bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4144388: Impact of Left Atrial Myopathy and Post-Ablation Remodeling on Quality of Life: A DECAAF II Subanalysis
Authors: bidaoui ghassan , Feng Han , Chouman Nour , Assaf Ala' , Younes Hadi , Bsoul Mayana , Tirado Polo Francisco , Lim Chanho , Jia Yishi , Liu Yingshuo , Rittmeyer William , Mekhael Mario , Noujaim Charbel , Pandey Amitabh , Rao Swati , Kreidieh Omar , Marrouche Nassir , donnellan eoin
Published: November 2024

Background:
Atrial fibrillation (AF) is associated with adverse remodeling of the left atrium (LA). The impact of the extent of atrial myopathy and post-ablation remodeling on quality-of-life (QoL) outcomes have not been studied.

Objective:
The aim of our study was to investigate the association between atrial myopathy and post-ablation remodeling on quality-of-life outcomes in patients with persistent AF.

Methods:
We conducted an analysis of DECAAF II participants who underwent late-gadolinium enhancement MRI (LGE-MRI) before and after AF ablation. We assessed atrial myopathy and post-ablation atrial remodeling, scar formation, and fibrosis coverage with ablation. QoL metrics were assessed using the Short Form Survey (SF-36) and Atrial Fibrillation Severity Scale (AFSS). Uni- and multivariable regression models were developed for this analysis.

Results:
613 patients with persistent AF were included in our analyses. At baseline, AFSS burden and total AFSS score were 18.94±7.35 and 12.24±8.17, respectively. Following ablation, all QoL and AFSS metrics improved in both the pulmonary vein isolation (PVI) and MRI-guided fibrosis ablation groups. On average, one unit of post-ablation reduction in left atrial volume index (LAVI) was associated with an improvement of 0.085 in total AFSS score (p=0.001), 0.01 in shortness of breath with activity (p<0.001), 0.15 in AF burden (p<0.001), -0.016 in global well-being (p=0.018), 0.519 in health change (p<0.001), 0.19 in vitality (vitality (p=0.01), and 0.27 in physical functioning (p=0.001). Baseline fibrosis and residual fibrosis post-ablation were associated with improved vitality and general health.

Conclusion:
Atrial myopathy and post-ablation atrial remodeling significantly impact QoL in patients with persistent AF undergoing ablation.
Abstract 4144394: Cardiac Resynchronization Therapy is Associated with Increased All-Cause Mortality in Patients with Chronic Chagas Cardiomyopathy: Systematic Review and Meta-analysis
Authors: Franco Hondermann Beatriz Maria , franco Hondermann Juan Bosco , Jansen amorim Ana Karla
Published: November 2024

Introduction:
Cardiac resynchronization therapy (CRT) reduces mortality in patients with moderate to severe heart failure (HF) and reduced ejection fraction. However, outcomes associated with CRT in CCC patients are still controversial. We conducted a meta-analysis to quantify total mortality in patients with chronic Chagas cardiomyopathy compared to HF of other etiologies (Non-Chagas).

Objectives:
To perform a meta-analysis of studies to measure all-cause mortality in CCC patients compared to patients of other etiologies (Non-Chagas) when undergoing CRT.

Methods:
A literature search was conducted in PubMed, Cochrane, Embase, Scielo for English, Portuguese, and Spanish comparing all-cause mortality in patients undergoing CRT in CCC and other etiologies (Non-Chagas). The Non-Chagas group included patients with HF of ischemic, dilated, or idiopathic etiology. Statistical analysis was performed in RevMan 5.18. Heterogeneity was assessed by I2 statistics.

Results:
577 patients from 3 studies were included, with 170 patients having Chronic Chagas Cardiomyopathy. Follow-up time ranged from 12 to 41 months. Mean age was 61.7 +/- 11.6 years and 61.5% were male. Mean ejection fraction across studies was 25.8% +/- 6.4.

All-cause mortality (OR: 2.41; 95% CI: 1.65-3.53; p < 0.00001, I2 = 0%) was significantly higher in patients with Chronic Chagas Cardiomyopathy compared to the Non-Chagas group.

Conclusion:
Patients with CCC had higher all-cause mortality compared to Non-Chagas patients when undergoing CRT. These results highlight the importance of prospective controlled studies comparing Cardiac Resynchronization Therapy with other treatments to define the optimal therapy for patients with heart failure with reduced ejection fraction due to Chagas disease.
Abstract 4144399: Impact of Protein-Calorie Malnutrition on Peri-procedural Outcomes of Transcatheter Aortic Valve Replacement: Latest Insights from National Database
Authors: Haider Mobeen , Kurpad Krishna , Khalid Yousra , Vorla Mounica , KATAMREDDY ADARSH , Jahan Sultana , Moussa Issam , adoni naveed , Mehta Sanjay , balla sudarshan
Published: November 2024

Introduction:
Transcatheter aortic valve replacement (TAVR) has emerged as an effective and less invasive percutaneous treatment option for select patients with severe aortic stenosis. Nutritional status plays a role in risk stratification for TAVR given its impact on peri-procedural outcomes. We aim to evaluate the impact of protein-calorie malnutrition (PCM) on the outcomes of TAVR.

Methods:
We queried the national inpatient sample database from year 2016 - 2020 to identify all patients who underwent TAVR. They were classified based on the presence of protein-calorie malnutrition. Statistical significance was assigned at p<05.

Results:
A total of 303310 patients underwent TAVR. 7430 patients among them had a diagnosis of PCM. Baseline demographics and comorbidities are presented in the table below. Patients with malnutrition had a higher prevalence of chronic lung disease, atrial fibrillation, chronic kidney disease, end-stage renal disease, and chronic liver disease were sicker at baseline as demonstrated by higher Charlson comorbidity index (53.51 vs 69.45, p-value: 0.001). With regards to in-hospital outcomes, the PCM group had a higher incidence of total major bleeding, post-operative deep venous thrombosis/pulmonary embolism, total vascular complications, and in-hospital mortality in patients with PCM as compared to those without. With regards to healthcare resource utilization, TAVR patients with PCM had a longer length of hospital stay and higher total charges. The multivariate analysis reveals that PCM is associated with higher in-hospital mortality (OR: 3.97 with 95% CI: 3.11-5.06).

