopathy with reduced ejection fraction, accompanied by cardiac fibrosis and myocarditis. As PM limits this adverse phenotype, it could be a novel cardioprotective strategy for DOX-treated cancer patients.
Abstract 10510: Prognostic Value of the Combination of Cardiac MIBG Imaging and Serum Cholinesterase Level in Patients Admitted for Acute Decompensated Heart Failure
Authors: Tamura Yuto , Yamada Takahisa , Watanabe Tetsuya , Seo Masahiro , Morita Takashi , Kawasaki Masato , Kikuchi Atsushi , Kawai Tsutomu , Nakamura Jun , Kayama Kiyomi , Sakamoto Daisuke , UEDA KUMPEI , Kogame Takehiro , Fujita Takeshi , Nishigaki Keisuke , Fukuda Yuto , Kokubu Yuki , Fukunami Masatake
Published: March 2022

Backgrounds:
Cardiac MIBG imaging provides prognostic information in patients with acute decompensated heart failure (ADHF). On the other hand, serum cholinesterase (CHE) level, which reflect various factors such as hepatic function, inflammation and nutritional status, has been reported to be associated with poor outcome in ADHF patients. However, there is no information available on the prognostic value of the combination of cardiac MIBG imaging and CHE level in patients admitted for ADHF.

Methods:
We studied 579 consecutive patients admitted for ADHF. Cardiac MIBG imaging, echocardiography and venous blood sampling were performed just before discharge. The cardiac MIBG heart-to-mediastinum ratio (late HMR) was measured on the chest anterior view images obtained at 200 min after the isotope injection. The primary endpoint was cardiac event (CE) defined as unplanned heart failure hospitalization and cardiac death.

Results:
During a follow up period of 2.8±0.9 years, 196 patients reached the primary endpoint. On multivariate Cox analysis, late-HMR (p<0.0001, HR 1.82 [1.34-2.47) and serum CHE level (p=0.047, HR 1.40 [1.01-1.94]) were significantly associated with CE after adjustment for age, sex, left ventricular ejection fraction, history of hypertension, diabetes mellitus, hemoglobin, blood urea nitrogen and albumin. Kaplan-Meier survival curve analysis demonstrated that patients with both low serum CHE level (<217 U/L=median value) and late-HMR (<1.66=median value) had a significantly increased risk of CE in than those either or none of them.

Conclusion:
The combination of cardiac MIBG imaging and serum CHE level would be useful for stratifying ADHF patients at risk for cardiac events.
Abstract 10513: Early Follow-Up After Heart Failure Hospitalizations Remains Low and Variable Across Hospitals: Insights from the Michigan
Authors: Thompson Mike P , Abshire Chelsea , Cascino Thomas , Syrjamaki John , Nathan Hari
Published: March 2022

Introduction:
Early outpatient follow-up may improve outcomes for hospitalized heart failure patients, and is being considered as an ACC/AHA heart failure performance measure.

Hypothesis:
We evaluated patterns and determinants of early outpatient follow-up after heart failure hospitalization across Michigan hospitals.

Methods:
The sample used in this analysis included all patients hospitalized with a primary diagnosis of heart failure between January 1, 2017 and December 31, 2019 in the Michigan Value Collaborative statewide multipayer claims data registry. Early follow-up was defined as an outpatient evaluation and management visit within 7 days of discharge. Multilevel mixed-effects models were used to evaluate risk-adjusted early follow-up rates after heart failure hospitalization, adjusting for patient and discharging hospital factors.

Results:
A total of 17,203 of 39,505 (43.6%) patients hospitalized for heart failure had an early follow-up visit after discharge, which increased from 41.3% in 2017 to 43.0% in 2018 and 46.1% in 2019 (p<0.001). Predictors of early follow-up include male sex, increasing age, commercial insurance coverage, angina, coagulopathy, lung disease, metabolic disorders, arrhythmia, vascular disease, hospital not-for-profit status, non-teaching hospital, and non-rural location. After adjustment, hospital-level rates of early follow-up ranged from 18.1% to 65.7%, with a median of 42.0% (Figure). Patient and hospital factors account for 1.4% and 36.3% of the variation in hospital-specific rates of early follow-up, with 62.3% of the variation left unexplained.

