bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16430: Early Urine Sodium Response After Ambulatory Diuretic Bolus to Avoid Heart Failure Hospitalization
Authors: Burpee Laura , Desai Akshay , Smallwood Jennifer , Young Michelle , Stevenson Lynne , Cooper Irene , Navarro-Velez Kristina , Shea Elaine , Stevens Craig , Weiffenbach Cindy , Weintraub Joanne , Mehra Mandeep
Published: July 2021

Introduction:
Ambulatory heart failure management may increasingly include administration of intravenous diuretics in an outpatient setting, but it is difficult to know when response will be adequate to avoid hospitalization.

Hypothesis:
We assessed whether a high initial urine sodium (Na) after an intravenous diuretic bolus would predict net urine output > 1 liter after 3 hours of diuretic infusion, performed in an ACTIVE (Ambulatory Cardiac Triage, InterVention, and Education) unit where a nurse and pharmacist also provided heart failure education.

Methods and Results:
The unit accepted patients with chronic heart failure referred with symptomatic fluid overload without severe decompensation, and prescribed loop diuretic bolus and infusion dosed from an internal algorithm based on daily oral dose. Urine output was > 1 liter after 3 hours in 77% of patients with urine Na response > 100 mmol/L, in 69% with urine Na 61-100, and only 23% with initial urine Na < 60 mmol/L. Baseline renal function was better in patients with higher urine Na after diuretic therapy.

Conclusion:
In conclusion, we can anticipate at least 1 liter diuresis in most patients with initial urine Na > 60 mmol/L after bolus diuretic. Patients with urine Na > 100 also have significantly lower 30 day ED and admission rates after outpatient diuretic infusion. Patients with low urine Na response may still have diuresis but may need more prolonged intervention or revision of goals of care.
Abstract 16446: Discordant Imaging Results in Patients Referred for Mitral Valve Surgery: What Can the Left Ventricle Tell Us?
Authors: Uretsky Seth , Gillam Linda D , Cohen Randy , Argulian Edgar , Koulogiannis Konstantinos , Jang James J , Subero Marjorie , Marcoff Leo , Chaudhry Farooq A , Wolff Steven D
Published: July 2021

Introduction:
The assessment of mitral regurgitation (MR) severity is often based on echocardiographic (Echo) criteria and clinical assessment. Recently MRI has been used to quantify MR. In clinical practice these imaging modalities can be discordant. In an ongoing multicenter prospective study, we evaluated the degree of discordance between Echo and MRI in patients with isolated MR. We also correlated the pre-surgical MR volume (MRVol) to the decrease in left ventricular end-diastolic volume (LV EDV) after successful mitral valve surgery (MVS).

Hypothesis:
Does the post-surgical change in LV EDV correlate with MRVol?

Methods:
The study included 96 pts (60 ± 14yrs, male 57%) with isolated MR (19 fxnl, 43 degen, 34 other). 31 pts had isolated MVS. Each pt had MRVol quantified using Echo (PISA method) and MRI (LV stroke volume - forward flow). MR severity was categorized as mild <30ml, moderate 30-59ml, or severe ≥60ml. Patients who had MVS (10 MVR, 21 MV repair) also had MRI 4 months following surgery. The pre-surgical MRVol was correlated with the postoperative decrease in LV EDV.

Results:
MRI and Echo estimates of mitral RVol. were correlated (y=0.6x + 26) (r=0.6, p <0.001). There was agreement in 51/96 (53%) when using the categories of mild, moderate and severe, and 67/96 (70%) when comparing severe vs. not severe. The modalities agreed in only 11/31 (33%) pts referred for MVS. Post-surgery MRI was performed in 21 pts. While there was good correlation between MRI MRVol and post surgical negative remodeling (r=0.8, p<0.001), there was no correlation between Echo MRVol and post surgical negative remodeling (r =0.1, p =0.5) (figure).

Conclusions:
There is often discordance between Echo PISA and MRI when quantifying MRVol even in patients referred for surgery. To the degree that post-surgical LV remodeling reflects the reduction in LV volume overload achieved with successful MVS, these data suggest that MRVol quantified by MRI may be more accurate than MRVol quantified by Echo PISA.
Abstract 16492: A Common Gene Network Governs the Cellular Phenotypes in Acute Aortic Dissection
Authors: Ohno Satoko , Aoki Hiroki , Nishihara Michihide , Furusho Aya , Hirakata Saki , Nishida Norifumi , Ito Sohei , Yasukawa Hideo , Fukumoto Yoshihiro
Published: July 2021

Acute aortic dissection (AAD) is a common disease with sudden onset and high mortality, for which pathogenesis is largely unknown. To better understand AAD pathogenesis, we examined three mouse models of AAD; knockout mice for tenascin C, an extracellular glycoprotein that is secreted by vascular smooth muscle cells (VSMCs), macrophage-specific knockout of SOCS3 (mSOCS3-KO), a negative regulator of JAK/STAT signaling, and infusion of beta-aminopropionitrile, that blocks crosslinking of elastin and collagens. All of three models develop AAD upon the continuous infusion of angiotensin II (AngII). We performed transcriptome analyses at the early time point of AngII infusion when the aortic structure showed no obvious abnormality. Interestingly, the gene expression patterns showed common changes; induction of proinflammatory molecules and cell cycle machinery, and suppression of the structural extracellular matrix (ECM) and cytoskeletal molecules of VSMCs. Such a pattern is consistent with that in human AAD as previously reported. We performed detailed analysis in mSOCS3-KO. Bayesian network model revealed that upregulation of cell cycle machinery precedes other changes in the gene expression. Cell cycle analyses using Ki67 staining and BrdU uptake assay showed that AngII caused proliferative response before AAD development both in macrophages and in VSMCs, indicating the macrophage-VSMC interaction. In addition, the proliferative response of macrophages was associated with the preferential differentiation into the proinflammatory M1 phenotype as determined by the high expression of Ly6C. Our findings showed a gene expression network of AAD that is common to human and mouse models. The findings in mouse models suggest that cell cycle activation precedes both the proinflammatory response in macrophages and the functional deterioration of VSMCs, which in turn would weaken the aortic wall strength. In addition, tissue-specific knockout studies revealed that interactions between macrophages and VSMCs underlie the gene expression network in AAD. Deciphering such cellular interactions and gene expressions would lead to better understanding of this fatal disease.
Abstract 16532: Impact of Systolic Blood Pressure on Cardiovascular Disease in a Chinese Population: A Mendelian Randomization Study
Authors: Clarke Robert , Li Liming , Bennett Derrick , Millwood Iona Y , Walters Robin G , Guo Yu , Bian Zheng , Peto Richard , Collins Rory , Parish Sarah , Chen Zhengming M
Published: July 2021