Conclusion:
Protein calorie malnutrition is associated with worse outcomes with higher mortality, morbidity, and increased healthcare resource utilization in patients undergoing TAVR. Nutritional optimization should be considered when feasible in this challenging patient population. Studies are needed to understand the mechanisms for worse outcomes in the PCM group
Abstract 4144409: Visualizing Chronic Myocardial Infarction using Native T1-weighted Signal Intensity Patterns with Similar Image Contrast as LGE MRI
Authors: Youssef Khalid , Zhang Xinheng , Yoosefian Ghazal , Chen Yinyin , Chan Shing Fai , yang hsin-jung , Vora Keyur , Howarth Andrew , Kumar Andreas , Sharif Behzad , Dharmakumar Rohan
Published: November 2024

Background:
The identification of chronic myocardial infarction (MI) typically relies on contrast-enhanced MRI, late-gadolinium enhancement (LGE) MRI. Native (contrast-free) T1 mapping at 3T has been shown to identify chronic MI but visualization of it is more difficult compared to LGE MRI. Data-driven utilization of distinctive native T1-weighted MRI signal intensity patterns in infarcted and remote myocardium may be a superior alternative to standard native-T1 mapping. We hypothesized that native T1-weighted signal intensity patterns can be used to generate images of chronic MI with similar contrast-to-noise ratio (CNR) to LGE MRI. We tested this hypothesis using a data-driven approach applied to native T1-weighted signal patterns of chronic MI and compared the resulting CNR to the CNRs of LGE and native T1 maps at 3T.

Methods:
The study included a dataset of spatially aligned short-axis, native-T1-weighted and LGE images of hearts from canine (n=24) with surgically implemented chronic MI. Unsupervised clustering techniques (self-organizing maps and t-distributed stochastic neighbor embedding) were used to analyze the T1-weighted images to arrive at native T1-weighted pixel intensity patterns. Data-driven native mapping (DNM) utilizing deep neural networks were used to map these patterns to corresponding pixels in LGE images. This allowed for creation of visually enhanced maps with improved chronic MI contrast. Pearson correlation analysis compared DNM with standard T1 maps.

Results:
Native T1-weighted images showed distinct pixel intensity patterns between infarcted and remote myocardium. CNR from DNM (mean ± SD, 15.01±2.88) was significantly higher than native T1 maps (5.64±1.58, p<0.001) but not different from LGE images (15.51±2.43, p=0.40). Infarcted areas in LGE images correlated more strongly with DNM (R
2
=0.85) than with native T1 maps (R
2
=0.71, p<0.001).

Conclusion:
Native T1-weighted pixels contain information that can be extracted using the DNM approach to enhance image contrast between infarcted and remote myocardium. The proposed approach allows for robust visualization of chronic infarct territories without contrast agents, offering a viable contrast-agent-free alternative to LGE MRI. Patient studies are needed for clinical translation.
Abstract 4144426: How does intensive blood pressure control reduce the risk of cardiovascular disease events? A biomarker-based mediation analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)
Authors: Segar Matthew , Khan Safi , Nasir Khurram , Shafi Tariq , Januzzi James , Arora Pankaj , Butler Javed , Patel Kershaw
Published: November 2024

Introduction:
Intensive blood pressure (BP) control is associated with a significant reduction in the risk of heart failure (HF) or all-cause death. However, the extent to which intensive BP control-associated HF risk reduction is mediated by changes in subclinical markers of cardiovascular (CV) disease (CVD) and stage B HF is not well-characterized.

Methods:
Participants of the Systolic Blood Pressure Intervention Trial (SPRINT) with hypertension and available data on subclinical CVD markers at baseline and follow-up (1- or 2-year visit) were included. The key subclinical markers of CVD analyzed included chronic myocardial injury (assessed by high-sensitivity cardiac troponin I [hs-cTnI]), neurohormonal stress (assessed by N-terminal pro-B-type natriuretic peptide [NT-proBNP]), left ventricular (LV) mass (assessed by electrocardiogram Cornell voltage [CV]), and arterial stiffness (assessed by estimated pulse wave velocity [ePWV]). A counterfactual framework was used to assess the effects of the exposure and mediator on key outcomes, including 1) HF / all-cause death; 2) atherosclerotic CVD (ASCVD), including nonfatal myocardial infarction, nonfatal stroke, or CV death.

Results:
The present study included 8,872 participants (35% women, 31% Black). Over the 3.3-year median follow-up, there were 333 (3.8%) HF / all-cause death events and 200 (2.3%) ASCVD events. Reductions in neurohormonal stress and LV mass mediated up to 15% of the reduction in risk of HF / all-cause death with intensive BP control (
Table
). In contrast, treatment-related changes in chronic myocardial injury and arterial stiffness did not mediate the benefits of intensive BP reduction on HF / all-cause death risk. Furthermore, changes in any subclinical CVD markers did not mediate the effect of intensive BP control on ASCVD risk (
Table
).

Conclusions:
In this post-hoc analysis of SPRINT, improvements in neurohormonal stress and LV mass, as identified by surrogate markers of hs-cTnI and CV, were important mediators of the beneficial effects of intensive BP control in reducing the risk of HF / all-cause death. Mediators of the effect of intensive vs. standard BP control for reducing HF / all-cause death differ from those for ASCVD.
Abstract 4144437: Limited Effect of Circulating Sex Hormones on Cardiac and Vascular Physiology with Healthy Aging
Authors: Brazile Tiffany , Wakeham Denis , De Oliveira Gomes Diana , Hearon Christopher , Macnamara James , Levine Benjamin , Sarma Satyam
Published: November 2024

Background:
Sex differences in cardiac and vascular aging, including the disparate risk for heart failure with preserved ejection fraction (HFpEF) in women may be mediated by declines in sex hormones. It is unknown if hormone levels affect subclinical cardiovascular changes with aging that predispose women to HFpEF; therefore, we compared hormone levels and afterload, arterial and left ventricular (LV) stiffness across age in healthy men and women.

