bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11948: A Standardized Method to Isolate and Purify Cardiomyocytes from Individual Mouse Hearts Irrespective of Postnatal Age
Authors: Nicks Amy M , Holman Sara R , Chan Andrea Y , Pang Ching-ho J , Tsang Michael , Naqvi Nawazish , Husain Ahsan , Li Ming , Humphreys David T , Smith Nicola J , Iismaa Siiri E , Graham Robert M
Published: April 2024

Rational:
Primary cardiomyocytes (CMs) are invaluable for understanding postnatal heart development and elucidating disease mechanisms in genetic and pharmacological models, however, a method to obtain freshly purified CMs at any postnatal age, without the need for different age-dependent isolation procedures and cell culture, is lacking.

Objective:
To develop a standardized method that allows rapid isolation and purification of CMs in high yield and viability from individual neonatal, infant, and adult mice.

Methods and Results:
Using a novel
in situ
aortic cannulation procedure optimized to allow cannulation of even the very small vessel of neonates [postnatal day 0-2 (P0-2)], hearts of C57BL/6J mice were subjected to Langendorff retrograde perfusion and enzymatic digestion. After subsequent tissue disaggregation and filtration, CMs were isolated in high yield (1.55-2.2 x 10
6
CMs/heart) and viability (~78%). The larger size of infant (P10 and P13) and adult (P70), but not neonatal CMs, compared to non-myocytes, allowed their further enrichment by differential centrifugation, before purification at the bench by bead-based immunomagnetic cell separation. This involved depletion of endothelial cells (for infant and adult preparations) or non-myocytes (neonatal preparations). Together, these procedures resulted in highly purified CMs (~95%) from hearts of all ages within 1 hour. Moreover,
in situ
fixation immediately after tissue digestion via coronary perfusion, preserved the cytoarchitecture of isolated CMs (~94% rod-shaped CMs at all postnatal ages), allowing capture of spindle-shaped neonatal cells undergoing mitosis, as well as enabling accurate quantitation of CM area and nucleation state. RNA-sequencing of CMs purified from one P2 male and female heart per litter (n=4 litters) showed distinct clustering by litters rather than by sexes; a finding consistent with cardiac size and shape being indistinguishable between P2 male (n=6) and female (n=6) hearts as determined by micro-computed tomography (X-ray 3D imaging).

Conclusion:
The procedures developed here provide a universal protocol for the rapid purification of high-quality CMs from individual hearts at any postnatal age, even those of neonates.
Abstract 11969: Endocardial Viability Ratio is Associated With Survival in Advanced Heart Failure Patients
Authors: Ondigi Olivia , Bilchick Kenneth C , Stafford Patrick , Selinksi Christian , Harrison Kara , Jalenak Jay , Strickling Jarred , Shah Kajal P , Blazek Olivia , Mwansa Hunter , Breathett Khadijah , Johnson Amber , Mehta Nishaki , Kwon Younghoon , Sodhi Nishtha , Mazimba Sula
Published: April 2024

Introduction:
Myocardial oxygen supply is an important determinant of cardiac function. The Endocardial Viability Ratio (EVR), a measure of myocardial oxygen supply-demand balance, is calculated as a ratio of the diastolic pressure time index [(diastolic blood pressure - left ventricular end diastolic pressure) x (60 sec/heart rate - 0.2 sec)] and tension time index [systolic pressure x 0.2 sec]. We hypothesized that low EVR would be associated with adverse events in patients with heart failure (HF).

Methods:
EVR was calculated in the invasive arm of the ESCAPE trial in patients with available discharge blood pressure, pulmonary arterial wedge pressure, and heart rate as the ratio of the diastolic pressure time index (a measure of coronary blood supply) and tension time index (a measure of myocardial oxygen demand). Kaplan-Meier analysis and Cox proportional hazards regression was used to assess associations with EVR and a composite death endpoint including cardiac transplantation and left ventricular assist device implantation.

Results:
Among 143 patients (56.9 ± 13.3 years, 30.1% female), the median EVR was 1.168 (IQR 0.923-1.398). Survival during 180 days of follow-up was worse in patients with EVR below the median (p=0.0004) (Figure panel 1A). Among the 10 patients with EVR < 0.7, considered to represent subendocardial ischemia, 50% reached this endpoint within 100 days (p=0.01 versus remaining patients) (Figure 1B). An increase of 0.1 in EVR was associated with an 18% relative risk reduction for this endpoint (HR 0.82, 95% CI 0.74-0.91, p=0.0002), while an increase of 0.5 in EVR was associated with a 62% relative risk reduction (HR 0.38, 95% CI 0.22-0.64, p=0.002).

Conclusion:
Decreased EVR, a marker of myocardial oxygen supply, is associated with adverse events in advanced HF patients. Further studies on the prognostic utility of EVR in HF are needed.
Abstract 11973: Women Have Less Success of Thoracoscopic AF Ablation Than Men and Suffer More From Established Risk Factors
Authors: Wesselink Robin , Mossink Bente , Meulendijks Eva , van den Berg Nicoline , Neefs Jolien , Kawasaki Makiri , Piersma Femke , Al-Shama Rushd , de Vries Tim , Fabrizi Benedetta , Driessen Antoine , van Boven Wim Jan , de Groot Joris R
Published: April 2024

Background:
Women have more recurrent atrial fibrillation (AF) after AF ablation compared with men and are underrepresented in studies. What determines this worse outcome is incompletely understood.

Objective:
To explore the differential impact of established risk factors for AF recurrence in women and men.