Aims:
To investigate the quantitative importance of systolic blood pressure (SBP) for cardiovascular disease using a Mendelian randomization analysis and compare the risk associations with equivalent differences in standard measures of SBP after correction for regression dilution.

Methods:
In the China Kadoorie Biobank prospective study, 82,373 unrelated adults aged 30-79 years had SBP recorded and were genotyped for 384 candidate SNPs, including 32 SNPs previously associated with blood pressure. These SNPs were combined to generate a genetic score for SBP (GS-SBP) and estimate the associated relative risks (RR) and 95% confidence intervals (CI) of major cardiovascular events (stroke, and non-fatal MI or IHD death). The results were compared with the RRs for 20 mmHg higher SBP before and after correction for regression dilution (basal or usual SBP).The correlation coefficient between replicate measurements of SBP between baseline and a re-survey after 3 years was 0.6 and was used to correct for regression dilution.

Results:
The overall mean (SD) age at survey was 51 (10.7) years and mean (SD) SBP was 131.9 (22.2) mmHg, but only 4.8% reported use of any anti-hypertensive treatment. Overall, there was a 5 mmHg difference in the mean SBP between the top and bottom fifths of the GS-SBP. After adjustment for regression dilution, each 20 mmHg higher usual SBP was associated with RRs of 1.78, 2.45, 1.61, and 1.84 for ischaemic stroke, haemorrhagic stroke, non-fatal MI or IHD death and major cardiovascular events, respectively (Table). For GS-SBP, the corresponding RRs were much more extreme, being 2.48, 2.85, 1.85 and 2.69, respectively.

Conclusions:
This Mendelian randomization study demonstrates that the effects of long-term differences in SBP for risk of major cardiovascular events in this largely untreated population were almost 50% greater than those estimated for standard measures of SBP after correction for regression dilution.
Abstract 16544: Focal Fibrosis Predicts Monomorphic VT but Not Polymorphic VT or VF in Nonischemic Dilated Cardiomyopathy
Authors: Piers Sebastiaan R , Everaerts Kimberly , Van der Geest Rob , Hazebroek Mark R , Venlet Jeroen , Siebelink Hans-Marc , Pison Laurent , Schalij Martin J , Bekkers Sebastiaan C , Heymans Stephane , Zeppenfeld Katja
Published: July 2021

Purpose:
This study aimed to analyze the effect of focal myocardial fibrosis, assessed by late gadolinium enhancement MRI (LGE-MRI), on the occurrence and type of ventricular arrhythmia in patients with nonischemic dilated cardiomyopathy (NIDCM).

Methods:
We included consecutive patients with NIDCM who underwent LGE-MRI before implantable cardioverter-defibrillator (ICD) implantation at two centers. LGE was defined by signal intensity ≥35% of maximal signal intensity and subdivided into core and border zone (≥50% and 35-50% of maximal signal intensity, respectively), and according to (non)basal location and transmurality. ICD recordings and 12-lead ECGs were reviewed to determine the occurrence and type of ventricular arrhythmia during follow-up.

Results:
Of all 87 patients (62% male, age 56±13 years, LVEF 29±12%), 55 patients (63%) had LGE (median 6.3g, IQR 0.0-13.8g). During a median follow-up of 45 months (interquartile range, 23-67), monomorphic VT occurred in 18 (21%) patients, and polymorphic VT/VF in 10 (11%). LGE predicted monomorphic VT (Log-rank, p<0.001), but not polymorphic VT/VF (Log-rank, p=0.40). The optimal cut-off value for LGE to predict monomorphic VT was 7.2 grams (area under curve 0.84). Features associated with high risk for monomorphic VT were core extent, location in basal segments and area with 51-75% transmurality.

Conclusion:
Focal fibrosis assessed by LGE-MRI predicts monomorphic VT, but not polymorphic VT/VF. The risk for monomorphic VT was particularly high when the LGE extent was ≥7.2 grams. The differences in underlying substrate and associated types of arrhythmia may have important implications for risk stratification and therapeutic interventions in patients with NIDCM.
Abstract 16585: Prediction of Atherosclerotic Cardiovascular Disease Mortality in a Nationally Representative Cohort Using Set of Risk Factors From Pooled Cohort Risk Equations
Authors: Zhang Zefeng , Yang Quanhe , Bardenheier Barbara , Gillespie Cathleen , Bowman Barbara
Published: July 2021

Introduction:
The American College of Cardiology/American Heart Association Pooled Cohort risk equations were developed to estimate atherosclerotic cardiovascular disease (ASCVD) risk. It is unclear if the set of risk factors might predict ASCVD mortality in a nationally representative cohort.

Hypothesis:
We assessed the performance of the set of risk factors developed by the Pooled Cohort equations in the prediction of ASCVD mortality by sex and race-ethnicity.