Conclusions:
Less than half of hospitalized heart failure patients have an early follow-up after discharge, with patient factors accounting 2% of the variation. A more thorough understanding of the determinants of successful early follow-up after heart failure hospitalization and its impact on outcomes will better inform quality improvement efforts.
Abstract 10516: Identification of a PCSK9-LDLR Disruptor Macrocycle with
in vivo
Function
Authors: Brousseau Margaret E , Clairmont Kevin B , Spraggon Glen , Flyer Alec N , Golosov Andrei A , Grosche Philipp , AndrÃ© JÃ©rÃ´me , Caplan Shari , Chen Guanjing , Fan Li , Gattlen Raphael , Koch Alexander , Lewis Ian , Li Jingzhou , Liu Eugene , Lubicka Danuta , Marzinzik Andreas , Nakajima Katsumasa , Nettleton David , Ottl Johannes , Pan Meihui , Patel Tajesh , Pickett Stephanie , Poirier Jennifer , Reid Patrick C , Pelle Xavier , Subramanian Vanitha , Vera Victoria , Xu Mei , Yang Lihua , Yang Qing , yu jinghua , Zhu Guoming , Monovich Lauren G
Published: March 2022

Elevated LDL-C is a major risk factor for atherosclerotic cardiovascular disease, the leading cause of death worldwide. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has pronounced effects on LDL-C levels via its modulation of hepatic LDL receptors (LDLR), the main pathway for cholesterol removal from the circulation. The epidermal growth factor precursor homology domain A (EGF-A) of the LDLR serves as a primary contact with PCSK9 via a flat interface, presenting a challenge for identifying small molecule PCSK9-LDLR disruptors. We employed an affinity-based screen of 10
13
in vitro
-translated macrocyclic peptides to identify high affinity PCSK9 ligands that utilize a novel, induced-fit pocket and partially disrupt the PCSK9-LDLR interaction (Hit 1 - PCSK9-LDLR FRET, IC
50
2 nM, A
max
41%). Structure-based design led to

13
PCSK9i

, a molecule with enhanced
in vitro
function (PCSK9-LDLR FRET, IC
50
2 nM, A
max
78%) and pharmacokinetic properties suitable for
in vivo
evaluation. To determine if

13
PCSK9i

’s functional activity
in vitro
would translate
in vivo
, C57BL/6 mice were dosed with vehicle or

13
PCSK9i

via
subcutaneous injection twice-daily for 3 days, and blood and liver were collected for the measurement of plasma total cholesterol (TC) and hepatic LDLR density. A PCSK9 antibody was included as a positive control. As illustrated in the figure,

13
PCSK9i

increased hepatic LDLR density in a dose-dependent manner. Despite being 1/100
th
its size,

13
PCSK9i

(MW = 1.65 kDa) increased hepatic LDLR density on par with a PCSK9 antibody (MW = 144 kDa). Plasma TC levels were significantly reduced versus vehicle in all

13
PCSK9i

dose groups, with similar reductions noted in the

13
PCSK9i

30 mg/kg and PCSK9 antibody groups (44% and 48%, respectively). In summary,

13
PCSK9i

breaks new ground with its previously undescribed allosteric mechanism and, in turn, as the smallest molecule identified to date with
in vivo
PCSK9-LDLR disruptor function.
Abstract 10519: The Epidemiology of Race- and Sex-Specific Hospitalizations for Abdominal Aortic Aneurysms
Authors: Li Shimena R , Reitz Katherine M , Gabriel Lucine , Phillips Amanda R , Shireman Paula K , Eslami Mohammad , Edith Tzeng
Published: March 2022

Introduction:
Established predominantly among White males, early detection of abdominal aortic aneurysms (AAA) with risk-factor guided screening decreases AAA-related mortality. Minimal epidemiologic data exists for AAA in racial and sex minority groups despite having increased morbidity and mortality following repair.

Methods:
Using data from the National Inpatient Sample and US Census (2012-18), we quantified age, race, and sex-specific incidences of intact and ruptured AAA (iAAA, rAAA) hospitalizations, associated risk factors, and in-hospital mortality. Adjusted odds ratios (OR) quantified AAA hospitalization and mortality risks. Interaction terms evaluated subgroups.

Results:
Of 1,728,374,183 US residents (78% White, 13% Black, 6% Asian; 51% female), 211,501,703 were hospitalized (65% White, 14% Black, 3% Asian; 58% female) with 291,850 for AAA (82% White, 6% Black, 2% Asian; 23% female). AAA hospitalizations were highest for Whites and males (
Fig
). For iAAA, compared to Whites, Blacks (OR 0.5 [95%CI 0.4-0.5]) and Asians (OR 0.9 [95%CI 0.8-0.9]) and compared to males, females (OR 0.3 [95%CI 0.3-0.3]) had reduced odds of hospitalization. For rAAA, reduced odds of hospitalization for Blacks (OR 0.5 [95%CI 0.5-0.6]) and females (OR 0.3 [95%CI 0.3-0.3]) persisted, but not for Asians (OR 1.0 [95%CI 0.8-1.2]). In subgroup analysis, associations between AAA hospitalizations, race and sex were smaller and closer to Whites and males for Black females and Blacks and females who were older or had peripheral vascular disease (PVD; P-interactions <0.001). Female sex (OR 1.5 [95%CI 1.4-1.7]) but not Black and Asian races, was associated with increased mortality.