Methods:
We studied 194 sedentary normotensive, non-obese adults (55% female; age: 21-88yrs) at rest and maximal exercise. Arterial stiffness was assessed as carotid-femoral pulse wave velocity (PWV). Afterload was assessed at rest with aortic augmentation pressure (aAP), calculated from reconstructed ascending aortic blood pressure (BP) waveforms (SphygmoCor), and at maximal exercise as effective arterial elastance (Ea; systolic BP/stroke volume [derived from C
2
H
2
rebreathe]). Myocardial stiffness was assessed as the slope of individual pressure-volume (right heart catheterization-echocardiography) curves generated by graded LV loading and unloading. Serum Testosterone (T), estradiol, and follicle stimulating hormone (FSH) were measured (TOSOH Bioanalyzer). The effect of age, sex, and hormones were assessed via multivariate linear regression.

Results:
FSH increased exponentially with age with higher levels in women (Figure A, p<0.001). FSH was associated with Ea (p=0.048, β=0.003) with a small effect size, but not aAP (p=0.078, β=0.017). The effect for FSH was eliminated when adding a sex*hormone level term (Figure B). T declined at >3-fold the rate with age in men (Figure A, p<0.001) and was associated with Ea, also with a small effect size (p=0.041, β=0.001, Figure B). There was no association between FSH or T with arterial or myocardial stiffness (all, p>0.565, β<0.002).

Conclusion:
Higher exercise afterload with increasing age in women was associated with progressively higher levels of FSH and lower levels of T. In healthy adults, the effects of circulating sex hormones were small relative to the effects of age and sex, and therefore likely do not explain the elevated HFpEF risk in women.
Abstract 4144448: Evaluation of 3D Bioprinted Pulsatile Conduits Engineered Using Human Stem Cell-Derived Cardiomyocytes in a Murine Model
Authors: Ashraf Syed Faaz , Bliley Jaci , Yi Tai , Leland Joseph , Kang Amanda , Stang Maria , Dikyol Caner , Behre Anne , Tzeng Edith , breuer christopher , Feinberg Adam
Published: November 2024

Introduction:
Patients with single ventricle disease and Fontan circulation suffer long-term morbidity due to the lack of a sub-pulmonary ventricle. The concept of a pulsatile Fontan conduit, functioning as a sub-pulmonary ‘neo-ventricle,’ using engineered heart tissue (EHT), may be a potential solution. To this end, we developed a tissue-engineered vascular conduit with EHT that allowed surgical implantation into a murine model for in-vivo assessment.

Methods:
Mouse-scale conduits were fabricated from type I collagen using freeform reversible embedding of suspended hydrogels (FRESH) 3D bioprinting. The conduits were cellularized using human stem cell-derived cardiomyocytes and cardiac fibroblasts. Electrophysiology was assessed using calcium imaging. The conduits were surgically anastomosed to the infra-renal inferior vena cava (IVC) as an end-end interposition graft in severe combined immunodeficiency (SCID)/beige mice. The conduit's patency and the EHT's contractility were monitored with monthly ultrasounds. Explanted conduits underwent histology, immunohistochemistry (IHC), and immunofluorescent (IF) imaging.

Results:
Sixteen contractile conduits were produced. In vitro calcium imaging demonstrated anisotropic calcium wave propagation along the conduit at day 14. Twelve grafts were implanted in the mouse IVC and half of the grafts (n=6) were explanted 6 months postoperatively. At explant, five showed synchronous contractile behavior in-vivo of the EHT around the collagen conduit. Interconnected networks of sarcomeric alpha actinin-positive cardiomyocytes were observed on IHC and IF. Neo-vascularization was seen infiltrating the EHT on histology. Six mice remained alive at 11 months post-operatively, three with contractile activity seen via ultrasound. All twelve grafts were patent on ultrasound with no stenosis.

Conclusion:
We have produced mouse-scale pulsatile conduits using human embryonic-derived cardiomyocytes and bioprinting that are robust enough to withstand surgical anastomosis to the IVC and remain patent. We observed functional beating of the EHT at 11 months in vivo. This model could be used to assess and improve the in-vivo function of EHT towards producing a larger-scale pulsatile Fontan conduit.
Abstract 4144487: Fully Ungated, Free-Breathing, 3-Dimentional T2* Mapping for Imaging Hemorrhagic Myocardial Infarction
Authors: Guan Xingmin , Yang Hsin-jung , Sykes Jane , Wang Nan , Zhang Xinheng , Tang Richard , Christodoulou Anthony , Sharif Behzad , Li Debiao , Prato Frank , Dharmakumar Rohan
Published: November 2024

Introduction:
T2* cardiac MRI (CMR) is the standard for detecting hemorrhagic myocardial infarction (MI). However, the conventional T2* CMR (2D breath-held, ECG-gated, multi-gradient-echo T2*) can suffer from limited spatial resolution and multiple motion artifacts. We developed a time-efficient, fully ungated, free breathing, 3D T2* mapping method for detecting and characterizing hemorrhagic MI (hMI).

Methods:
Our approach, developed using a low-rank tensor framework, was tested in a canine model with reperfused hMI. Animals (n=5) underwent CMR 3 days after reperfusion. Short-axis, conventional 2D and proposed 3D T2*-w images, and the corresponding LGE images were acquired in a 3T CMR system. T2* maps (8 echoes, 1.41-15.44 ms) were constructed using mono-exponential fitting. IMH extent was determined by measuring the weighted sum of the imaging slices with hypointense regions (based on ‘mean-2SD’ criterion) within the LGE positive territories. Image quality was assessed by two CMR experts using a Likert scale (1 – poor; and 5 - excellent).