Methods:
Consecutive patients (n=571) underwent thoracoscopic AF ablation. AF recurrence was defined as any atrial tachyarrhythmia >30s on ECG or Holter, during 2 years of follow-up with exclusion of the first 90 days blanking period. Holters were performed at 3, 6, 9, 12, 15, 18, and 24 months. Predictors of AF recurrence were assessed and compared by sex using the Cox proportional hazards model. Risk ratios (RR) of predictors for AF recurrence were assessed by sex.

Results:
At thoracoscopic ablation, women were older (63±8 vs. 59±9 years, p<0.001), had higher median [IQR] serum CRP (2.00 [0.90, 4.28] vs. 1.30 [0.65, 2.90] mg/ml p=0.006), but fewer cardiovascular risk factors (myocardial infarction (1.4% vs. 8.6%, p=0.03) and vascular disease (7.0% vs. 16.1%, p=0.01)). There was no difference in the prevalence of hypertension, heart failure, or diabetes mellitus. Freedom of AF recurrence until 2-year follow-up was 42.9% for women vs. 58.3% in men (p=0.002). The added risk for women was highest in patients with persistent AF (RR 1.4, p=0.001) (figure), aged >67y (RR 1.43, p=0.04), and moderate left atrial dilatation (>34 ml/m
2
) (RR 1.32, p=0.01).

Conclusion:
Persistent AF, old age, and moderate left atrial enlargement more negatively affect AF freedom in women than in men. Meanwhile, women had similar or fewer cardiovascular risk factors compared to men, underscoring sex as an important contributor to AF recurrence.
Abstract 11986: A Safety Study of Intermittent versus Continuous Inhaled NO Therapy in Spontaneously Breathing COVID-19 Patients: A Randomized Controlled Trial
Authors: Kamenshchikov Nikolay O , Kozlov Boris N , Dish Andrey Y , Podoksenov Yuri K , Anfinogenova Nina D , Boshchenko Alla A , Safaee Bijan , Berra Lorenzo
Published: April 2024

Introduction:
Nitric oxide (NO) inhalation (iNO) therapy has been approved as a salvage therapy in patients with acute respiratory distress syndrome. However, the optimal patterns of therapeutic administration and iNO efficacy in COVID-19 patients with hypoxemia have not been studied so far.

Hypothesis:
A combination of high-concentration intermittent iNO treatment with continuous low-concentration NO gas supplementation between therapeutic high-dose iNO sessions may be a safe approach in COVID-19 patients with hypoxemia compared with the high-dose spike therapy alone.

Methods:
A single-center randomized controlled trial examined the safety of administration of intermittent high-dose iNO therapy versus the intermittent therapy in the presence of continuous low-dose iNO in spontaneously breathing COVID-19 patients (www.clinicaltrials.gov #NCT04476992). The study comprised adult patients tested positive for the COVID-19 by RT-PCR, who required oxygen and was admitted to the respiratory hospital. After attrition, a total of 20 patients were enrolled and randomized to the group of intermittent high-dose iNO treatment combined with continuous low-dose NO supplementation (group 1) or the group of intermittent high-dose iNO treatment(group 2). Control group (group 3) comprised retrospective patients who received conventional treatment for COVID-19 in hospital.

Results:
Administration of intermittent high-dose iNO therapy combined with continuous low-dose NO supplementation significantly improved physiological interactions in the heart-lung blood circulation system and was not associated with the extrapulmonary organ dysfunction. Safety parameters are presented in Table 1.

Conclusions:
High-dose intermittent iNO therapy combined with continuous low-dose NO gas supplementation may be considered a safe adjuvant modality of treatment for COVID-19 in spontaneously breathing hypoxemic patients.
Abstract 12334: Concerns About the Use of Digoxin in Acute Coronary Syndromes
Authors: Cenko Edina , Bergami Maria , Yoon Jinsung , van der Schaar Mihaela , Kedev Sasko , Gale Chris P , Vasiljevic Zorana , Milicic Davor , Zdravkovic Marija , Krljanac Gordana , Badimon Lina , Manfrini Olivia , Bugiardini Raffaele
Published: April 2024

Introduction:
The use of digitalis has been plagued by controversy since its initial use. Previous observations have shown that digoxin can be safely used in patients with chronic heart failure (HF), but concern remains about the effects of digoxin on mortality in patients with incident HF in the acute setting, especially in those with myocardial infarction.

Hypothesis:
We aimed to determine the relationship between digoxin use and outcomes in hospitalized patients with acute coronary syndromes (ACS) complicated by HF accounting for sex difference and prior heart diseases.

Methods:
We analyzed information on 88,774 patients presenting with acute HF (Killip class ≥2) in the International Survey of Acute Coronary Syndromes (ISACS)-Archives (NCT04008173) registry, 4,722 (18.7%) who received digoxin on hospital admission. Patients with pre-existing nonischemic congestive cardiomyopathy and without HF were excluded, leaving a final study population of 25,187 patients. The main outcome measure was all-cause 30-day mortality. Estimates were evaluated by inverse probability of treatment weighting models.

Results:
Women who received digoxin had a higher rate of death than women who did not receive it (33.8% vs. 29.2 %; relative risk [RR] ratio:1.24;95 % confidence interval [CI]: 1.12-1.37). Similar odds for mortality with digoxin were observed in men (28.5 % vs. 24.9 %; RR ratio 1.20; 95% CI:1.10-1.32). Comparable results were obtained in patients with no prior coronary heart disease (RR ratios:1.26; 95 % CI: 1.10 to 1.45 in women and RR:1.21; 95 % CI: 1.06 to 1.39 in men) and those in sinus rhythm at admission (RR ratios:1.34; 95% CI 1.15 to 1.54 in women and 1.26; 95% CI 1.10 to 1.45 in men).