Conclusions:
Black and Asian races and female sex were associated with substantial decrease while older age and PVD conferred increase in the contemporary incidence and odds of AAA hospitalizations. However, AAA screening guidelines do not include PVD or race-specific differences. Changes may be warranted.
Abstract 10520: Emerging Cardiovascular Side Effects of Selective and Non-Selective Immunotherapies in Cancer Patients: 2021 Results from the Global WHO Database
Authors: Prasai Astha , Pokharel Saraswati , Sharma Umesh
Published: March 2022

Introduction:
Immune checkpoint inhibitors (ICIs), and adoptive cell transfer (ACT) - which involves collecting and using patient’s own immune cells to treat their cancer, are two rapidly emerging therapeutic modalities for various advanced stage cancers. Emerging cardiovascular side effects of ICIs and ACTs are currently being recognized.

Objective:
We analyzed the newly reported side-effect profiles of FDA-approved ICIs (anti-CTLA-4, anti-PD-1 and anti-PD-L1) and ACTs (also known as CAR-T therapy).

Methods:
We utilized the global data available in VigiBase®, World Health Organization’s global database for adverse drug reactions (ADRs), maintained by the Uppsala Monitoring Centre. We extracted information on reports of suspected ADRs, also called Individual Case Safety Reports (ICSRs). ICSRs of ICI and ACT therapy on cardiovascular system were extracted, and the side effect profile of the two groups of immunotherapies were systematically analyzed.

Results:
Based on the records obtained to-date, a total of 6,000 cardiovascular ADRs caused by ICIs (Ipilimumab, Nivolumab, Pembrolizumab, Cemiplimab, Atezolizumab, Avelumab and Durvalumab), and 500 ADRs by ACTs (Kymriah, Yescarta, Tecartus, Brevanzi and Abecma) have been reported. ICI therapies were predominantly associated with myocarditis (1098), cardiac failure (614), acute coronary syndrome (548) and pericarditis/pericardial effusion (516). ACT therapies were associated with tachyarrhythmia (263), cardiac arrest (44) and cardiorenal events (25). A propensity analysis demonstrated ICIs to be associated with autoimmunity-related ADRs, whereas ACTs were associated with acute cytokine release-related ADRs.

Conclusions:
Using a large-scale global WHO data platform, we have identified unique tendencies for cardiovascular ADRs resulting from non-selective (ICIs) and highly-selective (ACTs) immunotherapies for cancer: the former is associated with serious autoimmune effects, and the latter is associated with acute cytokine-release-related ADRs.
Abstract 10521: Frequency and Impact of Virtual Follow-Up Visits After Heart Failure Hospitalizations: Insights from Michigan
Authors: Thompson Mike P , Yaser Jessica , Cascino Thomas , Nathan Hari , Ellimoottil Chad S
Published: March 2022

Introduction:
Outpatient follow-up after heart failure hospitalization has been shown to reduce readmission and emergency department (ED) visits.

Hypothesis:
We sought to evaluate the use of virtual follow up-care heart failure hospitalizations in a commercially insured population.

Methods:
We queried the Michigan Value Collaborative multipayer claims database for heart failure hospitalizations in patients discharged to home or home health between 7/20-11/20. We identified follow-up visits as outpatient office visits within 30 days of discharge, and categorized each patient as having an in-person only, virtual-only (GT or 95 modifier code), both virtual and in-person, and no follow-up visit. Multivariable logistic and linear regression was used to evaluate the association between follow-up visit type and 30-day readmissions, ED visits, and price-standardized episode spending.

Results:
A total of 2415 patients were discharged alive after a heart failure hospitalization: 94 (3.9%) patients had a virtual-only follow-up visit, 258 (10.7%) had both in-person and virtual visits, 1551 (64.2%) had in-person only follow-up visits, and 512 (21.2%) had no follow-up within 30 days of discharge. Adjusted analyses revealed that patients receiving both virtual and in-person visits had similar rates of 30-day readmissions (aOR=0.73, 95% CI: 0.42, 1.27), ED visits (aOR=0.52, 0.26, 1.07), and episode spending (adjusted difference= -$1508, 95% CI: -$3835, $821;
Table
). However, patients receiving only virtual visits or no follow-up had significantly higher 30-day readmissions (aOR=2.31, 95% CI: 1.21, 4.42) and episode spending (adjusted difference= $1974, 95% CI: $206, $3742) compared to in-person visits.