Results:
Figure 1 shows representative conventional 2D, proposed 3D T2* images, along with LGE image for reference. T2* image scores were higher with the proposed than the conventional approach: 3.5 ± 0.5 (conventional) vs 3.8 ± 0.3 (proposed), p<0.05. IMH extent measured using the two approaches provided equivalent IMH extent (see Fig. 2) under stable imaging conditions.

Conclusions:
The proposed 3D T2* mapping can provide much needed improvement in image quality compared to conventional 2D T2* CMR for detection of hemorrhagic MI without the need for breath holding or cardiac gating, both of which are known problems in acute MI patients. Provided imaging conditions are favorable, we also found that the proposed and conventional methods yield equivalent estimates of IMH extent. Additional studies are needed to evaluate the benefits of the proposed approach in clinical setting.
Abstract 4144492: Association of the Intermountain Risk Score with Major Adverse Cardiovascular Events in Patients Assessed for Renal Transplantation
Authors: Horne Benjamin , Minder C , Le Viet , Morris Donald , Anand Sanjiv , Dow Sean , Mason Steve , Anderson Jeffrey , Bair Tami , Knight Stacey
Published: November 2024

Background:
In patients with end-stage kidney disease, assessment of cardiovascular (CV) risk is difficult due to a lack of analytical decision tools to guide care. The Intermountain risk score (IMRS) is a well-validated sex-specific risk prediction tool calculated from weightings of age and components of the complete blood count and basic metabolic profile that was originally derived to predict mortality. IMRS also predicts major CV events. This study evaluated the association of IMRS with major adverse CV events (MACE) in patients listed for renal transplantation (Tx).

Methods:
Patients evaluated for renal Tx between June 2015-April 2024 and subsequently listed were assessed using cardiac PET/CT, echocardiography, and other risk measures. MACE was defined as pre-Tx all-cause mortality, acute MI, or Tx de-listing. IMRS was computed using the 2009 1-year mortality approach and pre-defined sex-specific risk categories were used. Other data included demographics, comorbidities, CV risk factors, mode of dialysis, and a previously-derived 1-year PET risk score (using ischemic burden, coronary artery calcium, myocardial blood flow, transient ischemic dilation, smoking, obesity, diabetes and inpatient). Association with MACE-free survival was evaluated by Cox regression.

Results:
Among 691 patients with IMRS data (200 were missing labs for IMRS), age averaged 55.9±12.0 years (range 20.9-81.0 years) and 34.3% were female. MACE was found in 171 patients. IMRS was associated with MACE (Figure) in univariable analysis (high vs. low IMRS: HR=2.50, 95% CI: 1.44, 4.32, p=0.001; moderate vs. low: HR=1.55, CI: 0.99, 2.42, p=0.055). For high vs. low IMRS, females had HR=2.26 and males had HR=2.61. Analysis showed that 24.7% of the predictive ability of IMRS was explained by the PET risk score, MI and COPD history, and mode of dialysis. IMRS was independently associated with MACE when adjusted for those factors (high vs. low: HR=1.99, CI: 1.14, 3.49, p=0.016).

Conclusions:
IMRS was associated with long-term pre-Tx MACE outcomes in patients assessed for renal Tx. A quantitative tool computable from objective, standardized, and common electronic health record elements, IMRS may be useful alone as a low-cost, low-touch clinical decision tool to evaluate risk in early screening or together jointly as part of a more complete risk assessment with other factors such as the PET risk score, comorbidities, and dialysis data.
Abstract 4144538: Ivabradine in Patients With Postural Orthostatic Tachycardia Syndrome: A Single-Arm Systematic Review and Meta-analysis
Authors: Queiroz Ivo , Tavares Arthur , Barbosa Lucas , Mesquita Cynthia , Fukunaga Christian , Leandro Giovanna , Pimentel Tulio , Monteiro Arthur , Defante Maria Luiza Rodrigues
Published: November 2024

Background:
Postural Orthostatic Tachycardia Syndrome (POTS) is a condition characterized by an excessive increase in heart rate upon standing and other autonomic symptoms. Optimal treatments for this disease are still under research. Ivabradine, a selective inhibitor of the If channel, has emerged as a potential treatment for POTS due to its ability to reduce heart rate without affecting blood pressure. In this context, we conducted a systematic review and meta-analysis to assess the impact of ivabradine on Symptoms in POTS patients.

Methods:
We systematically searched Pubmed, Embase, and Cochrane databases for studies assessing the efficacy and safety of ivabradine in patients with POTS. We calculated event prevalence for binary outcomes and mean value for continuous outcomes, along with 95% confidence intervals (CI). Statistical analysis was performed using R version 4.3.2. A random-effects model was used for all outcomes, and heterogeneity was assessed with Cochrane's Q and I2 statistics

Results:
We included ten studies, comprising 267 patients, of whom 130 (48.68%) were females, with a mean age of 34,68 years, and the heart rate (HR) before ivabradine use ranged between 94.20 and 117.66 bpm. The analysis showed an improvement of symptoms in 90.89% (95% CI: 80.34-98.07;) of patients, and a decrease of 14.46 bpm in HR (95% CI: 7.69-21.24; ), which ranged between 79.82 and 98.25 bpm (95% CI; ). Additionally, we observed side effects events in 9.58% of patients (95% CI: 3.69-17.30;).

Conclusion:
In patients with POTS, ivabradine appears to be a viable treatment option. Further comparative and more powerful studies are necessary to assess the efficacy and safety of ivabradine in this population.
Abstract 4144646: Assessing the Impact of Remote Consultation Strategies on Optimizing Guideline-Directed Medical Therapy in Heart Failure Patients: A Meta-Analysis
Authors: Alzubi Alhasan Saleh , S. Beshr Mohammed , Abdelwahed Abdelrahman Farag , Abuajamieh Maram , Elmesherghi Abdulmoez Fauzi , Ekreer Moad , Alawi Zahra Sayed Jalal , Azlitni Muhab , EL AWAMI MOSTAFA , mohamed Mohamed barakat mohamed , Elfaituri Ahmed , Elhadi Muhammed
Published: November 2024

Background:
Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) improves outcomes and quality of life. It includes renin-angiotensin system inhibitors (ACE inhibitors, ARBs, ARNi, MRAs), beta-blockers, and SGLT2 inhibitors, which reduce deaths and hospitalizations. Many patients are undertreated, with non-optimized regimens. Few studies compare virtual versus in-office visits for GDMT management. This study aims to assess the efficacy of a virtual multidisciplinary GDMT team in optimizing therapy for HFrEF patients.