Methods:
We used the Third National Health and Nutrition Examination Survey Linked Mortality File (NHANES III 1988-2006, n=7,042) and included participants 40-79 years of age without CVD at baseline. We used Cox proportional hazard models to estimate the predicted probability of ASCVD death at 10-year by sex and race-ethnicity (non-Hispanic white (NHW), non-Hispanic black (NHB), and Mexican American (MA)). We calculated the discrimination and calibration for each sex-race-ethnicity model.

Results:
We documented 409 ASCVD deaths during 62,335 person years of follow-up (212 men and 197 women). The Pooled Cohort equations’ set of risk factors demonstrated moderate discrimination ability for ASCVD mortality with modified c-statistics of 0.658 (95% CI: 0.602-0.713), 0.661 (0.589-0.732), and 0.703 (0.624-0.782) for NHW, NHB and MA men respectively. The corresponding c-statistics for women were 0.695 (0.631-0.760), 0.695 (0.624-0.765), and 0.687 (0.588-0.786). Modified Hosmer-Lemeshow χ
2
suggested adequate calibration for NHW men and women (p-value 0.13 and 0.06 respectively). The calibration was borderline adequate for NHB women with p-value 0.04, and inadequate for MA men and women with p-value <0.001 and 0.004 respectively. The moderate discrimination and inadequate calibration for some prediction models might be partly due to the limited sample size.

Conclusions:
In conclusion, in this nationally representative cohort, the set of risk factors from the Pooled Cohort equations perform adequately to predict 10-year ASCVD mortality for NHW men and women with observed and predicted 10-year ASCVD deaths being similar, and demonstrated moderate discrimination for all sex-race/ethnicity groups.
Abstract 16593: Endocytosis Pathway of Kv1.5 Channels in Atrial Cardiomyocytes
Authors: Barbier Camille , Eichel Catherine , Louault Florent , Rucker-Martin Catherine , Coulombe Alain , Hatem Stéphane , Balse Elise
Published: July 2021

Trafficking of ion channels in cardiomyocytes is a highly dynamic process which is determinant for shaping action potential (AP). In this study, we focused on the dynamic of Kv1.5 channel which carry the atria-specific potassium outward current involved in the repolarisation of the AP.

We first investigated the endocytosis pathway for Kv1.5 channels in the atria.

High resolution 3-D microscopy revealed that Kv1.5 channels are associated with clathrin vesicles in atrial myocytes but not with caveolin. Electron microscopy showed that vesicles are found both at the lateral sarcolemma and at the intercalated disc. Blockade of the clathrin pathway using sucrose or SiRNA induced an increase in IKur recorded by whole-cell patch-clamp and an accumulation of Kv1.5 channels at the sarcolemma as shown by biotinylation assay. Clathrin blockade also increased fluorescence recovery after photo bleaching of Kv1.5 channels. Altogether, these data show that Kv1.5 channels are internalized through the clathrin pathway.

TIRF microscopy approach was used to follow eGFPKv1.5-Kv1.5 channels in living cells and to establish their dynamic in control and clathrin-blocked myocytes. Blockade of the clathrin pathway leads to a global increase of Kv1.5 channels at the membrane. Particle analysis revealed an accumulation of the channels into clusters and their stabilisation at the membrane.

Our objective now is to investigate the involvement of the cytoskeleton in Kv1.5 channels endocytosis by using dyes staining tubulin or actin in live cells; and the fate of internalized channels at different time points by co-immunostainings with antibodies directed against the different endosomes.

In conclusion, we have identified the clathrin pathway as the internalization route for Kv1.5 channel, in atrial myocytes. The blockade of this pathway modifies Kv1.5 channels dynamic at the membrane. Future work will be conducted to further investigate dynamic and fate of this atria-specific channel. This study should help understanding the constitution of the sub-membrane reservoir of repolarization that we previously described (Balse E., et al. 2009, PNAS).
Abstract 16602: Pulmonary Vascular Response to Metaboreflex Stimulation During Submaximal Exercise in Heart Failure
Authors: VanIterson Erik H , Snyder Eric M , Johnson Bruce D , Olson Thomas P
Published: July 2021

Introduction:
Neural feedback from skeletal muscle during exercise contributes to changes in pulmonary pressures in healthy individuals. Heart failure patients (HF) often develop pulmonary hypertension; however, the relationship between muscle afferent feedback and the pulmonary vasculature in HF remains unclear.

Hypothesis:
We examined the influence of metaboreceptor stimulation on pulmonary vascular capacitance using a validated non-invasive gas exchange equivalent (GX
CAP
) in HF.

Methods:
Eleven HF patients (age 51±5 yrs; EF, 32±3%; NYHA class, 1.6±0.2) and 11 controls (CTL; age 43±3 yrs) completed 3 cycling session (4-min at 60% of peak oxygen consumption, VO
2
). Session one: baseline control trial. Sessions 2 and 3: bilateral upper-thigh tourniquets inflated suprasystolic for 2 min at end-exercise (regional circulatory occlusion, RCO) with or without addition of inspired CO
2
to maintain end-exercise end-tidal CO
2
(P
ET
CO
2
) (RCO+CO
2
) (randomized). Rest, exercise, and recovery heart rate (HR), P
ET
CO
2
, and VO
2
were measured. O
2
pulse (VO
2
/HR) and GX
CAP
(O
2
pulseхP
ET
CO
2
) were calculated.

Results:
During all conditions at end-exercise, HF demonstrated significantly lower GX
CAP
compared to CTL (p<0.01). Percent change in GX
CAP
from end-exercise to 2 min post-exercise was attenuated in HF compared to CTL (41±5% vs 64±1%, respectively, p<0.01) during the baseline trial. During RCO, HF had a 55±6% reduction in GX
CAP
from end-exercise compared to 77±2% in CTL (p<0.01). During RCO+CO
2
, HF had a 49±4% reduction in GX
CAP
from end-exercise compared to 69±2% in CTL (p<0.01). GX
CAP
was similar between sessions within HF. The CTL group demonstrated an attenuated return of GX
CAP
during RCO compared to both baseline and RCO+CO
2
(p<0.01) with no difference between baseline and RCO+CO
2
.

