bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4143897: Monocyte regulation of magnesium during salt sensitivity of blood pressure
Authors: Mutchler Ashley , Demirci Mert , Kirabo Annet
Published: November 2024

Background:
Dietary magnesium (Mg
+2
) deficiency has been linked to hypertension, chronic kidney disease, and cardiovascular disease. High sodium intake and reduced dietary Mg
+2
consumption are associated with elevated blood pressure. We have previously shown a role for monocyte-producing isolevuglandins (IsoLGs) in the pathogenesis of salt-sensitivity of blood pressure (SSBP) and, in a separate study, dietary Mg
+2
deficiency. However, it is unknown whether decreased Mg
+2
contributes to IsoLG-adduct formation in SSBP[DM1] [PA2] . We hypothesized that decreased Mg
+2
transport into monocytes leads to IsoLG-adduct formation during SSBP.

Methods:
In vitro
studies were performed on isolated monocytes from 11 healthy patients treated with normal salt (150mM) and high salt (190mM) and submitted for RNAseq.
In vivo
studies were performed on 9 hypertensive subjects enrolled in an acute inpatient protocol of salt loading (SL) (460mmoL/24 hrs) and salt depletion (SD) (10mmoL/24 hrs, and furosemide 40mg x 3). Isolated PBMCs were analyzed using CITE-seq (cellular indexing of transcriptomes and epitopes). IsoLG-containing classical monocytes were identified using flow cytometry. Pearson correlation was used to analyze the associations. Salt sensitivity index (SSI) is the difference in SL versus SD systolic blood pressure.

Results:
Using an unbiased approach, I utilized the Harmonizome 3.0 database to identify genes involved in Mg
+2
homeostasis. I identified 75 genes and cross-referenced them with our bulk RNAseq data. Analysis of differentially expressed genes demonstrated a downregulation in Mg
+2
transporter 1 (log2FC=-0.44, p-adj=0.01) and cyclin M2 (
CNNM2
) (log2FC=-0.34, p-adj=0.006) with an upregulation of solute carrier family 41 member 1 (log2FC=0.39, p-adj=0.006) in response to high salt media. In our inpatient cohort, baseline monocyte expression of
CNNM2
negatively correlated with SSI (r=-0.72; p=0.045). There was a positive correlation between baseline
CNNM2
with baseline %IsoLG+ classical monocytes, although not statistically significant (r= 0.69; p=0.06). Similarly, there was a trend of negative correlation of baseline %IsoLG+ classical monocytes with increasing SSI, though not significant (r=-0.68; p=0.06).

Conclusions:
Our preliminary findings suggest high salt downregulates Mg
+2
transporters and decreased Mg
+2
transport are potentially associated with monocyte-derived IsoLG-adduct formation, thus exacerbating the inflammatory response in SSBP.
Abstract 4143906: Prophylactic Administration Of Colchicine Mitigates Atrial Fibrillation Vulnerability Post-Catheter Ablation In Rats: Exploring Sex-Specific Variations.
Authors: Attia Abir , Le Quilliec Ewen , LeBlanc Charles-Alexandre , Xiong Feng , Naud Patrice , Xiao Jiening , Roy Colombe , Sirois Martin , Aguilar Martin , Tardif Jean-Claude , Hiram Roddy
Published: November 2024

Background:
Atrial Fibrillation (AF) is the most diagnosed cardiac arrhythmia in clinical practice. Catheter ablation (ABLA) is a method used to manage AF by cauterizing the left atrium (LA) to isolate arrhythmogenic areas. However, ABLA is paradoxically associated with atrial inflammation and AF recurrence, with 10% of patients experiencing recurrence within 30 days and over 50% after 12 months. Studies suggest that AF prevalence is generally lower in women than in men, but females with AF are more prone to severe complications. Colchicine has been proposed for its anti-inflammatory and cardioprotective effects.

Hypothesis:
Early colchicine treatment prevents ABLA-triggered atrial fibrosis, inflammation, and arrhythmogenic substrates.

Methods:
Male and female Wistar rats (225-275g) were randomly assigned to four groups: Sham or ABLA, with or without colchicine treatment (1 mg/kg/day; intraperitoneally) starting 2 hours before surgery. Sham animals underwent surgery without ABLA.
In vivo
electrophysiological studies and echocardiography were performed on days 1 (D1) and 3 (D3) post-ABLA. On D3,
ex-vivo
optical mapping was conducted on Langendorff-perfused hearts, and atrial fibrosis, gene, and protein expression were assessed using Masson's trichrome staining, qPCR, and immunoblotting, respectively.