Methodology:
On March 19, 2024, we conducted searches in PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Virtual Health Library (VHL) to identify relevant clinical trials. We included trials comparing virtual consultations with in-office consultations to optimize GDMT, focusing on changes in the usage of GDMT medications (ACEI/ARBs/ARNIs, MRA, BB, and SGLT2) and cardiac hospitalization rates. We used STATA 18 with a DerSimonian random effects model to calculate effect size. Analyses were performed on pre- and post-data of both groups using odds ratios, and we compared cardiovascular hospitalization rates in the post-data using odds ratios (OR).

Result:
The database search yielded 2,401 studies, of which 8 studies with a total of 15,758 participants were included. There was no statistically significant difference in GDMT usage between in-office and virtual consultations for all drugs. For in-office visits, the OR were: SGLT2, OR 1.30 (95% CI: 0.85 - 1.99); beta blockers, OR 1.13 (95% CI: 0.92 - 1.40); MRA, OR 1.12 (95% CI: 1.05 - 1.19); and ACE, ARB, or ARN inhibitors, OR 1.06 (95% CI: 0.96 - 1.17). For virtual consultations, the OR were: SGLT2, OR 1.72 (95% CI: 0.87 - 3.38); beta blockers, OR 1.61 (95% CI: 0.96 - 2.73); MRA, OR 1.17 (95% CI: 0.98 - 1.40); and ACE, ARB, and ARN inhibitors, OR 1.24 (95% CI: 0.85 - 1.80). There was no statistically significant difference in cardiovascular hospitalization events between virtual and in-office visits, with an OR of 0.74 (95% CI: 0.45 - 1.21).

Conclusion:
There were no differences between the two groups in optimizing GDMT usage. However, GDMT medications remain underutilized in heart failure patients despite their proven benefits in reducing morbidity and mortality. More policies and innovative strategies are needed to optimize their usage. Further investigation is crucial for refining clinical approaches and enhancing patient care.
Abstract 4144685: External validation and comparison with REVEAL 2.0 of the 6-strata system for risk stratification in PAH: are we reinventing the wheel?
Authors: Fauvel Charles , Liu Yongqi , Correa-Jaque Priscilla , Everett Allen , Kanwar Manreet , Vanderpool Rebecca , Sahay Sandeep , Benza Raymond
Published: November 2024

Background:
A recent study from the French Pulmonary Hypertension Network showed that stroke volume index (SVI) or mixed venous oxygen saturation (SvO2) may improve risk stratification at follow-up in pulmonary arterial hypertension (PAH) patients with intermediate-risk (according to the European 4-strata system). This resulted in a refined 6-strata system, associated with a discrimination improvement.

Research Questions:
This 6-strata system has not been externally validated and compared with the U.S. based REVEAL 2.0 risk score.

Aims:
To externally validate the refined 6-strata system and compare its performance with the current REVEAL 2.0 risk score.

Methods:
A harmonized dataset from 8 PAH randomized controlled trials generated in collaboration with the FDA was used for this analysis. The REVEAL 2.0 and the refined 6-strata was calculated for individual patients at first follow-up. The outcome assessed was 1-year all-cause death. Discrimination capacities using C-index and 95% confidence interval were calculated.

Results:
A total of 1,692 PAH patients were included: median age 50 (37, 62) years, mPAP 50 (39, 60) mmHg, PVR 9.0 (6.1, 13.1) WU, 6MWD 393 (330, 441) m, NTproBNP 1,933 (148, 1882) pg/mL. Of these, 99% and 76% of patients classified as strata 1 and 2 (low-risk) by the 6-strata system respectively, were classified as low-risk by REVEAL 2.0. Similarly, majority of patients within the strata 3/4 and 5/6 were classified as intermediate and high risk by REVEAL 2.0, respectively. (
Figure 1
). C-index were 0.73, 95%CI [0.68, 0.78], 0.75, 95%CI[0.70, 0.80] and 0.78, 95%CI[0.73, 0.83] for the 4-strata, 6-strata and REVEAL 2.0 risk scores, respectively. There were no significant survival differences at 1-year between patients from strata 1 to 4 (
Figure 2
).

Conclusion:
This is the first external validation of the modified 6-strata system. Although the discrimination capacities with the 6-strata is higher than with the 4-strata, yet it does not add incremental information regarding 1-year survival compared to REVEAL 2.0 risk score.
Abstract 4144721: The role of Na
+
/K
+
ATPase alpha 1 subunit in the sex-difference-associated high risk of thrombosis
Authors: Li Angela , Yue Hong , Wise Hannah , Li Wei
Published: November 2024

Background:
Significant sex differences in the risk of thrombosis-related diseases such as myocardial infarction, stroke, and venous thromboembolism have been well documented in clinical studies. However, the mechanism for these differences is unknown. The sodium/potassium ATPase (NKA), comprising α and β subunits, is crucial in maintaining the sodium and potassium gradient across the cell membrane. It is known that estrogen upregulates the expression of the NKA α1 subunit, encoded by the
Atp1a1
gene, NKA α1 also acts as the receptor for androgen. We hypothesize that NKA α1 is responsible for the sex difference in the risk of thrombosis.

Methods:
Wild-type (WT) and α1 heterozygous (

α1
+/-

) mice of both sexes, aged 8-12 weeks, were subjected to the FeCl
3
-induced carotid artery injury thrombosis model. WT and

α1
+/-

mice that underwent orchiectomy (ORX) or ovariectomy (OVX) were subjected to the thrombosis study in vivo 8 weeks later. Western blot of platelet lysates was used for mechanistic molecular studies.