Conclusions:
Virtual follow-up visits occurred in nearly 15% of heart failure patients, but had mixed results on patient outcomes. More evidence is needed to support the role of virtual-only follow-up visits after heart failure hospitalizations.
Abstract 10527: Clinical Characteristics and Cardiovascular Outcomes of Atrial Fibrillation (af) with Coexisting Left Bundle Branch Block (lbbb)-Analyses from National Inpatient Sample (2013-2014)
Authors: Ijaz Sardar H , Jamal Shakeel , Bailey Beth , Minhas Abdul , Kichloo Asim , Hassan Jawad , Kanjwal Khalil
Published: March 2022

Introduction:
Left bundle branch block (LBBB) because of dyssynchrony is a risk factor for heart failure (HF). We evaluated the baseline characteristics and comparative outcomes of atrial fibrillation (AF) patients with co-existing LBBB.

Hypothesis:
AF with concomitant LBBB is associated with poor cardiovascular outcomes.

Methods:
We conducted a retrospective analysis of hospitalizations for AF with and without LBBB from the National Inpatient Sample (NIS) between 2013 and 2014. Billing codes (International classification of diseases, 9th revision) were used to identify the target population.

Results:
A total of 1,531,704 hospitalizations for AF were identified, out of these, 1,496,742 hospitalizations had no LBBB and 34,952 hospitalizations had LBBB. AF with LBBB cohort was older with mean age (77.8 vs 75.3, p <0.001), had slightly lower proportion of females (48.4% vs 48.9%, p <0.04), higher proportion of white race (85.2% vs 82.3%, p <0.001) and had a statistically significant higher disease burden including hypertension (73.3% vs 70.2%, p <0.001), diabetes mellitus (27% vs 26.3%, p <0.001), ischemic heart disease (58% vs 43.3%, p <0.001), peripheral arterial disease (8% vs 6.9%, p <0.001), congestive HF (59% vs 40.7%, p <0.001) and tobacco use (27.8% vs 27%, p 0.001) when compared to AF without LBBB cohort. AF with LBBB had worse inpatient cardiovascular outcomes including cardiogenic shock (adj OR 1.81, CI 1.68-1.96), cardiac arrest (adj OR 1.71, CI 1.58-1.84), ventricular arrhythmias (adj OR 2.05, CI 21.97-2.12) and complete AV block (adj OR 3.36, CI 3.11-3.65).

Conclusions:
LBBB is a poor prognostic indicator in patients admitted for AF and is associated with worse cardiovascular outcomes. Aggressive management of AF in patients with LBBB may improve the clinical outcomes. Further clinical studies are required to study this relationship.
Abstract 10528: Exaggerated Inspiratory Muscle Metaboreflex in Heart Failure with Preserved Ejection Fraction
Authors: Smith Joshua R , Hammer Shane M , Bruhn Eric J , Borlaug Barry A , Olson Thomas P
Published: March 2022

Introduction:
Heart failure patients with preserved ejection fraction (HFpEF) may exhibit inspiratory muscle dysfunction potentially contributing to exercise intolerance. Activation of neural afferents in response to inspiratory muscle contraction (metaboreflex) elicits increases in mean arterial pressure (MAP) and leg vascular resistance (LVR) through enhanced sympathetic outflow leading to decreases in leg blood flow (LBF) in healthy humans. It is unknown if HFpEF patients exhibit exaggerated cardiovascular responses to inspiratory muscle metaboreflex activation.

Hypothesis:
We hypothesize that patients with HFpEF will exhibit a greater increase in MAP and LVR with a decrease in LBF during inspiratory muscle metaboreflex activation than controls.

Methods:
HFpEF patients (n=15, 10M/5W, 69±10 yrs; 33±4 kg/m2) and controls (n=14; 10M/4W; 70±8 yrs; 28±4 kg/m2) performed inspiratory resistive breathing tasks (IRBT) at 2% and 60% of their maximal inspiratory pressure. During the IRBTs, the breathing frequency was 20 breaths/min with a 50% duty cycle. At rest and during the IRBTs, MAP was measured by photoplethysmography, venous norepinephrine was measured, LBF was measured by near-infrared spectroscopy and indocyanine green dye injections, and LVR was calculated.

Results:
During the 2% IRBT, there were no differences between groups in the changes from rest in MAP (HFpEF: 2±4 vs. CTL: 3±4 mmHg) or LBF (HFpEF: 1±14 vs. CTL: 1±12%) (both, p>0.05). During the 60% IRBT, venous norepinephrine increased from rest in HFpEF and controls (p<0.05), while no differences existed between groups (p>0.05). During the 60% IRBT, HFpEF patients, compared to controls, exhibited a greater increase from rest in MAP (HFpEF: 16±7 vs. CTL: 10±6 mmHg) and LVR (HFpEF: 76±45 vs. CTL: 32±19%) coupled with a greater decrease in LBF (HFpEF: -32±14 vs. CTL: -17±9%) (all, p<0.05).