Results:
ABLA animals displayed a significantly higher susceptibility to atrial arrhythmias compared to Sham animals, and among ABLA rats, females were 20% less vulnerable to AF than males at D3 post-ABLA. The LA from ABLA rats exhibited significantly slowed conduction velocity, increased fibrosis areas, and enhanced levels of inflammatory markers compared to Sham. Colchicine significantly reduced the incidence of AF post-ABLA with more efficacy in females than males. Moreover, colchicine normalized LA conduction, fibrosis, and inflammation in LA ABLA compared to Sham. Consistent with contemporary knowledge about male and female differences in AF incidence, our data suggest that endogenous female sex hormones combined with colchicine administration may contribute to significantly reducing AF incidence.

Conclusion:
Initiating Colchicine treatment prior to ABLA may lower post-ABLA-induced LA inflammation and AF occurrence. Delving into the variances in male and female responses to colchicine intervention could offer new insights into addressing post-ABLA AF incidence.Bas du formulaire
Abstract 4143910: Comparative Outcomes of Cardiogenic Shock in Acute Myocardial Infarction Versus Acute Heart Failure: A Meta-Analysis
Authors: Saravanabavanandan Ragavendar , Venugopal Darshine , Saha Shubhashis , Panchal Viraj , Venugopal Sharini , Al-Tawil Mohammed , Pullatt Raja
Published: November 2024

Introduction:
Clinical trends show a rise in non-ischemic causes of cardiogenic shock (CS), especially acute heart failure CS (AHFCS). Compared to acute myocardial infarction cardiogenic shock (AMICS), AHFCS typically occurs in the context of chronic heart failure with compensatory mechanisms that seem to better withstand hemodynamic disturbances. Given the clinical heterogeneity, we aim to compare the in-hospital outcomes of AMICS and AHFCS to enhance clinical decision-making.

Methods:
We conducted a comprehensive literature search until April 2024 and included 8 studies from PubMed, Scopus, Embase, etc. We used Mantel-Haenszel random effects and inverse variance models to estimate the pooled risk ratio (RR) and mean differences at a 95% confidence interval.

Results:
Patients with AMICS were older by an average of 6.3 years compared to those with AHFCS [p<0.00001]. The AMICS cohort showed an 80% greater risk of using temporary mechanical circulatory support (tMCS) [RR: 1.80; p<0.00001] and an 88% greater risk of using > 1 tMCS [RR: 1.88; p<0.00001] than patients with AHFCS. When categorized by tMCS type, Impella use was notably higher in the AMICS group [RR: 1.65; p<0.0001]. AMICS patients showed a 79% lower risk of undergoing LVAD implantation [RR: 0.21; p=0.03] and 88% lower risk of heart transplantation (HT) [RR: 0.12; p<0.0001] compared to AHFCS cohort. Our meta-analysis revealed no significant differences between the two groups in hospital mortality [RR: 1.13; p = 0.50], length of stay (LOS), vasopressor use, or occurrence of bleeding.

Conclusion:
This pioneering meta-analysis reveals distinct differences in treatment approaches between AMICS and AHFCS. AMICS patients more frequently utilized tMCS but were less likely to receive LVAD or HT. Despite these variations, in-hospital mortality, LOS, vasopressor use, and bleeding remain comparable between the two groups. This emphasizes the critical need for tailored treatment strategies based on CS etiology.
Abstract 4143915: A Case of Double Chambered Right Ventricle Associated with Ventricular Septal Defect- an Overlooked Congenital Heart Disease
Authors: Wang Roy , Abdulfattah Ammar , Palmer Wayne-Andrew , chandrakumar Harshith , Schaible Michael , Allison Elizabeth , Thambireddy Monica , Nnadi Ekenedilichukwu , Nevolina Anna , Gorantla Asher , Budzikowski Adam , Graham-Hill Suzette , Bukharovich Inna
Published: November 2024

Case description:
A 68-year-old man with history of prostate cancer, anal and scrotal squamous cell carcinoma presented to the cardiology clinic with dyspnea on exertion with exercise tolerance limited to 2 flights of stairs. Physical examination showed grade 3/6 holosystolic murmur best heard at the left lower sternal edge. A transthoracic echocardiograph (TTE) revealed an ejection fraction of 65%, prominent muscle bound right ventricular outflow tract obstruction (RVOT) consistent with double chambered right ventricle (DCRV), and a Windsock deformity of the membranous interventricular septum through which there was a VSD with left to right shunting. The maximal pressure gradient across the VSD was approximately 116mmHg. The pulmonary artery systolic pressure was 61mmHg; consistent with severe pulmonary artery hypertension.