Results:
WT female mice had a significantly shorter time to form occlusive thrombosis than males.
Atp1a1
haplodeficiency significantly inhibited 7.5% FeCl
3
-induced thrombosis in male but not in female mice (
Figure 1
).
ATP1A1
heterozygosity significantly reduced platelet ATP1A1 expression in male mice without affecting intracellular sodium concentration. Female mice platelets expressed more α1 than males. OVX or ORX significantly reduced plasma estrogen (17-beta-estradiol) and testosterone levels, with gonadectomy-induced hormone changes being more dramatic in males (
Figure 2
). OVX did not affect thrombosis in female mice, either WT or

α1
+/-

mice. ORX did not affect thrombosis in WT mice; however, it significantly enhanced thrombosis in male

α1
+/-

mice (
Figure 3
). The expression of platelet ATP1A1 was significantly increased in mice that underwent ORX for 8 weeks or under ovariectomy for 8 weeks followed by treating them with estrogen for 1 week.

Conclusion:
ATP1A1 plays an essential role in platelet activation and thrombosis. Both ORX and estrogen treatment significantly increased platelet ATP1A1 expression, consequently diminishing the anti-thrombotic phenotype in the male

α1
+/-

mice. These data suggest that the interaction between NKA α1 and sex hormones plays a pivotal role in thrombosis. Targeting ATP1A1 could be a novel strategy for addressing the sex difference-associated high risk of thrombosis.
Abstract 4144724: Native aortic stenosis progression: a focus on sex differences.
Authors: Springhetti Paolo , Abdoun Kathia , Powers Andreanne , Tastet Lionel , Beaudoin Jonathan , Pibarot Philippe , Clavel Marie-Annick
Published: November 2024

Background:
Paucity of evidence is available on sex-differences in the progression, left ventricular (LV) remodelling and long-term outcome in patients with native mild-to-moderate aortic stenosis (AS) and preserved LV ejection fraction (LVEF).

Objectives:
To assess the sex-differences in the progression, LV remodelling and long-term outcome of native AS.

Methods:
Baseline and follow-up echocardiographic data of patients with at least mild-to-moderate AS [aortic valve area(AVA)≤1.5 cm2, maximum aortic velocity(Vmax) ≥2.5 m/s or mean gradient(MG)≥25 mmHg] were prospectively collected between 2014 and 2019 and retrospectively analysed. Patients with LVEF<50%, or mitral or aortic regurgitation >mild were excluded. AS progression (analysed by annualized progression ratios in echocardiographic parameters), all-cause death, aortic valve replacement (AVR), were investigated stratifying for sex.

Results:
We included 677 patients with a mean age of 70.8±13.2 years, 258 (38.1%) women. During a median 5 years follow-up, 118(17.4%) deaths and 211(32.2%) AVR occurred. After inverse-propensity-weighting (IPW), men had faster progression rate of AS compared to women (MG: mean difference 1.77[1.10-2.43] mmHg/year, p<0.0001; and Vmax: mean difference 9.56[5.7-13.4] cm/s/year, p<0.0001). While women had higher annualized progression ratio in LV mass-indexed (mean difference 2.51[4.56-0.45] mg/m
2
/year, p=0.017), relative wall thickness (mean difference 0.007[0.01-0.003], p=0.039), but lower stroke-volume-indexed (SVi) (mean difference 0.80[1.10-2.43]ml/m
2
/year, p=0.012). Similar results were obtained after 1:1 matching. Relative to women, men presented similar incidence of all-cause mortality (HR 1.07[0.72-1.56], p=0.73) and AVR on competitive risk analysis (IPW-Sub Hazard Ratio SHR 0.93 [0.61-1.41], p=0.74).

Conclusions:
Mild-to-moderate AS in men presented accentuated hemodynamic progression over time; however, women were more likely to develop LV hypertrophic/concentric remodelling accompanied by lower flow. Similar long-term outcomes were observed in men and women. These results emphasize the importance of evaluating LV remodelling and flow pattern in AS, and not only the AS severity. The slower hemodynamic progression of AS observed in women may be linked to their tendency in reducing SVi, due to distinct LV remodelling pattern.
Abstract 4144727:
In vitro
modelling and functional improvement of TNNT2-R141W mutant pediatric dilated cardiomyopathy
.
Authors: NAGASHIMA TOSHIAKI , Miki Kenji , Miyagawa Shigeru
Published: November 2024

Introduction:
Dilated cardiomyopathy (DCM) is a common cardiomyopathy characterized by ventricular dilatation and systolic dysfunction. The TNNT2-R141W mutation is known to cause DCM in both humans and mice and is associated with Ca
2+
desensitization and reduced contractility. However, there are no reports of utilizing patient-derived induced pluripotent stem cells (iPSCs) carrying the TNNT2-R141W mutation, looking at functional improvement after gene replacement. Here, we describe the characteristics of TNNT2-R141W mutant iPSC-derived cardiomyocytes (iPSC-CMs)
in vitro
.

Methods:
Two human iPSC lines were derived from pediatric DCM patient samples, with the TNNT2-R141W mutation (R141W-iPSC), and a R141W-iPSC derived TNNT2 overexpression line (TNNT2-OE iPSC) for comparison. The Ca
2+
handling and sarcomere structures of the differentiated hiPSC-CMs were then assessed.

Results:
In TNNT2-OE iPSC-CMs, the expression level of
TNNT2
was significantly higher than R141W-iPSC-CMs. Evaluation of Ca
2+
handling revealed that R141W-iPSC-CMs exhibited a significant decrease in maximum fluorescence intensity (amplitude) and a prolongation of time to maximum fluorescence intensity (time to peak), which are characteristic of failing heart tissue (Figure 1a, b, and c). Ca
2+
reuptake efficacy during relaxation, measured by Ca
2+
decay tau, or the time taken for an 80% signal reduction, was also significantly prolonged in R141W-iPSC-CMs (Figure 1d). In addition, R141W-iPSC-CMs displayed abnormality in sarcomere alignment (Figure 2). These properties were corrected in TNNT2-OE iPSC-CMs, indicating that R141W-iPSC-CMs reflect DCM phenotypes
in vitro
.