Conclusion:
These data suggest the exercise mediated rise and post-exercise recovery of pulmonary vascular capacitance are attenuated in HF during constant-load submaximal exercise compared to CTL. Additionally, our data confirm previous reports that locomotor muscle afferent feedback influences pulmonary vascular capacitance in CTL; however, this model of locomotor muscle metaboreflex stimulation appears to a differential response in HF compared to CTL.
Abstract 16616: Echocardiography Reveals Biventricular Abnormalities in Presymptomatic Phospholamban p.Arg14del Mutation Carriers
Authors: te Rijdt Wouter P , Hummel Yoran M , van Tintelen J. Peter , de Boer Rudolf A , van den Berg Maarten P
Published: July 2021

Introduction:
Echocardiographic myocardial deformation imaging is an emerging tool for assessing cardiac function and identifying preclinical cardiomyopathies. A large subset of our patients diagnosed with dilated cardiomyopathy (DCM) or arrhythmogenic right ventricular cardiomyopathy (ARVC) carry the pathogenic phospholamban (PLN) c.40_42delAGA (p.Arg14del) founder mutation. The natural course of these mutation carriers is characterized by a presymptomatic phase of variable length, after which many carriers progress to overt disease, manifesting as DCM and/or ARVC.

Objective:
To identify subclinical structural and functional cardiac abnormalities in presymptomatic carriers of an identical PLN p.Arg14del mutation using echocardiography including state-of-the-art tissue deformation imaging techniques.

Methods:
Twenty-eight presymptomatic PLN p.Arg14del mutation carriers (46% males; mean [±SD] age 33±11 years), identified by genetic cascade screening, and 28 healthy matched control subjects were included in this cross-sectional study. Both groups underwent comprehensive transthoracic echocardiography including LV and RV myocardial two-dimensional strain measurements. Global LV early diastolic tissue velocity (Global e’) and global longitudinal systolic strain (GLSS) were assessed from 12 LV segments and from 3 RV segments.

Results:
In the mutation carrier group, LV ejection fraction was preserved (59.0±5.2 vs. 58.8±5.3 (%), P=0.788). However, LV mass index was reduced (58.4±13.9 vs. 71.5±15.6 (g/m^2), P=0.002) and we also observed loss of diastolic function (LV early diastolic inflow 0.79±0.15 vs. 0.95±0.18 (m/sec), P=0.001; LV late diastolic inflow 0.52±0.13 vs. 0.60±0.13 (m/sec), P=0.031; Global e’ 6.7±1.3 vs. 7.4±1.2 (cm/s), P=0.081). In addition, RV GLSS was lower in mutation carriers compared with controls (25.4±4.6 vs. 31.4±4.9 (cm/s), P<0.001).

Conclusions:
Presymptomatic PLN p.Arg14del mutation carriers already showed slight but significant structural remodeling (reduced LV mass) as well as loss of LV diastolic function and RV systolic function. These findings support the concept of biventricular cardiomyopathy.
Abstract 16698: Comparison of Hospital Length of Stay Between Hospitalized Non-Valvular Atrial Fibrillation Patients Treated With Either Apixaban or Warfarin
Authors: Farr Amanda , Jing Yonghua , Johnston Stephen , Trocio Jeffrey , Singhal Shalabh , Graham John
Published: July 2021

Hospital length of stay (LOS) is an important cost driver for hospitals and payers alike. Hospitalized non-valvular atrial fibrillation (NVAF) patients treated with apixaban may have shorter LOS than those treated with warfarin because of the absence of need for INR monitoring in apixaban. Thus, this study compared LOS between hospitalized NVAF patients treated with either apixaban or warfarin.

This was a retrospective, observational cohort study based on a large U.S. database including diagnosis, procedure, and drug administration information from over 600 acute-care hospitals. Patients selected for study were aged ≥18 years and had a hospitalization record with an ICD-9-CM diagnosis code for atrial fibrillation (AF) in any position from Jan-1-2013 to Feb-28-2014 (index hospitalization). Patients with diagnoses indicative of rheumatic mitral valvular heart disease or a valve replacement procedure during index hospitalization were excluded. Patients were required to have been treated with either apixaban or warfarin, and not treated with rivaroxaban or dabigatran, during index hospitalization. Apixaban patients were propensity score (PS) matched to warfarin patients at a 1:1 ratio, using patient demographic/clinical and hospital characteristics. Study outcome was LOS, calculated as discharge date minus admission date; a sensitivity analysis calculated LOS as discharge date minus first anticoagulant administration date. Subanalyses were conducted among patients with a primary diagnosis of AF.

The study included 832 apixaban patients matched to 832 warfarin patients. Patients had a mean age of 74 years and 46% were female. Mean [standard deviation (SD)] and median LOS was significantly (P<0.001) shorter in apixaban patients (4.5 [4.2] and 3 days) than in warfarin patients (5.4 [5.0] and 4); results were consistent in sensitivity analyses of LOS after first anticoagulant administration date (2.8 [3.5] and 2 days for apixaban vs. 3.9 [3.9] and 3 for warfarin, P<0.001). Subanalyses yielded very similar results.