Conclusions:
Digoxin therapy is associated with an increased risk of early death among women and men with ACS complicated by HF. This finding highlights the need for re-examination of digoxin use in the clinical setting of ACS.
Abstract 12340: Early Restoration of Coronary Vasomotor Function Following Drug-Coated Balloon Only Angioplasty of de novo Lesions
Authors: Kim Sunwon , Lee Jong-Seok , Lim Sang-Yup , Song Woo-Hyuk , Ahn Jeong-Cheon
Published: April 2024

Introduction:
We evaluated whether drug-coated balloon (DCB)-treated
de novo
lesions are prone to vasospasm and how these segments respond to ergonovine and nitrate in comparison with angiographically normal segments and other untreated segments showing prominent vasoreactivity.

Hypothesis:
DCB angioplasty is an emerging treatment approach for coronary artery disease. Evidences in balloon angioplasty era, however, repeatedly reported the presence of abnormal vasomotor function at balloon-injured segment, leading to fatal spasm.

Methods:
68 DCB angioplasty recipients underwent 6-months follow-up coronary angiography. Vasomotor function was assessed using intracoronary injection of incremental dose of ergonovine, followed by nitrate. Percent change of mean lumen diameter was assessed by quantitative coronary angiography at three different sites: DCB-treated segment vs. angiographically normal segment (
control
) vs. normal or mildly diseased segment (diameter stenosis < 30%) showing prominent vasomotor response (
other diseased segment
).

Results:
All patients were event-free during 6-month follow-up. A total of 87 DCB-treated lesions were analyzed. Significant ergonovine-induced vasospasm developed in 8 patients; however, none of them showed focal spasm involving DCB-treated lesion only. There was no significant difference in mean lumen diameter after ergonovine provocation between DCB-treated lesions vs. angiographically normal segments. However, vasoconstrictor response was greater in
other diseased segments
than in DCB-treated lesions. After nitrate injection, all segments dilated significantly. Vasoreactivity, defined as combined constrictor and dilator response, was comparable between DCB-treated lesions and
controls
(p>0.05); while significant difference was found against
other diseased segment
(p<0.005), implicating the restoration of vasomotor function after DCB angioplasty.

Conclusions:
Lesion treated by DCB did not harbor increased risk for clinically or angiographically significant vasospasm and showed vasomotor function similar to angiographically normal segments. These findings support feasibility and safety of DCB-only strategy for the treatment of
de novo
coronary artery disease.
Abstract 12347: Investigating Correlates of Hypertension Among Primarily Hispanic Women
Authors: Lorenzo Elizabeth , Lee Rebecca E. E
Published: April 2024

Introduction:
Under-recognized risk factors (social, economic, cultural, psychological) may contribute to the development of HTN among Hispanic women that warrant investigation. The purpose of this study was to explore the unique contribution of education, food insecurity, household size, Hispanic ethnicity, marital status, neighborhood crime, BMI, waist circumference (WC), and subjective physical activity on HTN, SBP, and DBP on a sample of primarily Hispanic women.

Methods:
Female guardians (
N
= 227, 69.6% Hispanic, 32.7±8.3 years) of preschoolers completed sociodemographic and health history and behavior questionnaires. BMI, WC, SBP, and DBP were objectively measured per protocol. Participants with SBP ≥130 and/or DBP ≥80, on medication for HTN, or diagnosed with HTN were categorized with HTN. Unadjusted bivariate associations, and multivariate linear regression and logistic regression, adjusted for age, were conducted.

Results:
A total of 33.2% of women had HTN and 38.9% were food insecure. Mean BMI was 31.2±7.3 kg/m
2
, WC 99.2±17.2 in., SBP 112.1±12.7 mmHg, and DBP 75.0±10.6 mmHg. HTN was significantly associated with food insecurity (χ
2
(1,
n
= 180) = 4.50,
p
= .046). Women with HTN had significantly higher BMI (32.8±6.9 vs 30.4±7.5,
t
(226) = -2.30,
p
= .023) and WC (103.0±15.3 vs 97.2±17.8,
t
(228) = -2.41,
p
= .017) than those without. In adjusted linear regression models, food insecure women had significantly lower SBP (
B
=-4.44,
p
=.028). Single women had higher SBP (
B
=4.20,
p
=.087), but it did not reach significance, and significantly higher DBP (
B
=4.90,
p
=.022) than married women. As WC increased, SBP increased (
B
=.228,
p
=.077), which trended towards significance, and DBP significantly increased (
B
=.229,
p
=.04). In adjusted logistic regression model, women with food insecurity were less likely to have HTN (OR = .35,
p
=.021) and single women were more likely [OR = 4.19,
p
=.008] to have HTN than married women. There were no other significant associations (
p
s>.05).

Conclusion:
This sample of primarily Hispanic women with food insecurity had lower risks for HTN, an unexpected finding. Single women had a higher risk for HTN than married women suggesting the need for further exploration surrounding psychosocial impacts of marital status on HTN.
Abstract 12359: Measuring Continuous Changes in Individual Cardiovascular Risk for People With Diabetes and Pre-Diabetes
Authors: Sears Lindsay , Guerra Jorge , Patel Veena , Sears Lindsay , Goldner Dan , Dachis Jeff
Published: April 2024

Objective:
For people attempting to lower cardiovascular disease (CV) risk through self-care, feedback on progress can be a strong motivator. Many CV risk scores, however, are based on binary inputs (e.g., whether the subject is diagnosed with diabetes or hypertension). In such cases, incremental improvements in health metrics (e.g., blood glucose, BG; blood pressure, BP), though known to reduce CV risk, will not necessarily reduce the risk score. We modified a well-known risk score to accept continuous inputs and used the modified score to estimate CV risk variability over time for a large sample of people with diabetes.