Conclusions:
These data indicate that patients with HFpEF exhibit exaggerated cardiovascular responses with inspiratory muscle metaboreflex activation compared to healthy individuals. These findings have important implications for the integrative physiology of exercise in HFpEF patients.
Abstract 10530: Stretch-Induced Arrhythmias Are Increased by Microtubule Detyrosination in a TRPA1 Dependent Manner in the Rabbit Heart
Authors: Bak Jessi J , Quinn T Alexander
Published: March 2022

Introduction:
Clinical evidence indicates that in hypertension, acute fluctuations in blood pressure can trigger ventricular arrhythmias. Single cell rabbit studies suggest that these stretch-induced arrhythmias (SIA) are related to increased microtubule (MT) density or detyrosination and depend on transient receptor potential ankyrin 1 channels (TRPA1). However, whether these mechanisms of SIA apply to the whole heart is unknown.

Hypothesis:
An increase in MT density or detyrosination will reduce the threshold for SIA in the whole heart and be dependent on TRPA1.

Methods:
Isolated rabbit hearts were instrumented with surface electrodes to monitor electrical activity and an intraventricular balloon to alter LV load. Transient changes in LV volume were applied to induce SIA (50-500μL, 10mL/s, 20 repetitions of each volume separated by 30s). SIA incidence
vs
volume was used to calculate the volume that resulted in a 50% SIA incidence (V
50
). Paclitaxel (5μM) was applied alone to increase MT density and detyrosination or in combination with parthenolide (10μM) to prevent the increase in detyrosination or HC-030031 (10μM) to block TRPA1. Voltage optical mapping was used to determine the nature of SIA. MT density was assessed by immunofluorescence in isolated LV myocytes.

Results:
Paclitaxel reduced the threshold for SIA (decreased V
50
versus
control: 133±16
vs
173±11μL;
n
=8
, p
=0.02 by paired t-test) and resulted in the conversion of some stretch-induced ectopy to sustained activity. These effects were prevented by reduced detyrosination with parthenolide (262±27
vs
256±26μL;
n
=8
, p
=0.75). Paclitaxel also increased MT density
versus
control, however this was not prevented by parthenolide (63±3 and 60±3 vs 50±4%;
n
=15,
p
=0.04 by one-way ANOVA). The decreased V
50
and occurrence of sustained arrhythmias with paclitaxel was also prevented by TRPA1 block with HC-030031 (249±26
vs
237±27μL;
n
=8,
p
=0.60). Optical mapping revealed stretch-induced ectopic excitation originating from the LV freewall, which resulted in re-entrant activity with paclitaxel.

Conclusions:
An increase in MT detyrosination leads to a reduced threshold for SIA and the triggering of sustained arrhythmias in the whole heart in a TRPA1 dependent manner.
Abstract 10535: Tissue-Incubation-Chamber Provides Enhanced Viability of Porcine Aortic Valve Tissue in Dynamic Long-Term Culture
Authors: Dittfeld Claudia , Winkelkotte Maximilian , Schmieder Florian , Behrens Stephan , Jannasch Anett , Matschke Klaus , Sonntag Frank , Tugtekin Sems-Malte
Published: March 2022

Introduction:
Aortic valve (AV) stenosis is caused by fibrosis and calcification of the three-layered valve tissue. Current
in vitro
and
in vivo
models are insufficient to reflect cell-cell or cell-matrix interaction and pathophysiological processes. Therefore a novel tissue incubation chamber (TIC) enabling dynamic AV-tissue culture in micro-physiological systems (MPS) was designed to improve emulation of the extreme
in vivo
conditions of the cardiac cycle. This pilot study aims to verify tissue viability to ensure applicability of the TIC in conjunction with a MPS in AV research.

Methods:
Porcine AV tissue of 3x5 mm is maintained in the TIC for 14 days within a conventional cell incubator under sterile conditions. A pump-chip able to generate a pulsatile flow rate of 13.4 μl/s (150 bpm) accomplishes average shear forces of 0.017 dyn/cm
2
. Two viability assays were performed to compare dynamic and static setups. AV samples were snap frozen, cryo sectioned and intracellular LDH activity in central tissue regions was visualized using a Tetrazolium-based dye. In addition, a Resazurin reduction assay (50-300 μM) was applied.

Results:
The LDH-viability stain reveals no significant reduction of viable tissue sections in dynamically incubated AV tissues (96.4 ± 1.3 %) but a significant decrease in the static counterparts (67.8 ± 4.7 %, n=3). The Resazurin assay on the other hand showed significant viability reduction in dynamic setup after 12 days (57 ± 5.4 %), whereas significant reduction was already detected in static culture after 8 days (57.5 ± 15.1 %, n=4). Due to the discrepancy of both viability assays, an inadequate diffusion rate based on structural AV tissue integrity was hypothesized with the need to adapt Resazurin assay concentration. A saturation curve conducted consecutively determined an optimal Resazurin concentration of 300μM to be used in upcoming AV tissue culture (n=4).