Among NVAF patients, apixaban treatment was associated with shorter hospital LOS when compared with warfarin treatment. These findings may have important clinical and economic implications for hospitals, payers, and patients.
Abstract 16709: Contrasting Influences of Renal Function on Blood Pressure and HbA1c Reductions With Empagliflozin in Patients With Type 2 Diabetes and Hypertension
Authors: Cherney David , Cooper Mark , Tikkanen Ilkka , Crowe Susanne , Johansen Odd Erik , Lund Søren S , Woerle Hans J , Broedl Uli C , Hach Thomas
Published: July 2021

The sodium glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces HbA1c, weight and blood pressure (BP) in patients with type 2 diabetes (T2D). While glucose lowering with EMPA is dependent on renal function, the impact of chronic kidney disease (CKD) on BP reduction with EMPA is less well understood. Our aim was to determine if impaired renal function attenuates antihypertensive effects of EMPA.

A Phase III randomized placebo (PBO)-controlled trial (EMPA-REG BP™) investigated the efficacy and safety of EMPA in patients with T2D and hypertension (defined as mean seated office systolic BP [SBP] 130-159 mmHg and diastolic BP [DBP] 80-99 mmHg at screening). Patients (mean [SD] age 60.2 [9.0] years, HbA1c 7.90 [0.74] %, 24-hour SBP 131.4 [12.3] and 24-hour DBP 75.0 [7.8] mmHg) received EMPA 10 mg (n=276), EMPA 25 mg (n=276) or PBO (n=271) once daily for 12 weeks. We assessed changes from baseline in mean ambulatory 24-hour SBP and HbA1c in subgroups by baseline eGFR (MDRD equation), adjusting for differences in baseline mean 24-hour SBP (for SBP analyses only), HbA1c, region, number of antihypertensive medications, treatment, eGFR and treatment by eGFR interaction between groups.

In patients with normal renal function, or stage 2 or 3 CKD, EMPA significantly reduced HbA1c and mean 24-hour SBP vs PBO (Table). As expected, PBO-corrected HbA1c reductions with EMPA appeared to decrease with decreasing eGFR (Table). In contrast, PBO-corrected reductions in mean 24-hour SBP with EMPA mostly appeared to increase with decreasing eGFR (Table).

Unlike HbA1c, mean 24-hour SBP reductions with EMPA in patients with T2D and hypertension appear to be greater in patients with lower eGFR, indicating that SBP modulation with EMPA may involve pathways other than urinary glucose excretion such as diuretic effects, weight loss, improved glycemic control, reduced arterial stiffness or direct vascular effects.
Abstract 16714: Real-World Cost of All-Cause Hospitalizations Over a 12-Month Period After Acute Venous Thromboembolism
Authors: Shorr Andrew F , Johnston Stephen , Jing Yonghua , Schaiff Robyn A , Trocio Jeffrey , Thomson Erin , Juneau Paul , Graham John
Published: July 2021

Recent clinical trial data have shown that newer oral anticoagulants may reduce all-cause hospitalizations in patients with venous thromboembolism (VTE) who complete anticoagulation therapy for 6-12 months. To understand the potential cost implications of such hospitalization reductions, this study sought to quantify the real-world cost of all-cause hospitalizations over a 12-month period after acute VTE.

This was a retrospective cohort study using U.S. health insurance claims data. Patients included in the study were aged ≥18 years, had experienced a non-fatal hospitalization or ED visit with a principal diagnosis of VTE between 1-Jan-2007 and 31-Mar-2013 (first visit=index) and had ≥1 claim for anticoagulation (warfarin, enoxaparin, rivaroxaban) or placement of an inferior vena cava filter ≤30 days after index. For up-to one year after discharge from the hospitalization or ED visit for acute VTE, patients were followed to identify the occurrence and costs of all-cause hospitalizations. Multivariable regressions were used to compare per-patient per-month (PPPM) total healthcare costs between patients with vs. without a hospitalization during follow-up.

The final cohort included 123,665 patients (mean age 59 years, 50% male). During an overall mean follow-up of 284 days after discharge from the acute VTE event, 33,843 patients were hospitalized at least once for any cause within 1 year and 37% of these hospitalized patients had at least one hospitalization for VTE. Among patients who were hospitalized, mean (standard deviation) PPPM hospital length of stay and PPPM costs for hospitalizations were 1.4 (2.8) and $5,800 ($14,723) at 1 year. Adjusted incremental PPPM differences in total healthcare costs between patients with vs. without a hospitalization during the 1-year follow-up were $ $4,808 (P<0.001).

Conclusion:
Hospitalizations within 1 year after acute VTE are common and costly. VTE treatments which reduce hospitalizations after acute VTE may confer substantial cost offsets.
Abstract 16717: My Unlimited Health Potential: 12 Month Effect of Participation in a Worksite Lifestyle Intervention Program on Significant Weight Loss and Eligibility Criteria for Bariatric Surgery Among High Risk Individuals
Authors: Shaharyar Sameer , Roberson Lara , Aneni Ehimen , Rouseff Maribeth , Tran Thinh , Guzman Henry , Das Sankalp , Brown Doris , Santaigo-Charles Joann , Ochoa Teresa , Mora Joseph , Castillo Beatriz , Veledar Emir , Feldman Theodore , Agatston Arthur , Post Janisse , Nasir Khurram
Published: July 2021

BACKGROUND:
Bariatric surgery among the morbidly obese is recommended as an option to mitigate future risk of cardiovascular disease, diabetes and hypertension. To date there is little evidence on the effect of extensive lifestyle interventions among these high-risk groups in reducing the need for such procedures in extended periods.

METHODS:
The purpose of the present study is assess efficacy of an intensive lifestyle workplace intervention on significant body weight across the spectrum of obesity in a worksite wellness program, called “My Unlimited Potential (MyUP)” conducted at Baptist Health South Florida. Changes in BMI are being measured from baseline to 12 months follow up, along with corresponding improvements in cardio-metabolic risk. In addition, the decrease in participants meeting criteria for bariatric surgery over the study period is examined at 6 and 12 months. Bariatric surgery criteria were defined as BMI≥40 or BMI between 35 and 40 and at least one of the following co-morbidities: diabetes, hypertension, or high cholesterol.