Method:
One Drop has collected over 25 billion data points from members in all 195 countries, including BP, BG, weight, medication, food, physical activity, heart rate, sleep, comorbidities and demographics. The INTERHEART risk score (IRS) uses CV risk factor information to compute a score ranging from 0 to 40, each point representing a 12% increase in risk. We transformed the risk ratios from published studies of CV risk factors (i.e., BG, BP, BMI, BP medications) to align with the IRS scale, interpolating among reported values by fitting functions via constrained optimization. We applied the modified risk assessment retrospectively to data collected between 2016-2021.

Results:
Among the 2,150 One Drop members included, the majority did not report gender (43%; 32% male) and had type 1 diabetes (78%; 14% type 2; 1% prediabetes; 7% other) with BMI of 28.8±6.9. CV risk scores varied from 2 to 23 IRS points, with six-month standard deviations ranging from 0.008 to 6.379 IRS points. Variations over time for individuals were driven by changes in BG (r = 0.89) more than BP (r = 0.70).

Conclusion:
Established CV risk scores can be modified to replace binary inputs with continuous inputs. This provides a more granular measure of risk to enable more specific intervention personalization and detect smaller changes in risk over time when evaluating interventions. Moreover, people working to lower their CV risk could benefit from seeing that even small changes in their BG, BP, weight and use of medications lead to a reduction of CV risk.
Abstract 12365: Association Between Liver Fibrosis and Left Atrial Remodeling in Patients With Atrial Fibrillation: The Hokuriku-Plus AF Registry
Authors: Tanaka Yoshihiro , Hayashi Kenshi , Tsuda Toyonobu , Kato Takeshi , Fujino Noboru , Sakata Kenji , Usui Soichiro , Kusayama Takashi , Usuda Keisuke , Kawashiri Masa-aki , Yamagishi Masakazu , Takamura Masayuki
Published: April 2024

Introduction:
Fibrosis-4 score (FIB-4), a laboratory-based marker for liver fibrosis, is reportedly associated with increased risks for cardiovascular events and mortality in patients with atrial fibrillation (AF). However, it remains unclear whether FIB-4 is associated with cardiac remodeling in patients with AF.

Hypothesis:
We hypothesized that liver fibrosis might be associated with cardiac remodeling, such as left atrial dilatation and/or systolic dysfunction.

Methods:
The Hokuriku AF Registry is a multicenter, population-based, prospective cohort study including 1,492 AF patients aged 30-94 years from 19 affiliated hospitals. We excluded patients with valvular AF and missing variables at baseline. We conducted a cross-sectional analysis to assess the association between the severity of liver fibrosis based on the FIB-4 score and echocardiographic parameters. The severity of liver fibrosis was classified into three categories based on FIB-4 score (Mild, Intermediate, and Severe) (Table). Unadjusted and adjusted linear regression analysis was performed to compute beta coefficient with 95% confidence interval using the Mild liver fibrosis group as a referent.

Results:
A total of 1,139 non-valvular AF patients were analyzed after the exclusion (mean age 72 ± 10 years, male 73.0%, paroxysmal AF 38.4%). In unadjusted analysis, severe liver fibrosis was significantly associated with increased left atrial diameter (LAD) and decreased left ventricular ejection fraction (LVEF), but this association was not observed in intermediate liver fibrosis. In addition, severe liver fibrosis was independently associated with LAD, not LVEF, after adjusting for other covariates (Table).

Conclusions:
The present study demonstrated that severe liver fibrosis based on FIB-4 score was significantly associated with larger LAD, a surrogate marker for left atrial remodeling, in patients with AF.
Abstract 12395: Nitroglycerin Reduces Pulsatile Arterial Load But Not Steady State Load In Aortic Stenosis Patients Before Or After Transcatheter Aortic Valve Implantation
Authors: Song Ning , Adji Audrey , Hungerford Sara , Namasivayam Mayooran , Hayward Christopher S , Jabbour Andrew , Muller David
Published: April 2024

Background:
Pulsatile arterial load is represented by the characteristic impedance (Zc) of the ascending aorta. In aortic stenosis (AS) patients, Zc is thought to contribute significantly to left ventricular afterload in addition to aortic transvalvular gradient. We evaluated the effect of nitroglycerin, a potent vasodilator, on Zc non-invasively in AS patients before or after transcatheter aortic valve implantation (TAVI).

Methods:
Simultaneous aortic pressure from radial arterial tonometry and flow from cardiac magnetic resonance phase contrast imaging were obtained. Radial waveforms were converted to central aortic pressure using SphygmoCor 8.1 (AtCor Medical) and calibrated using brachial cuff values. Zc was derived from aortic pressure and flow by averaging the impedance modulus in frequency domain analysis. Data acquisition was repeated after administration of 300 micrograms of sublingual nitroglycerin to investigate its effect on pulsatile and steady state load.

Results:
Analysis was performed in 9 AS patients (3 female, age 68-81 years) with a left ventricular ejection fraction
>
55%, of whom 5 had undergone recent TAVI. When compared with baseline measurements, nitroglycerin reduced mean arterial pressure (107 ± 11 pre vs 87 ± 5 post, mmHg), central pulse pressure (67 ± 15 pre vs 48 ± 13 post, mmHg), forward stroke volume (83 ± 15 pre vs 70 ± 13 post, ml) and Zc (129 ± 42 pre vs 95 ± 32 post, dynes.cm/s
5
). However, there was no change in compliance or steady state systemic vascular resistance (2163 ± 445 pre vs 2045 ± 485 post, dynes.cm/s
5
).