Conclusion:
Enhanced viability of porcine AV tissue following dynamic incubation in the TIC was achieved but further adaptation in terms of higher shear forces and a more physiological sample fixation is envisioned. Dynamically cultured AV tissue cultures in the novel TICs offer a relevant improvement for investigation of AV pathophysiology.
Abstract 10538: Differences in Oxygen Uptake Kinetics Across Ejection Fraction Phenotypes in Heart Failure
Authors: Hammer Shane M , Koepp Katlyn E , Smith Joshua R , Bruhn Eric J , Borlaug Barry A , Olson Thomas P
Published: March 2022

Introduction:
Peripheral factors contribute to exercise limitations in heart failure (HF) with preserved ejection fraction (HFpEF) and may be related to excess regional adiposity. Slowed oxygen uptake (VO
2
) kinetics are common in HF with reduced ejection fraction (HFrEF) and reflect peripheral O
2
transport impairments and abnormal muscle metabolic control. Differences in VO
2
kinetics between HFpEF and HFrEF may reveal phenotype-specific impairments in peripheral O
2
transport but remain unknown.

Hypothesis:
We hypothesized that VO
2
kinetics are slower in HFpEF (compared to HFrEF) and associated with greater leg adiposity.

Methods:
Patients with HFpEF (n=12; 3 women; 66±6 yrs; 29±3 kg/m
2
; ejection fraction: 59±5%), HFrEF (n=12; 3 women; 62±9 yrs; 28±4 kg/m
2
; ejection fraction: 37±8%), and controls (n=12; 3 women; 65±5 yrs; 28±3 kg/m
2
) cycled at 20 W for 5 minutes prior to a maximal exercise test to determine VO
2peak
. Age, sex, and BMI were matched by design and were not different among groups (p>0.05). A monoexponential function with a time delay was used to describe the VO
2
transition from rest to 20 W and calculate the O
2
deficit. Leg fat mass was measured via dual energy X-ray absorptiometry.

Results:
VO
2peak
was lower in HFpEF (18.6±6.2 mL/kg/min) and HFrEF (19.0±3.7 mL/kg/min) compared to controls (26.0±3.1; both p<0.05). Amplitude (HFpEF: 507±97 mL/min; HFrEF: 443±91 mL/min; controls: 477±117 mL/min) and time delay (HFpEF: 16±9 s; HFrEF: 11±7 s; controls: 11±6 s) were not different among groups (p>0.05). The time constant was slower in HFrEF compared to controls (45±9 s vs. 32±6 s; p=0.03) and further slowed in HFpEF (66±18 s; p<0.001). The O
2
deficit was significantly greater in HFpEF (895±201 mL) and HFrEF (649±131 mL) compared to controls (590±125 mL; both p<0.05). There were no differences in percent leg fat mass among groups (HFpEF: 33±8%; HFrEF: 31±6%; controls: 34±9%) and no associations were detected between percent leg fat mass and any VO
2
parameters (all p>0.05).

Conclusions:
Patients with HFpEF exhibited slower VO
2
kinetics compared to HFrEF with no association to leg adiposity. These data suggest differences in peripheral O
2
transport and intramuscular metabolic control abnormalities between HF phenotypes.
Abstract 10540: Worsening Racial Disparity in Waitlist Mortality for Pediatric Heart Transplant Candidates Since the 2016 Pediatric Heart Allocation Policy Revision
Authors: Wright Lydia K , Gajarski Robert J , Phelps Christina , Hoffman Timothy M , Lytrivi Irene , Magnetta Defne , Shaw Fawwaz R , Thompson Consuela , Weisert Molly , Nandi Deipanjan
Published: March 2022

Introduction:
The US Pediatric Heart Allocation Policy was recently revised with the goal of lowering waitlist mortality. Effective March 2016, these rules significantly changed the requirements for priority status. We evaluated the hypothesis that this change, which has led to an increase in status exceptions, has worsened known racial disparities in waitlist outcomes.

Methods:
Children in the Pediatric Heart Transplant Study database listed at a US center from January 2012 - June 2020 were included and stratified by listing before (Era 1) or after (Era 2) allocation policy change on March 22, 2016. Competing risk survival analysis was performed to evaluate endpoint of death or deterioration on the waitlist with transplant treated as a competing risk.