Conclusions:
R141W-iPSC-CMs exhibited Ca
2+
desensitization and abnormal sarcomere structure, further suggesting that gene therapy with normal TNNT2 may be a future therapeutic approach for DCM with TNNT2 mutations.
Abstract 4144734: Effect of Methylprednisolone on Inflammation and Clinical Outcomes in Neonates Undergoing Cardiac Surgery: A Randomized Controlled Trial
Authors: Jin Yu
Published: November 2024

Background:
Corticosteroids are widely used in neonatal cardiac surgery for anti-inflammatory purposes. Previous research has demonstrated that perioperative use of methylprednisolone (MP) leads to a reduced inflammatory response. Nevertheless, the benefit of MP for postoperative clinical outcomes is controversial, especially in neonates. This study aimed to evaluate the effect of MP on postoperative inflammation and outcomes in neonatal cardiac surgery with cardiopulmonary bypass (CPB).

Methods:
From September 2020 to August 2023, 86 neonates who underwent cardiac surgery with CPB were enrolled in this double-blind randomized controlled trial. After anesthesia induction, the MP group received a single dose of 30 mg/kg MP, and the placebo group received an equal volume of saline solution. The primary endpoints were plasma concentrations of interleukins (IL-6, IL-8, and IL-10) and D-dimer. Composite outcomes included death, respiratory infection, cardiac arrest, the need for extracorporeal membrane oxygenation, acute kidney injury, low cardiac output syndrome, and prolonged mechanical ventilation.

Results:
MP did not reduce the odds of a composite outcome (OR, 1.208; 95% CI, 0.515-2.832;
p
= 0.664), which occurred in 25 patients (58.1%) in the MP group and 23 patients (53.5%) in the control group. Consistent with the observed anti-inflammatory effects, MP resulted in significantly lower concentrations of proinflammatory cytokines (IL-6 and IL-8) and higher concentrations of an anti-inflammatory cytokine (IL-10). The postoperative vasoactive inotropic score (VIS) was significantly lower, while postoperative procalcitonin and nadir mixed venous oxygen saturation (SvO
2
) during the first 24 h were distinctly greater in the MP group. No differences in postoperative D-dimer, blood glucose or insulin administration were detected between the two groups.

Conclusion:
Compared with placebo, the prophylactic administration of 30 mg/kg MP to neonates who underwent cardiac surgery with CPB did not improve clinical outcomes. However, a decreased inflammatory response was detected.
Abstract 4144744: Sex difference in Prosthesis-Patient Mismatch after Surgical Aortic Valve Replacement and long-term clinical outcome
Authors: Springhetti Paolo , Abdoun Kathia , Dumont Eric , Dagenais Francois , Kalavrouziotis Dimitri , Mohammadi Siamak , Pibarot Philippe , Clavel Marie-Annick
Published: November 2024

Importance:
Prosthesis-Patients Mismatch (PPM) is associated with multiple adverse event after aortic valve replacement (AVR), especially increased long-term mortality. Despite women are more likely to have PPM, sex-differences in PPM outcomes remain poorly explored.

Objectives:
To evaluate PPM incidence and sex-differences in PPM impact in a large cohort of patients underwent surgical aortic valve replacement.

Design, Setting and Participants:
We included 7,319 patients who underwent Surgical AVR between 2000 and 2021. PPM was defined accordingly to Valve-Academic-Research-Consortium-3 criteria, adopting correction for Body Surface Area >30 kg/m2 and retrieving the predicted effective orifice area of the aortic valve prosthesis. The cohort was followed up prospectively from Surgical AVR until November 2023.

Main Outcomes and Measures:
Primary endpoint was defined as long-term mortality and secondary endpoint as long-term cardiovascular (CV) mortality. Mortality was established and Cardiovascular mortality adjudicated by Quebec national database.

Results.
Severe PPM incidence was rare (1.1%), more prevalent in women (2.5%) than in men (0.5%, p<0.0001). Any-degree-PPM (22.8% of patients) was also more prevalent in women (31.9% vs. 19.7%, p<0.0001). Over a median follow-up of 13 years, there was 3,231 (44.1%) all-cause deaths, with 1,238 (16.9%) being from CV causes. PPM was associated to excess mortality (HR:1.30[1.20-1.40]; p<0.0001) and CV mortality (HR: 1.39[1.23-1.57]; p<0.0001) in the whole cohort without interaction between sexes (p=0.94 and p=0.74). After comprehensive multivariable adjustment, PPM resulted an independent predictor of long-term mortality and CV mortality in women (both p≤0.04) but no in men (both p≥0.66).

Conclusion and relevance:
In this large series of AVR patients, PPM was more prevalent in women, in whom it was an independent predictor of mortality. This finding suggests that sex-specific management of aortic valve intervention may be of importance and warrants further studies focusing on this aspect.
Abstract 4144768: Hypogenesis of Lymphatic Vessels in the Mitral Valve of Fibrillin-1 Mutant Mouse
Authors: TAN CAN , Chiu Stephen , Kume Tsutomu
Published: November 2024