Conclusion:
Nitroglycerin significantly reduces pulsatile arterial load in AS patients without reducing steady state load. Our non-invasive technique can reliably assess changes in hemodynamic loading conditions, and larger longitudinal paired analysis of nitroglycerin response before and after TAVI may help predict AS patients at risk of poorer outcomes from ventriculo-arterial coupling mismatch following treatment.
Abstract 12405: Treatment With Impella and Veno-Arterial Extracorporeal Membrane Oxygenation During Extracorporeal Cardiopulmonary Resuscitation Improves Survival - A Multicenter Cohort Study
Authors: Thevathasan Tharusan , Kenny Megan , Boie Sebastian , Wurster Thomas , Last Jana , Kalinowsky Rene , Landmesser Ulf , Balzer Felix , Skurk Carsten
Published: April 2024

Introduction:
Left ventricular (LV) unloading with Impella has been shown to improve survival in patients with cardiogenic shock treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). This study aimed to investigate whether treatment with VA-ECMO and Impella (so called “ECMELLA”) during extracorporeal cardiopulmonary resuscitation (i.e., cardiac arrest due to myocardial infarction and no return of spontaneous circulation at device implantation) was associated with improved outcomes.

Hypothesis:
ECMELLA treatment is associated with improved survival (primary outcome) as well as prolonged hospital and ICU length of stay (secondary outcomes) compared to VA-ECMO treatment.

Methods:
Cox proportional-hazard and Poisson regression models were used to analyze the association between treatment groups (ECMELLA vs. VA-ECMO) and outcomes. Analyses were adjusted for age, sex, body mass index, type of ECG rhythm (shockable vs. non-shockable), location of cardiac arrest (out of hospital vs. in-hospital) as well as first lactate and pH levels after device implantation.

Results:
93 adult patients from three tertiary care centers were included, out of whom 52 (56%) received ECMELLA and 41 (44%) received VA-ECMO treatment. ECMELLA treatment was associated with decreased in-hospital mortality (HR 0.41 [95% CI 0.22-0.79], P=0.007), prolonged hospital (IRR 1.70 [95% CI 1.46-1.98], P<0.001) and ICU length of stay (IRR 1.67 [95% CI 1.42-1.96], P<0.001). Kaplan-Meier analysis confirmed survival benefits in the ECMELLA group (P=0.004, Figure 1). With an exploratory intent, we showed that LV ejection fraction was severely impaired at ICU admission immediately after device implantation (19% ECMELLA vs. 21% ECMO) but improved strongly in ECMELLA group at ICU discharge (38% ECMELLA vs. 31% ECMO).

Conclusion:
LV unloading in patients treated with VA-ECMO was associated with lower mortality rates during extracorporeal cardiopulmonary resuscitation.
Abstract 12414: 3D Fusion of MRI Mechanical Activation, Cardioinsight Electrical Activation, and Fluoroscopic Lead Location for CRT
Authors: Bilchick Kenneth C , Oomen Pim , Abdi Mohamad , Setser Randoph , Epstein Frederick , Holmes Jeffrey
Published: April 2024

Introduction:
3D image integration can help achieve personalized medicine for patients undergoing device therapy for heart failure, such as cardiac resynchronization therapy (CRT).

Hypothesis:
Electrical mapping data and mechanical activation from cardiac magnetic resonance (CMR) integrated with live fluoroscopic data will provide complementary information to optimize CRT procedures.

Methods:
Ten patients underwent cardiac CT and electrical mapping with the CardioInsight 252-electrode vest (Medtronic) during CRT implantation using a 3D-capable fluoroscopy system (Artis zeego, Siemens) and a 3D image integration software prototype (Guide-CRT, Siemens). A myocardial mechanical activation map based on strain from CMR Displacement Encoding with Stimulated Echoes (DENSE) and an electrical activation map from CardioInsight were fused with fluoroscopic images using Guide-CRT.

Results:
In a representative patient with LBBB and QRS duration 140 ms, integrated 3D maps of electrical and mechanical activation with the fluoroscopic lead location are shown for right/left anterior oblique (RAO/LAO) and anterior-posterior (AP) views (Figure). While the area of late mechanical activation is centered at about 3 o’clock on the mitral annulus, a slightly more anterolateral and smaller focus of late electrical activation is noted on the CardioInsight maps (Figure). Furthermore, more basal activation data is possible with the electrical maps, as strain imaging typically starts below the mitral valve. While a middle LV electrode (LV2-4) was chosen for CRT pacing based on the CMR map, the more proximal and anterolateral LV electrode could have been chosen based on the electrical map.

Conclusions:
Multimodality mapping and 3D fusion of mechanical activation, electrical activation, and lead position provide important information regarding electromechanical coupling and the choice of the optimal pacing location.
Abstract 12429: What is the Clinical Impact of Echocardiography Among Hospitalized Patients With Prior Testing?
Authors: Pervaiz Abdullah , Kadado Anis John , Gobeil Kyle , Walia Ritika , Elder Petal , Battisha Ayman , Shikari Saima , Lagu Tara , Hiser William L , Pack Quinn
Published: April 2024

Introduction:
The versatility and safety of transthoracic echocardiography (TTE) has made it one of the most frequently ordered cardiac imaging tests. However, for inpatients with prior TTE results, the clinical impact of repeat TTE remains uncertain.

Methods:
We evaluated the charts of sequential hospitalized patients with prior TTE results who underwent an inpatient TTE. We noted prior and current TTE results, if imaging findings were abnormal [(using definitions from Hua (Echocardiography, 2017)], and if these findings were significantly different between the studies. We then evaluated all records for changes in clinical management, including medication changes, additional diagnostic testing, new specialty consultation, or invasive procedures. We used a multivariable model to determine predictors of changes in clinical management.