Results:
Compared with white children (n=2,648), non-white children (n=1,441) were more likely to have an underlying diagnosis of cardiomyopathy (49% vs. 39%, p<0.001), be currently hospitalized (81% vs. 71%, p=0.007) and supported with a ventricular assist device (VAD) (12% vs 9%, p=0.005) at the time of listing. Waitlist mortality was similar in white and non-white children in Era 1, but worse for non-white children compared to white children in Era 2 (Figure). In multivariable analysis controlling for diagnosis, age and severity markers, non-white children had a significantly higher waitlist mortality only if listed after the policy change (Era 1: sHR 1.18 [95%CI 0.88 - 1.59] vs. Era 2: sHR 1.52 [95%CI 1.14 - 2.02]). Hispanic ethnicity was not associated with waitlist mortality in either period when controlling for other risk factors.

Conclusions:
Widening racial disparities in waitlist mortality may be an unintended consequence of the 2016 Pediatric Heart Allocation Policy revision. Additional analyses may help the transplant community understand the degree to which this policy (i.e. prioritized listing status and exceptions) vs. unrelated changes in care differentially contribute to these disparities.
Abstract 10545: Hospital Teaching Status Increases the Frequency of Measurement of Right Heart Pressures in Patients Hospitalized for Heart Failure: A Nationwide Analysis
Authors: Aguilar-gallardo Jose S , ROMEO Francisco , Correa Ashish A , Contreras Johanna P
Published: March 2022

Introduction:
Measurement of right heart pressures is a useful, yet non-routine diagnostic tool whose indications in heart failure are not standardized. In this study, we investigated teaching status as an independent predictor of measurement of right heart pressures.

Methods:
This was a retrospective cohort study using the 2018 Nationwide Inpatient Sample that included adult patients with a primary diagnosis of heart failure that were admitted to urban hospitals. Rural hospitals were excluded. The primary outcome was measurement of right heart pressures. Secondary outcomes included performance of coronary angiogram, length of stay, total hospitalization charges. Multiple regression analysis was used to adjust for hospital bed size, region, and type of ownership, as well as the patient’s age, type of insurance, income quartile, Charlson Comorbidity Index, chronic obstructive pulmonary disease, pulmonary hypertension, and other relevant comorbidities with a p-value <0.2 in univariate screen. Statistical analysis was performed using Stata 17.0.

Results:
A total of 1,117,134 (weighted) heart failure hospitalizations were studied, of which a total of 31,085 underwent measurement of right heart pressures. Multivariate regression analysis revealed that hospital teaching status was associated with a greater frequency of measurement of right heart pressures with an odd ratio (OR) 3.03 (95% CI, 2.38 to 3.89, p=0.000). The secondary outcomes of coronary angiogram, length of stay, and total hospitalization charges were also increased.

Conclusions:
Teaching status increases the frequency of measurement of right heart pressures in heart failure hospitalizations. This might highlight the need to standardize indications applicable across the spectrum of hospital settings.
Abstract 10547: Communication of Potential Adverse Drug Reactions in Patients Undergoing Percutaneous Coronary Intervention
Authors: Pettersen Trond , Allore Heather , Bendz Bjorn , Borregaard Britt , Fridlund Bengt , Ghaderi Sara , Larsen Alf Inge , Nordrehaug Jan Erik , Rasmussen Trine B , Rotevatn Svein , Schjøtt Jan , Valaker Irene , Norekvål Tone Merete ,   CONCARD Investigators
Published: March 2022

Background:
Patients need information on all aspects of prescribed drug therapy to make informed decisions about their treatment for autonomy.

Purpose:
This study assessed whether patients received information about potential adverse drug reactions (ADRs) from prescribed drug therapy before or after discharge following percutaneous coronary intervention (PCI). Furthermore, we sought to estimate associations with socio-demographics and concerns related to prescribed drug therapy.

Methods:
CONCARD
PCI
is a prospective multicentre cohort study including 3424 patients undergoing PCI. The study was conducted between June 2017 and May 2020 at seven large referral PCI centres in two Scandinavian countries. Clinical data were collected from patients’ medical records. Socio-demographic characteristics were obtained by self-report during index hospitalization. Four questions from the Heart Continuity of Care Questionnaire were used to determine if information about potential ADRs was provided before or after discharge. The Specific-Concerns Scale of the Beliefs about Medicines Questionnaire was used to assess concerns related to prescribed drug therapy. Logistic regression estimated whether lack of information was associated with sociodemographic characteristics.

Results:
Most patients were men (78%), with a mean age of 66 years (SD11, range 20-96 years) and married or living with a partner (75%). Before discharge from hospital, 59% reported being informed of potential ADRs and 50% were informed what to do if ADRs occurred. After hospital discharge, 26% reported having reviewed potential ADRs with healthcare providers, and 24% had reviewed what to do if ADRs occurred. Those who were not informed had increased concerns about their prescribed drug therapy compared to those who were informed at both time points (p<0.001). Women (51%) were less likely to receive information about potential ADRs than men (63%) (p<0.001). However, there were no substantial associations with age, education, income, or marital status.