RESULTS:
The study population consisted of 272 individuals (48±9 years, 78% female) with BMI≥27 at baseline. Complete data at 12-month follow up was available for 141 individuals (52%). A total of 21(14%) and 14 (10%) participants had lost at least 10 % of their body weight by 6 months and 12 months respectively. Forty-six participants (32%) initially met criteria for bariatric surgery. At six month follow-up 43% (20 of 46, p<0.001) of these candidates no longer needed bariatric surgery. Of these, 80% (16 out of 20) retained their weight loss at 12 months.

CONCLUSIONS:
This worksite wellness program effectively obviated the need for bariatric surgery in approximately half of those who were initially eligible at 1 year of follow up. Replication of this program with a larger cohort with stricter attention to attrition is needed to asses the utility of our program and its implications as a larger corporate wellness strategy.
Abstract 16726: Dynamic Analysis of the Tricuspid Annulus -Does Non Planarity of the Annulus Matter?
Authors: Addetia Karima , Muraru Denisa , Veronesi Federico , Maffessanti Francesco , Mor-Avi Victor , Yamat Megan , Weinert Lynn , Badano Luigi P , Lang Roberto M
Published: July 2021

Introduction:
Surgical decision-making on the tricuspid valve (TV) hinges on accurate measurements of the tricuspid annulus (TA). 3D echocardiography is more accurate than 2D for dynamic measurement of TA size due to TA non-planarity. Multiplanar reconstruction (MPR) of 3D datasets is easily performed on ultrasound machines but results in inconsistent measurements of minimum and maximum TA size. We developed an alternative method for dynamic TA measurement that accounts for TA non-planarity, to determine if this approach would yield different annulus sizes compared to the MPR method.

Methods:
51 normal subjects underwent 3D TTE of the TA (Philips). MPR measurements of the TA were made on a plane passing through 2 pairs of hinge points identified in orthogonal apical views (QLAB, fig.A). The alternative approach used custom software (CS) that initialized TA hinge points in mid-systole (MS) in multiple rotated planes, following the non-planar shape of the TA (fig. B); these were then tracked throughout the cardiac cycle. TA area, antero-posterior and septal-lateral dimensions were measured at end-diastole (ED, TV closure), MS and end-systole (ES, prior to TV opening), and compared between approaches.

Results:
MPR measurements showed minimum TA size at ED or MS. In contrast, the CS approach resulted in significantly larger measurements and showed minimum TA size at ES (Table). Careful review revealed that in many patients the annular plane in which MPR measurements were made cut through parts of the right atrial (RA) walls.

Conclusions:
MPR-based TA size may be underestimated because this approach does not account for TA non-planarity, partially identifying RA walls as annular boundary, resulting in a minimum at ED, when the RA is smallest. Alternative software approaches that account for TA non-planarity should be explored with surgical validation and are required to accurately assess TA size and dynamics. This may have implications on TV annuloplasty planning.
Abstract 16730: Prognostic Biomarker for Prediction of Sinus Rhythm Maintenance, Stroke and Long-Term Survival Following Successful Electrical Cardioversion of Non-Valvular Atrial Fibrillation:
The Role of Left Atrial Appendage Flow
Authors: Melduni Rowlens M , Roman Jorge , Lee Hon-Chi , Friedman Paul A , Malouf Joseph F , White Roger D , Hodge David O , Jean Nathalie , Bruce Charles J , Munger Thomas M , Gersh Bernard J , Ammash Naser M
Published: July 2021

Introduction:
Left atrial appendage (LAA) flow depends largely on left ventricular compliance and may play a role in mediating the regulation of left atrial volume-pressure relationships.

Hypothesis:
We hypothesize that LAA emptying flow velocity (LAAEV) is a predictive factor of long-term outcomes (e.g. recurrent AF, stroke, and survival) after cardioversion for non-valvular AF.

Method:
We identified 3,251 consecutive patients with non-valvular AF who underwent successful TEE-guided electrical cardioversion (ECV) at our institution between May 2000 and March 2012. Successful ECV was defined as sinus rhythm at time of discharge from the cardioversion unit. Patients were monitored following their ECV procedure for first documentation of recurrent AF, stroke or death. Multivariate Cox proportional hazards models were used to identify independent predictors of long-term outcomes. Patients with >= moderate valvular regurgitation or stenosis were excluded.

Results:
Among the 3,251 patients who were successfully cardioverted to sinus rhythm, the mean (±SD) LAAEV was 38.43±23 cm/s and the median was 33 cm/s, (interquartile range [IQR], 20-50). Patients with LAAEV <=33 cm/s had higher CHA
2
DS
2
-VASc score (2.6±1.2 vs. 1.9±1.3,
P
=.009), larger LAVI (52.0±20.9 cc/m
2
vs. 43.3±13.6 cc/m
2
,
P
<.001) than those with LAAEV >33 cm/s. Pre or post-procedure antiarrhythmic drug use was similar between the two groups. During 1-year follow-up, patients with LAAEV <=33 cm/s had significantly higher rate of AF recurrence than those with LAAEV >33 cm/s (55% vs 45%,
P
<.001). Likewise, during a mean follow-up of 4.9±3.6 years, similar patterns in 5-year rates were observed for first recurrence of AF (81% vs 73%,
P
<.001), stroke (7% vs 4%,
P
=.003) and mortality (31% vs 23%,
P
<.001) for LAAEV <=33 vs > 33cm/s, respectively. Stepwise multivariate Cox regression analysis revealed that LAAEV <=33 cm/s, age, CHA
2
DS
2
-VASc score were independent predictors of AF recurrence, stroke and mortality.