Results:
Of 229 sequential patients who underwent an inpatient TTE [median age 71, 55% male, 90% white, 67% abnormal prior TTE], most met Appropriate Use Criteria (92%), most were abnormal (80%), and most changed in at least one aspect from the prior study (66%). However, despite the majority of repeat TTEs with new changes, clinical management was impacted in only a minority of cases 61 (27%). Of these, 27 (12%) resulted in medication changes; 15 (6%) had further diagnostic testing; 14 (6%) had a new specialty consultation; and 11 (4%) had invasive procedures ordered (cardiac catheterization, pericardial drain placement, and cardiac surgery). After adjusting for ordering provider, race of patient, and study indication, new findings on the TTE predicted changes in clinical management OR 4.2, p<0.001).

Conclusion:
Despite the large majority of repeat TTE’s meeting AUC guidelines, being abnormal, and having imaging changes, repeat TTE infrequently impacted clinical management. Although new TTE abnormalities are associated with clinical management changes in some cases, the clinical value of repeat TTE in the setting of prior imaging results may be lower than most clinicians assume. Efforts to identify the population for whom TTE studies are most likely to impact clinical care would increase the clinical yield of repeat TTE.
Abstract 12443: Predictors of Long-Term Adherence to Exercise in Adults With Heart Failure Enrolled in an Exercise Clinical Trial
Authors: Alonso Windy W , Kupzyk Kevin , Norman Joseph F , Lundgren Scott , Faulkner Kenneth , KETEYIAN Steven J , Bills Sara , Pozehl Bunny J
Published: April 2024

Introduction:
Exercise is recommended for adults with heart failure (HF), but long-term adherence to exercise is poor. The purpose of this analysis is to determine predictors of long-term adherence to exercise in adults with HF enrolled in a RCT testing effects of a behavioral intervention compared to enhanced usual care (EUC) on long-term adherence to exercise.

Hypothesis:
Unmodifiable (e.g. gender, race, age) and modifiable (e.g. physical function, self-regulation, attitudes) variables predict long-term adherence to exercise in adults with HF.

Methods:
All subjects (n=204) in this 2-group RCT received paid access to a fitness center for 18 months. Subjects in the intervention group (n=102) also received weekly coaching for 12 months. Adherence was defined as 120 minutes of moderate-intensity exercise weekly. Logistic regression models to examine predictors by group included baseline variables that significantly related to adherence at 12 or 18 months: gender, BMI, 6-minute walk test distance, attitudes, self-regulation, and health status.

Results:
The sample was 55% men, 47% non-white, and 71% HF with reduced ejection fraction. Mean age was 60.4 years. In the intervention group, gender predicted adherence at both 12 (B=-1.36, p=.01) and 18 months (B=-2.48, p=.003) with men achieving greater adherence at both time points. In the EUC group, no variables in the final model predicted adherence at 12 months and at 18 months, adherence was predicted by baseline scores on the Physical Activity Self-Regulation Scale (B=.084, p=.007) with higher self-regulation associated with a greater likelihood of adherence.

Conclusions:
To our knowledge, this is the first study to report predictors of long-term adherence to exercise in adults with HF. Men with HF achieved greater adherence to exercise than women following a behavioral coaching intervention. Future studies are necessary to identify behavioral strategies that will promote long-term adherence to exercise in women with HF. Adults with HF that can self-regulate at baseline adhere better to long-term exercise if given guidance to exercise and paid access to a fitness center. These findings are important as we move toward a precision health approach to improve long-term exercise adherence in adults with HF.
Abstract 12453: Smooth Muscle-Specific Latexin Deficiency Prevents Platelet-Derived Growth Factor-Mediated Vascular Smooth Muscle Cell Phenotypic Switch and Neointimal Formation
Authors: Kazama Kyosuke , Liu Wennan , Zhang Chen , Sun Xiaobo , Sun Jianxin
Published: April 2024

Introduction:
Vascular smooth muscle cell (SMC) phenotypic switch from a contractile to a synthetic phenotype plays a significant role in vascular pathologies, including atherosclerosis, restenosis, and aneurysm. Latexin (LXN) is a novel inflammatory protein that is highly expressed in SMCs; the role of LXN in SMCs biology, however, remains largely unknown.

Methods:
Both global and SMC-specific LXN-knockout mice were generated to determine the
in vivo
function of LXN in SMC remolding. Neointimal formation induced by mouse carotid artery ligation was assessed by HE staining. Mouse SMCs were isolated from thoracic aortas and used for biological and functional assays. Western blot (WB), immunohistochemistry (IHC), RNA-seq, and quantitative polymerase chain reaction (qPCR) were used to assess protein and gene expression. BrdU incorporation assay and Boyden’s chamber assay were used to assess SMC proliferation and migration.

Results:
The expression of contractile SMC markers were down-regulated, while synthetic SMC markers were up-regulated in the mouse model of carotid artery ligation. LXN expression was significantly increased in mouse carotid arteries after ligation-induced injury. Furthermore, we found that both global and SMC-specific deletion of LXN significantly attenuated neointimal formation after injury, implicating an essential role of LXN in the modulation of SMC phenotype. Our
ex vivo
and
in vitro
functional assays showed that LXN deficiency attenuates SMC proliferation and migration, which is consistent with our RNA-seq data showing that the expression of cell proliferation-related genes was down-regulated in LXN deficient mouse SMCs. Mechanistically, we identified platelet-derived growth factor receptor alpha as a critical mediator involved in regulating SMC phenotypic switch by LXN.