Conclusion:
Four in ten patients reported not receiving information on potential ADRs from prescribed drug therapy, and this applied especially for women. Efforts to improve communication on ADRs and gender equity should be a priority.
Abstract 10549: Clinical Significances of Left Atrial Volume vs Function in Nonischemic Cardiomyopathy
Authors: Okune Mana , Yasuda Masakazu , Soejima Naoko , Kazuyoshi Kakehi , Kawamura Takayuki , Kurita Takashi , Nakazawa Gaku , Iwanaga Yoshitaka
Published: March 2022

Introduction:
Left atrium (LA) structure/function is reported to provide incremental prognostic information in patients with heart failure. However, its clinical impact is not fully elucidated in nonischemic cardiomyopathy (NICM). Therefore, we explored the clinical significance in patients with NICM, especially by clarifying the different roles between LA volume and emptying fraction.

Methods:
Consecutive patients with NICM who underwent cardiac magnetic resonance were analyzed and followed. Cox regression models were used to estimate hazard ratios (HRs) for major cardiovascular events (MACE) related to LA volume and emptying fraction.

Results:
Among the 625 patients with NICM including left ventricle non-compaction, dilated cardiomyopathy, hypertrophic cardiomyopathy, cardiac sarcoidosis, and cardiac amyloidosis (mean age; 64.4 ± 14.2 years, and female; 39.7%), 133 had a history of AF at baseline. Baseline AF was associated with both higher LA volume and lower emptying fraction independently; however, it was not associated with increased MACE (P = 0.245). New-onset AF developed in 5.9% of the patients during a median follow-up of 20.3 months, with maximum LA volume as its strong and independent predictor (P < 0.001, the area under the ROC curve AUC of 0.795). It was superior to LA emptying fraction (Figure A). In Kaplan-Meier analysis, patients with new-onset AF showed increased MACE compared with those of sinus rhythm or baseline AF (P = 0.002). New-onset AF and LA emptying fraction were independent predictors of MACE (HR: 2.28, 95% CI: 1.20-3.97, and HR: 0.98, 95% CI: 0.96-0.99, respectively) after adjusting for age, gender, body mass index, and diagnosis. Maximum LA volume alone was not associated with MACE (Figure B).

Conclusions:
Both LA volume and function were independently associated with baseline AF in patients with NICM. Maximum LA volume predicted the incidence of new-onset AF best, and only LA emptying fraction was associated with a worse prognosis.
Abstract 10550: Mental Health Disorders and Readmissions Following Acute Myocardial Infarction
Authors: Sreenivasan Jayakumar , Kaul Risheek , Khan Mohammad S , Malik Aaqib H , Usman Muhammad , Michos Erin
Published: March 2022

Introduction:
Hospital readmissions following an acute myocardial infarction (AMI) are associated with increased mortality and morbidity. The association of mental health disorders (MHD) and risk of readmission following AMI is not well studied.

Hypothesis:
We hypothesized that among patients with AMI, a co-morbid diagnosis of MHD is associated with increased risk of readmission.

Methods:
We analyzed the National Readmission Database for all adult AMI hospitalizations from 2016 to 2017. Co-morbid diagnoses of major depression, bipolar disorders, anxiety disorder and schizophrenia/other psychotic disorders were obtained using appropriate ICD-10 CM diagnostic codes. The primary outcome was 30-day all-cause unplanned readmission. A Cox-regression analysis was used to identify the association of MHD and risk of 30-day readmission adjusted for demographics, medical and cardiac comorbidities, and coronary revascularization.

Results:
We identified a total of 10,45,752 hospitalizations for AMI with a mean age of 66.6±12.9 years with 37.6% being females. The prevalence of any MHD was 15.0±0.9%. Readmission rates after AMI were higher for those with MHD compared to those without (
Figure
). After adjusting for potential confounders, comorbid diagnosis of major depression [rate 12.2%±0.5%, hazard ratio (HR) 1.11 (95% CI 1.07-1.15), p<0.001], bipolar disorders (rate 13.6±0.5%, HR 1.32 (1.19-1.45), p<0.001), anxiety disorders (rate 10.9±0.4%, HR 1.09 (1.05-1.13), p<0.001) and schizophrenia/other psychotic disorders (rate 17.5±0.6%, HR 1.56 (1.43-1.69), p<0.001) were independently associated with a higher risk of 30-day readmission compared to those with no comorbid MHD.

Conclusions:
Major depression, bipolar disorders, anxiety disorders and schizophrenia/other psychotic disorders are significantly associated with a higher independent risk of 30-day all-cause hospital readmissions among AMI hospitalizations in the United States.