Conclusions:
LAA emptying flow velocity is an effective and convenient method for risk stratification of patients undergoing cardioversion for AF. Our data showed that patients with reduced LAAEV have an increased risk for AF recurrence, stroke and death following electrical cardioversion.
Abstract 16738: Correlation Between Appropriate Use of Coronary CT Angiography and Downstream Resource Utilization
Authors: Chinnaiyan Kavitha , Hickman Leaden , Boura Judith A , DePetris Ann M , Peyser Patricia , Raff Gilbert , Nallamothu Brahmajee
Published: July 2021

Introduction:
Limited data exist regarding the correlation between the appropriateness of use of coronary CT angiography (CTA) and downstream resource utilization (RU).

Methods:
Data from the Advanced Cardiovascular Imaging Consortium, a statewide CTA registry were linked to Blue Cross Blue Shield of Michigan claims data. Based on the 2010 appropriate use criteria, the group was divided into: appropriate (A), inappropriate (I), uncertain (U) and unclassifiable (UC). CTA findings and RU (hospitalizations, invasive angiography, revascularizations, stress testing) at 1 year were compared.

Results:
The study group consisted of 2307 patients (A =1582, I = 276, U = 195 and UC = 254). The most common indication among the I group was use of coronary CTA for CAD screening (32%). Compared to the A group, patients in the I group were older and more often male, and had higher prevalence both nonobstructive (<50% stenosis, 69.2% vs. 54.1%, p<0.0001) and obstructive (≥50% stenosis, 27.8% vs. 19.3%, p<0.0001) CAD. No significant difference was noted between the A and I groups with respect to overall downstream resource utilization (46.9% vs. 44.6%, p = 0.47), invasive procedures (15% vs. 15.2%, p = 0.94) or noninvasive testing (43.1% vs. 40.6%, p = 0.44). On multivariate analysis among all patients, the finding of obstructive CAD was the strongest predictor of overall resource utilization (OR 5.33 [95% CI 3.51-8.10]) followed by acute presentation (OR 2.1 [95% CI 1.48-2.98]) ; inappropriate use was not a significant predictor (OR 0.78 [95% CI 0.51-1.19]).

Conclusions:
In this population-based cohort, 68.5% of patients were appropriately referred for CTA. Appropriate use did not correlate with downstream resource utilization events, which were driven strongly by CTA findings. Additionally, patients deemed inappropriate for CTA had higher burden of CAD, with implications for early detection and prognosis in these patients. Further studies are needed to adjudicate appropriateness of use of coronary CTA.
Abstract 16744: Impact of Wireless Pulmonary Artery Pressure Monitoring on Heart Failure Hospitalizations and All-Cause 30-Day Readmissions in Medicare-Eligible Patients With NYHA Class III Heart Failure: Results From the CHAMPION Trial
Authors: Adamson Philip B , Abraham William T , Bauman Jordan , Yadav Jay
Published: July 2021

Introduction:
Heart failure (HF) is the most frequent discharge diagnosis for hospitalized Medicare beneficiaries. Readmission after a HF hospitalization (HFH) is an important metric for quality of care. Under the Hospital Readmissions Reduction Program (HRRP), hospitals with excess all-cause 30-day readmissions may be penalized for inadequate quality of care. Results from the CHAMPION trial confirmed that HF management using pulmonary artery pressure (PAP) monitoring from an implanted sensor in patients with NYHA Class III HF reduced HFH rates compared to standard management. However, the impact of this strategy on HFH rates and all-cause 30-day readmissions in Medicare-eligible patients is unknown.

Methods:
Retrospective analyses of patients 65 years or older at baseline in the CHAMPION trial were performed. HFH rates and 30-day readmissions in this subgroup were compared. Excess readmission ratios reported by the HRRP were then compared with the CHAMPION readmission ratio resulting from PAP monitoring.

Results:
245 patients in CHAMPION (45%) were 65 years or older at the time of PA sensor implantation (120 in the Treatment group and 125 in the Control group). Patients in the Treatment group managed with PAP monitoring had a significantly lower HFH rate (60 HFH, 0.34/year) compared to the Control group (117 HFH, 0.67/year) (IRR 0.51, 95% CI 0.37-0.70, p<0.0001). The Treatment group had a significantly reduced 30-day readmissions rate (13 readmissions, 0.07/year) compared to the Control group (31 readmissions, 0.18/year) (IRR 0.42, 95% CI 0.20-0.82, p=0.006). Using index HFH as the unit of observation for 30-day readmissions, the Treatment group ratio (13 readmissions/56 index HFH, 23.2%) was lower than the Control group ratio (31 readmissions/99 index HFH, 31.3%). PAP monitoring resulted in a CHAMPION readmission ratio (23.2%/31.3%, 0.74) that was lower than all hospital excess readmission ratios reported in the 2011 HRRP dataset.

Conclusions:
HF management incorporating PAP monitoring significantly reduced HFH rates and all cause 30-day readmissions in Medicare-eligible patients. Adoption of this treatment strategy at hospitals struggling with HFH and 30-day readmissions could help address an unmet need within the US health care system.
Abstract 16758: Cardiosphere Derived Cells From Pediatric End-Stage Heart Failure Patients Have Enhanced Functional Activity Due to the Heat Shock Response Regulating the Secretome
Authors: Sharma Sudhish , MIshra Rachana , Simpson David , Colletti Evan J , Deshmukh savitha , Chen Ling , Wehman Brody P , Kaushal shalesh , Kaushal Sunjay
Published: July 2021

Rationale:
Results from pre-clinical studies and a Phase I clinical study demonstrates promising functional recovery by adult cardiosphere derived cells (CDCs) to repair damaged myocardium. We have previously demonstrated that age regulates the functional recovery of neonatal CDCs due to their more effective secretome. However, how advanced failure pediatric hearts regulate their derived CDC’s functional activity is still unknown.