Discussion:
DCRV is a rare condition accounting for 0.5 to 2% of congenital heart diseases. It is characterized by abnormal muscle bands that divide the right ventricle into two chambers; a proximal high-pressure and distal low-pressure chamber, leading to progressive right ventricular outflow tract obstruction (RVOT). This condition rarely occurs in isolation and is often ventricular septal defect (VSD), which is seen in up to 90% of DCRV cases. DCRV may go undiagnosed until adulthood. As the degree of RVOT increases, patients present with shortness of breath and decreased exercise tolerance. TTE is an invaluable tool for diagnosing and determining the severity of obstruction through pulsed and continuous wave doppler to measure the gradient across the hypertrophied muscle bundles. Current guidelines recommend surgery in asymptomatic patients with severe right ventricular obstruction with a pressure gradient greater than 40 mmHg between the proximal and distal compartments within the right ventricle. Even though our patient was mildly symptomatic, his significant pressure gradient of 116 mmHg warrants surgical evaluation.

Conclusion:
DCRV is a rare and often overlooked congenital heart disease. The patient, despite mild symptoms, exhibited classic features of DCRV and associated VSD, highlighting the potential for this condition to persist undiagnosed into late adulthood. The presence of severe pulmonary hypertension further emphasizes the importance of early detection and ongoing management to prevent severe complications such as heart failure and sudden cardiac death.
Abstract 4143940: Circulating Mitochondrial DNA: Biomarker and Inflammation Mediator in Cardiac Ischemia/Reperfusion Injury
Authors: Chu Yuxin , Hua Yutao , He Lihao , Chen Yunxi , He Jin , mckinney kameron , young martin , Ballinger Scott , hu hui , Lal Hind , Xie Min
Published: November 2024

Introduction:
Ischemia/reperfusion (I/R) injury occurs after coronary revascularization, contributing to infarct size. Circulating mitochondrial DNA (mtDNA) levels are elevated in acute myocardial infarction (MI) patients, and act as Damage Associated Molecular Patterns (mtDNA DAMP), which are recognized by the Toll-like receptor 9 (TLR9), initiating pro-inflammatory responses. Prior studies have shown that loss of TLR9 prevents I/R injury in isolated mouse hearts. However, mtDNA DAMP levels have not been measured in ST-elevation MI (STEMI) patients, and whether blocking TLR9 in mice can reduce I/R injury remains unknown.

Hypothesis:
MtDNA DAMP levels serve as markers of STEMI related cardiac injury. Blocking the activation of TLR9 will decrease cardiac I/R injury.

Methods:
MtDNA DAMP levels in serum were measured pre- and 24 hours post- PCI in 55 STEMI patients and 37 healthy controls by qPCR. To evaluate the role of TLR9 on I/R injury, ODN2088 was used to block TLR9 receptor, wild type and TLR9 germline KO mice were subjected to close-chest I/R surgery with minimal systemic inflammation. The cardiac systolic function and infarct size were assessed. Immune cells were isolated from the injured left ventricle and spleens and detected by flow cytometry.

Results:
Pre- PCI mtDNA DAMP levels were increased ~200 folds in STEMI patients compared to healthy controls. After PCI, the elevated mtDNA DAMP levels reduced significantly, while the troponin T levels increased, suggesting mtDNA is an early marker of MI. Compared with negative ODN, ODN2088 treatment at reperfusion reduced infarct size and total leukocytes, myeloid cells, neutrophils and TNF-α
+
cells, and a trend of reduced IL-1β
+
cells, and there was no difference in IL-6
+
cells, total macrophages and residential macrophages. Loss of TLR9 in male and female mice significantly reduced infarct size by ~40% and preserved the systolic function. Meanwhile, there is no difference between genders.

Conclusions:
Circulating mtDNA DAMP level is an early marker of STEMI and may predict the success of PCI. Blocking the mtDNA DAMP-TLR9 signaling pathway during reperfusion significantly reduces I/R injury, indicating it is a viable therapy to mitigate cardiac I/R injury after prompt coronary revascularization.
Abstract 4143963: Cardioprotective Role of Sodium-glucose cotransporter 2 Inhibitors in Cancer Patients Undergoing Anthracycline Therapy: A Systematic Review and Meta-Analysis
Authors: Shrestha Abhigan , Adhikari Ashok , Mainali Nischal , Shrestha Sajina , Khandait Harshwardhan , Shrestha Aayush , Khadka Sulochana , Jaiswal Vikash
Published: November 2024

Background:
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are known to have cardioprotective effects in diabetes mellitus and heart failure patients. Anthracyclines, chemotherapeutic agents used in the treatment of various malignancies, carry a high risk of cardiotoxicity and heart failure. The use of SGLT2i to prevent cardiotoxicity and adverse cardiovascular outcomes in cancer patients undergoing anthracycline therapy is not well established.

Hypothesis:
This meta-analysis aims to evaluate the relationship between the use of SGLT2i for the reduction of adverse cardiovascular outcomes in patients undergoing anthracycline therapy.

Methods:
We systematically searched for relevant articles published until March 2024 on PubMed, Cochrane, and Embase. The hazard ratio (HR) was pooled using the random-effects model and a p-value of <0.05 was considered statistically significant.