Marfan Syndrome (MFS) is an autosomal-dominant cardiovascular disorder usually associated with the heterozygous mutation in the
FBN1
gene, which encodes fibrillin-1, a structural macromolecule that polymerizes into microfibrils in connective tissue. Fibrillin-1 regulates the bioavailability of transforming growth factor (TGF) β1, a vital cytokine that modulates various cell activities. Enhanced TGFβ signaling induced by
Fbn1
mutation is a major contributor to the MFS pathogenesis, one of which is myxomatous mitral valve degeneration that can cause mitral valve prolapse, with an incidence of about 45% in
FBN1
mutant individuals. There is evidence that fibrillin microfibrils are present in the wall of lymphatic vessels, and that increased expression of TGFβ1 can inhibit lymphatic endothelial cell (LEC) proliferation during wound repair in mouse tail skin. We recently demonstrated the distribution and function of lymphatic vessels in murine mitral valves. However, the effects of
FBN1
mutation on the formation and maintenance of lymphatic vessels in mitral valves have yet to be elucidated. To investigate the distribution and structure of lymphatic vessels in mitral valves of
Fbn1
mutant mice, whole-mount immunostaining labeled with the LEC marker VEGFR3, as well as the endothelial markers CD31 and VE-cadherin, was performed on the mitral valves of adult (6-week-old)
Fbn1
heterozygous mutant mice and their WT littermates. We found that the density of lymphatic vessels and the number of lymphatic branching points in mitral valve leaflets in
Fbn1
heterozygous mutant mice were decreased, accompanied by the discontinued cell-cell junctions in capillary LECs, as compared to the WT littermates. Further investigation revealed that lymphatic vessels were formed in the WT mitral annulus at postnatal day 7 (P7) but not embryonic day 18.5 (E18.5). In contrast, no lymphatic vessels were found in the
Fbn1
mutant mitral annulus at P7. These results suggest that the increased TGFβ signaling pathway due to the
Fbn1
mutation leads to hypoplasia of lymphatic vessels in the mouse mitral valve, which may affect the lymphatic function and therefore be a cause of the mitral valve prolapse. Further studies are underway to determine the lymphatic functions in
Fbn1
mutant mitral valve as well as to analyze the lymphatic vessels in human myxomatous degenerated mitral valve samples.
Abstract 4144782: Identifying Factors Influencing Response to Dual Antiplatelet Therapy in Non-Cardioembolic Ischemic Stroke and Transient Ischemic Attack: A Meta-analysis of Randomized Controlled Trials
Authors: Chi Kuan Yu , Akman Zafer , Lee Pei Lun , Borkowski Pawel , Chowdhury Ishmum , Song Junmin , Chang Yu , Romero Acero Laura , Nanna, MD, FACC Michele , Nanna Michael
Published: November 2024

Background:
While dual antiplatelet therapy (DAPT) has been shown to significantly decrease recurrent stroke in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of non-cardioembolic origin, it comes with a substantial increase in the risk of bleeding.

Research Question:
Do all patients with non-cardioembolic, mild ischemic stroke/high-risk TIA derive benefits from DAPT for secondary prevention?

Aims:
To identify patients who derive attenuated benefit from DAPT to avoid excessive bleeding risk.

Methods:
We searched 6 databases from inception to May 10, 2024 to identify randomized-controlled trials (RCTs) comparing short-term DAPT (up to 3 months) with aspirin for secondary prevention of non-cardioembolic ischemic stroke or TIA. The primary efficacy outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of any stroke, myocardial infarction, and cardiovascular (CV) death, with prespecified subgroups based on participants’ pre-stroke treatment with statins and antiplatelet agents. Secondary efficacy outcomes comprised of recurrent ischemic events and hemorrhagic stroke. Safety outcomes included major bleeding, CV mortality, and all-cause mortality. A random-effects meta-analysis was performed using restricted maximum likelihood method.

Results:
There were 5 RCTs including 27,559 patients. In the unselected population, DAPT significantly reduced MACCE (RR, 0.78; 95% CI, 0.71 to 0.85; I
2
= 0%; Figure 1A), compared to aspirin. However, patients with baseline statin (RR, 0.93; 95% CI, 0.73 to 1.17; I
2
= 0%; Figure 1A) or antiplatelet (RR, 0.91; 95% CI, 0.69 to 1.21; I
2
= 0%; Figure 1A) before index events did not derive benefits from DAPT. While DAPT led to significantly lower recurrent ischemic stroke (RR, 0.74; 95% CI, 0.68 to 0.81; I
2
= 0%; Figure 1B), it resulted in a significantly higher risk of hemorrhagic stroke, major bleeding, and intracerebral hemorrhage, compared to aspirin (Figure 1B). Moreover, the use of DAPT trended toward an increased risk of all-cause and CV mortality (Figure 1B).

Conclusions:
Patients with baseline statin/antiplatelts use may not derive the same benefits from DAPT for secondary prevention of non-cardioembolic ischemic stroke or TIA.
Abstract 4144785: Identification of ARMCX3 as potential mitochondria-related biomarker for pulmonary arterial hypertension using integrated bioinformatics analysis and machine learning
Authors: Zhang Zeying , Liu Qiming
Published: November 2024

Background:
Acquired mitochondrial dysfunction is one of the characteristics of pulmonary arterial hypertension (PAH). Exploring potential biomarkers from mitochondrial perspective may be effective in the diagnosis and treatment of PAH. We aimed to screen for potential mitochondria-related biomarker(s) associated with PAH using integrated bioinformatics approach and machine learning algorithms.

Methods:
On the basis of gene expression profiles of PAH and healthy samples from the GEO database, hub differentially expressed mitochondrial genes were identified Integrated machine learning algorithm and bioinformatics analysis were performed, including functional enrichment analysis, consensus clustering, and weighted gene co-expression network analysis. Then, the potential biomarkers for PAH were accessed by single-cell data analysis, drug prediction, miRNA-transcription factor-mRNA network construction, and receiver operating characteristic curves. Finally, we explored the associations between the hub mitochondrial genes and immune cell infiltration.

Results:
One hub mitochondria gene ARMCX3 was identified. ARMCX3 has strong stability and high accuracy in predicting PAH patients. Single-cell analysis showed that ARMCX3 was highly expressed in pulmonary vascular smooth muscle cells and endothelial cells. Molecular docking and drug prediction showed estradiol is a potential targeted drug for ARMCX3. 127 miRNA-TF-mRNA regulatory relationships were established. Immune cell infiltraion analysis showed that ARMCX3 is correlated with the content of immune cells.

Conclusions:
ARMCX3 was identified as potential biomarker of PAH based on the machine learning algorithms and bioinformatics analysis, which elucidata the molecular mechanisms underlying PAH development.