Objective:
Our aim was to compare the functional potency between pediatric CDCs derived from normal myocardium of congenital heart disease (CHD) patients and from dysfunctional myocardium of pediatric end stage failing heart (ESHF) patients and determine the mechanisms involved.

Methods and Results:
ESHF derived hCDCs had a higher number of cardiac stem cells expressing c-kit+, Islet-1+, and Sca-1+. When transplanted in an infracted rodent model, ESHF derived hCDCs had a significantly higher preservation of ventricular function, prevented adverse remodeling, and enhanced angiogenesis when compared with CHD derived CDCs. The superior functional recovery of the ESHF derived hCDCs was mediated in part by increased SDF-1α and VEGF-A secretion which recruited more endogenous stem cells and proliferation of cardiomyocytes. The mechanism for the superior secretome is due to the heat shock response (HSR) which is supported by three lines of evidence. First, gain of function studies demonstrated that the HSR induced the low functioning CHD derived CDCs to significantly recover the injured myocardium to the same extent as ESHF derived CDCs. Secondly, loss-of function studies targeting the HSR down regulated the ability of the ESHF derived CDCs to functionally recover the injured myocardium. Finally, the HSR alone increased the number of the c-kit+ CSCs both in vitro and in vivo.

Conclusion:
These findings suggest that the HSR enhances the functional activity of ESHF derived CDCs by regulating their secretome.
Abstract 16763: Mechanical Circulatory Support Promotes Myocardial Nitric Oxide Signaling in Heart Failure Patients
Authors: Polhemus David J , Tao Ya-Xiong , Koenig Steven C , Prabhu Sumanth D , Lefer David
Published: July 2021

Introduction:
The integrity of the cardiovascular system is dependent on the continuous generation of nitric oxide (NO). Reduction in NO bioavailability is central to the development of cardiovascular disorders and patients with heart failure (HF) exhibit blunted endothelium-dependent flow-mediated dilation in indicating diminished NO release. We have previously reported that patients with heart failure have marked reductions in circulating NO metabolites and that NO-based therapies significantly reverse left ventricular (LV) dysfunction in preclinical animal models of HF.

Methods:
Plasma and left ventricular (LV) tissue were collected in HF patients (n=10) at the time of left ventricular assist device (LVAD) implantation. Plasma and LV tissue were again collected in the same 10 patients at the time of cardiac transplantation. Plasma and cardiac nitrite concentrations were determined by ion chromatography methods and nitrosylated protein (RXNO) levels were measured by chemiluminescence detection. Cyclic guanosine 5’-monophosphate (cGMP) was analyzed using radioimmunoassay technique.

Results:
Results: Following LVAD implantation, RXNO (NO-bound protein) levels were significantly elevated in both circulation and in the LV (10.2 nM vs. 33.3 nM, p < 0.05). Downstream NO signaling activates soluble guanylyl cyclase to form cGMP. Interestingly, LV cGMP levels were significantly augmented post-LVAD implantation (p<0.01). In contrast, plasma and cardiac nitrite (NO2) levels remained unchanged.

Conclusions:
These data strongly suggest that cardiovascular remodeling accompanying LVAD implantation promotes endothelial nitric oxide synthase (eNOS) function and increases NO bioavailability and signaling.
Abstract 16784: Doxycycline Modulates Cardiomyocyte Remodeling in Light Chain-Induced Cardiac Amyloidosis
Authors: Wilson Richard M , Seldin David C , Sam Flora
Published: July 2021

Cardiac amyloidosis due to clonal immunoglobulin light chain (AL) is a potentially fatal disease. The mechanism(s) of cardiac dysfunction and myocardial damage caused by amyloid fibrils deposition represents the least understood aspect of amyloid pathology. Once diagnosed with heart failure (HF), the median survival of AL cardiac amyloidosis (ALCMP) patients is <6months if left untreated. However, only a minority of ALCMP patients are eligible for definitive therapy which includes autologous stem cell transplant and high dose melphalan. Despite this most patients continue to have evidence of HF and marked LVH on echocardiogram without regression even when this aggressive regimen is successful. Extracellular matrix turnover is implicated in the pathogenesis of ALCMP. Increased matrix metalloproteinase (MMP) activity may contribute to ALCMP. Doxycycline (DOX), an MMP inhibitor, reduces fibril formation and aggregates in murine models of AL and TTR amyloidosis. Autophagy plays a role in adverse cardiac remodeling, but it is unknown if LC deposition causes cardiomyocyte autophagy. We sought to test the hypothesis that DOX modulates LC-induced cardiac dysfunction and whether autophagy is part of the pathogenesis of the disease. Isolated adult rat cardiomyocytes were exposed to AL-LC (20μg/mL) or control LC (20μg/mL). MMP activities, proteins and intracellular signaling molecule expressions were measured. AL-LC increased MMP-2 (28±8%) and MMP-9 (25±6% P<0.05 for both) activities. U0126, a MEK/ERK inhibitor, blocked these increases, suggesting that the MAPK pathway is involved. DOX also decreased MMP-9 (-35±6%) and MMP-2 (-35±6% P<0.001 for both) activities vs AL-LC alone. AL-LC increased LC3II:LC3I protein expression ratio by 112±11% and ROS-regulated ATG4B expression by 156±13% (P<0.05 vs control for both). DOX decreased AL-LC induced LC3II:LC3I ratio by 42±8% (P=0.05) but did not significantly modulate ATG4B expression vs AL-LC. Thus, AL-LC induces autophagy and MMP-2 and MMP-9 activities in cardiomyocytes, which is modulated by DOX via a MEK/ERK pathway. Since ATG4B is not involved it may be independent of ROS. These pathways may provide potential targets for future therapeutic interventions for this near fatal form of cardiomyopathy.