Conclusions:
Our results for the first time identify LXN as a critical mediator in regulating SMC phenotypic switch and suggest that inhibition of LXN may represent a novel therapeutic strategy for the treatment of proliferative vascular diseases such as atherosclerosis and restenosis.
Abstract 12459: Downregulated Fli1 in Scleroderma Myeloid Cells May Contribute to Cardiac Fibrosis via a Galectin-3/mTOR Dependent Pathway
Authors: el adili fatima , Najem Mortada , Trojanowska Maria , Bujor Andreea M
Published: April 2024

Introduction:
Scleroderma (SSc) is an autoimmune fibrotic disease with high mortality and no effective therapies. Cardiac fibrosis in SSc is common and has a poor prognosis, but pathogenesis is unclear. Galectin-3 secretion by macrophages has been implicated in cardiac fibrosis, but its specific contribution to SSc cardiac disease has not been elucidated. We recently demonstrated that Fli1, a member of the Ets family of transcription factors, is decreased in SSc myeloid cells, and that Fli1 depleted macrophages have a profibrotic phenotype. We aim to evaluate the contribution of myeloid Fli1 to SSc cardiac fibrosis.

Methods:
Levels of galectin-3 were assessed by ELISA in serum, and qPCR and immunofluorescence in monocytes. Primary human cardiac fibroblasts were co-cultured with macrophages using inserts. Rapamycin (10nM) was used to treat the co-cultures. Western blot was used to assess protein levels of collagen and p70S6K. Collagen deposition in hearts from mice with conditional deletion of Fli1 in macrophages (

LysMCre/Fli1
fl/f

l
) was assessed by picrosirius red.

Results:
SSc patients had higher expression of galectin-3 in monocytes and serum compared to healthy controls. Co-culture of human cardiac fibroblasts and Fli1 depleted macrophages resulted in induction of galectin-3 expression by macrophages, and activation of the mTOR/p70S6K pathway with enhanced collagen type I protein deposition by fibroblasts. These effects were blocked by the mTOR inhibitor Rapamycin, and by treatment of macrophages with siRNA against galectin-3. Deletion of Fli1 in macrophages via Cre-mediated recombination using
LysMCre
mice predisposed mice to develop cardiac fibrosis.

Conclusions:
These findings suggest that Fli1 deficiency in macrophages may contribute to SSc cardiac fibrosis, and that Rapamycin may be a potential therapeutic option for heart involvement in SSc.
Abstract 12482: Exposure to Greenspace Reduces Blood Pressure and Attenuates the Association With Air Pollution in Tamil Nadu, India
Authors: Lane Kevin J , Black-Ingersoll Flannery , thanikachalam sadagopan , Thanikachalam Mohan
Published: April 2024

Background:
Globally, high systolic blood pressure (SBP) is a major cause for cardiovascular mortality. Air pollution affects SBP and diastolic blood pressure (DBP), but has not been studied in relation to greenness in rapidly urbanizing and polluted areas. Here we assess the association between long-term concentrations of ambient PM
2.5,
greenness and blood pressure in the Population study of Urban, Rural, Semi-urban Endovascular disease and Holistic Intervention Study (PURSE-HIS) in Tamil Nadu, India.

Methods:
The study included 8080 randomly selected participants (mean age 42 years; 58% women). We measured greenness using MODIS satellite derived normalized difference vegetation index (NDVI) at 250 m
2
resolutions. We used modeled estimates of annual average PM
2.5
at 1 km
2
developed for Global Burden of Disease to assign to residences. Brachial SBP and DBP were assessed in the dominant arm and an average of three measurements was used in the analysis. The associations were examined using generalized linear regression models controlling for age, gender, waist circumference, physical activity, sodium intake, smoking, stress, and anxiety.

Results:
The PM
2.5
exposure estimates ranged from 18μg/m
3
to 35μg/m
3
in the study area. In independent multivariate models IQR increase in PM
2.5
(3.0 μg/m
3
) was associated with a 5.5 mmHg (95%CI: 4.9, 6.2) change in SBP. Stratification of participants into greenness exposures of high, medium and low, showed markedly higher association of PM
2.5
with SBP when comparing those residing in low greenness areas (5.0 mmHg [95%CI: 3, 6.9]) to those in medium (3.7 mmHg [95%CI: 2.8, 4.6]) and high NDVI areas (1.1 mmHg [95%CI: -0.6, 2.8]).

Conclusions:
Greenness and PM
2.5
were associated with SBP and DBP independently, with significant modification of this association by greenness. Further studies are required to assess interaction between PM
2.5
and greenness on SBP.
Abstract 12491: Use of a Self-Care Mobile Phone Application Can Improve Patient Education and Medication Adherence in Patients With Acute Decompensated Heart Failure
Authors: essa Hani , kevin mohee , balu ashwin , brousas sophia , Whybrow-huppatz Isobel , kochhar sanjana , jackson carolyn , murphy naomi , kelly annmarie , douglas homeyra , sankaranarayanan rajiv
Published: April 2024

Introduction:
The use of digital health technologies using mobile phone health applications has increased over the last few years. We developed a mobile phone application (APP) (Aintree Heart Failure Passport APP) for heart failure (HF) patient self-education and improved medication adherence. The APP consisted of a Traffic Light System for education self-care advice, prompt for medications, reminder of appointments, educational videos as well as a mood check questionnaire.

Methods:
This was a pilot feasibility study in a British university hospital conducted in 2019 and 2020. We assessed self-care behaviour following the use of the Aintree Heart Failure Passport Mobile APP in a cohort of patients with acute decompensated HF. We employed the use of European Heart Failure Self-care Behaviour scale (EHFSBs), medication adherence using the Medication Adherence Report Scale (MARS-5) at 2 weeks and compared 30-day HF readmissions with annual hospital HF data. Descriptive statistics were represented as continuous variables as means with standard deviations. Categorical variables were represented with percentages and analysed using Chi-squared test.

Results:
102 patients with acute decompensated HF were recruited to this pilot feasibility study. 57% were men and mean age 56 years±5.1. 55% patients had HF with reduced ejection fraction (HFrEF), 34% had HF with preserved EF (HFpEF) and 11% had HF with mid-range EF. Mean EHFSBs was 19.7±6.1and mean MARS-5 score was 23.5±1. 10/102 (10%) patients were re-hospitalised with HF compared to the annual hospital HF rehospitalisation incidence which was 19% (95/393); p=0.04.

Conclusions:
Results from our pilot feasibility study suggest that use of a HF self care mobile phone APP (Aintree Heart Failure Passport App) in patients with acute decompensated HF, leads to high quality self care behaviour, high levels of medication adherence and lower levels of 30-day HF re-hospitalisation. These results will need to be validated in a randomised controlled trial.
Abstract 12522: Semaphorin-3F Suppresses Vascular Permeability and Inflammation
Authors: Gao Yao , Li David , Balasubbramanian Dakshnapriya , Almazyad Asma , Chen Hong , Briscoe David , Adam Rosalyn , Bielenberg Diane
Published: April 2024

The endothelium mediates microvascular fluid exchange between the blood and the interstitial tissue compartments. Vascular endothelial growth factor (VEGF-A) mediates vascular permeability via its tyrosine kinase receptor VEGFR2. However, the role of Neuropilin-2 (Nrp2), a co-receptor for both VEGF-A and Semaphorin-3F (SEMA3F), in vascular leakage is less understood.
Nrp2
-deficient mice show enhanced and prolonged swelling in acute inflammation models. We hypothesize that endogenous Sema3F acts as a competitive ligand with VEGF-A for Nrp2 and that Sema3F/Nrp2 signaling reduces edema by inhibiting vascular permeability and promoting a quickened resolution of inflammation. To test our hypothesis we compared tissue thickness and vascular permeability in constitutive or tissue-specific, inducible
Sema3F
-deficient mice and control littermates under basal conditions or following cutaneous, acute delayed-type hypersensitivity reactions in the ear. Our results demonstrate that depletion of SEMA3F protein, either genetically using knockout mice or pharmacologically using systemic administration of SEMA3F neutralizing antibodies, significantly prolonged tissue swelling and increased vascular permeability compared to control mice during acute inflammation. Conversely, intravenous injection of SEMA3F adenovirus decreased ear swelling and edema during acute inflammation compared to control virus. Using proximity ligation assays, VEGFA/Nrp2 binding was found to be dramatically increased in
Sema3F
-knockout mice compared to wildtype mice. Taken together, our results demonstrate that the NRP2 signaling cascade mediates fluid homeostasis via its stimulatory (VEGFA) and inhibitory (SEMA3F) ligands during inflammatory reactions. SEMA3F acts as a competitive ligand with VEGFA binding to Nrp2 and promotes resolution by attenuating vascular permeability leading to reduced inflammation and edema. Our research suggests that the NRP2 axis may be a potential therapeutic target for inflammation-mediated diseases.
Abstract 12530: Impact of Multiple Lifestyle Intervention on Body Weight, Insulin Sensitivity and Remission of Type 2 Diabetes: A Single-Center Experience
Authors: Iglesies-Grau Josep , Dionne Valérie , Pelletier Véronique , Bisaillon Marc , Bherer Louis , Bouabdallaoui Nadia , Nigam Anil , Juneau Martin , L'Allier Philippe L
Published: April 2024

Introduction:
Type 2 diabetes (T2D) and pre-diabetes are mostly lifestyle diseases associated with high rates of morbidity, mortality, and health care expenditures.

Hypothesis:
The Montreal Heart Institute Cardiovascular Prevention EPIC Center started a comprehensive lifestyle clinic for patients with T2D in 2019. We sought to study the impacts of a 12-month non-pharmacological intervention on body weight, insulin sensitivity and remission of T2D.

Methods:
Between January and December 2019, 105 with T2D (HbA1c ≥ 6.5%) were recruited. Anthropometric measures and fasting blood analysis were measured at 0,3,6 and 12 months. All patients received regular nutritional counselling and personalized physical exercise prescription. Glucose-lowering therapies were not modified, unless necessary. Partial and complete remission of diabetes were defined by HbA1c <6.5% and HbA1c <5.7% respectively, for at least 3 months. Differences in means across variables with repeated observations were assessed with ANOVA. Factors associated with obtaining partial remission at 3 months were analyzed using a multivariate logistic model.

Results:
96 patients completed the intervention (91%), mean age was 67.5±10.5 years, 72% male, 37% with coronary heart disease, 23% without glucose-lowering therapies. Mean baseline HbA1c was 7.3±0.8 %. At program end, all anthropometric and insulin resistance measures were significantly improved (Table 1); HbA1c -0.78 (95CI: -0.57 à -0.98, p<0.001). Gains were achieved at 3 months and were maintained during the program without significant change. Partial remission was achieved in 56.1% (95CI: 45.1 to 66.5%) and complete remission of diabetes was attained in 11% (95CI: 5.7 to 19.9%) of participants. Adjusted by age, sex, treatment, baselineHbA1c and weight loss at 3 months; individuals with low HbA1c (p=0.01) and those that lost >3.5Kg at 3 months (OR 4.1, 95%CI: 1.5 to 11.1, p=0.005) were significantly more likely to attain partial remission.

Conclusions:
Prioritizing lifestyle changes were shown to improve anthropometric and insulin resistance measures even to the point of normalizing some metabolic values among subjects with T2D. These changes were mostly achieved after 3 months and were maintained throughout the intervention.