Results:
Four studies involving 5590 patients (SGLT2i group: 1617 and non-SGLT2i group: 3973) were included in our analysis. The composite outcome, which included heart failure hospitalization, acute myocardial infarction, ischemic stroke, and death was significantly reduced in individuals receiving SGLT2i therapy compared to those who did not receive it (HR: 0.44, 95% CI: 0.27-0.61, I2=0.00%, p<0.005). Moreover, the risk of hospitalization due to heart failure (HR: 0.58, 95% CI: 0.31-0.85, I2=0.00%, p<0.005), and all-cause mortality (HR: 0.51, 95% CI: 0.30-0.72, I2=67.29%, p<0.005) were significantly lower among patients treated with SGLT2i. However, the risk of new heart failure diagnosis (HR: 0.65, 95% CI: 0.27-1.04, I2=0.00%, p=0.86) was comparable.

Conclusion:
The findings suggest that SGLT2i among cancer patients with anthracycline therapy is associated with a lower risk of composite outcomes, heart failure hospitalization, and overall mortality.
Abstract 4143980: Bleeding with the FXI Inhibitor Abelacimab compared with Rivaroxaban in Patients on Antiplatelet therapy: A Prespecified Analysis of the AZALEA-TIMI 71 Trial
Authors: Al Said Samer , Patel Siddharth , Giugliano Robert , Morrow David , Goodrich Erica , Murphy Sabina , Hug Bruce , Parker Sanobar , Chen Shih-Ann , Goodman Shaun , JOUNG BOYOUNG , Kiss Robert , Spinar Jindrich , Wojakowski Wojciech , Weitz Jeffrey , Bloomfield Dan , Sabatine Marc , Ruff Christian
Published: November 2024

Background:
Combining antiplatelet (APT) with anticoagulant therapy increases the risk of bleeding. In AZALEA-TIMI 71, the novel factor XI inhibitor abelacimab reduced the risk of bleeding compared with rivaroxaban in patients with atrial fibrillation (AF). In this analysis, we investigated whether the safety of abelacimab vs rivaroxaban was modified by antiplatelet therapy.

Methods:
AZALEA-TIMI 71 randomized 1,287 patients with AF to abelacimab (90 or 150 mg subcutaneously monthly) or rivaroxaban (20 mg orally daily), with stratification by planned use of concomitant APT. The primary outcome, major or clinically relevant non-major (CRNM) bleeding, was compared using Cox proportional hazards adjusted for age, sex, and BMI, with an interaction term for randomized treatment and APT use.

Results:
Of 1,287 patients, 318 (25%) were on APT at baseline (16% aspirin only, 8% P2Y
12
only, 2% DAPT) and were younger (median age 72 vs 75 years) and had a higher prevalence of CAD (74% vs 40%), prior MI (36% vs 16%) and PAD (15% vs 11%) than those not on APT (p<0.05 for each). The rate of major or CRNM bleeding tended to be higher in those on APT than those not taking APT in the rivaroxaban group (10.6% vs. 7.7%), but not in the abelacimab group (Fig). Both abelacimab doses significantly reduced major or CRNM bleeding compared with rivaroxaban regardless of APT use [60-66% in patients not on ATP and 70-74% in patients on ATP] (Fig). Given the higher rates of bleeding in patients on both rivaroxaban and APT, the corresponding absolute risk reductions with abelacimab tended to be greater in patients on APT (7.1-8.1%) compared to those not on APT (4.6-5.0%) (Fig).

Conclusion:
Inhibition of FXI with abelacimab results in substantial reductions in bleeding compared with rivaroxaban regardless of concomitant APT use. These data support the potential advantage of FXI inhibitors in patients who require concomitant APT.
Abstract 4143986: Non-ischemic septal fibrosis on delayed enhancement CMR provides incremental prognostic value in functional tricuspid regurgitation
Authors: Villar Calle Pablo , Pai Varun , Kochav Jonathan , Chiu Caitlin , Axman Rachel , Sahai Aditya , Reza Mahniz , Ruoli Letizia , Khalique Omar , Mayol Josep , Falco Giorgia , Weinsaft Jonathan , Kim Jiwon
Published: November 2024

Introduction:
CMR enables assessment of cardiac chamber remodeling and associated alterations in myocardial tissue substrate. Primary aim of this study was to examine the relative prognostic utility of chamber remodeling and myocardial tissue alterations in patients with functional tricuspid regurgitation.

Methods:
The population comprised patients with advanced functional TR (≥moderate) undergoing CMR. LGE-CMR was used to identify myocardial scar/infarction inclusive of non-ischemic septal fibrosis (NIsF) which was defined as hyperenhancement in the mid-myocardial or epicardial aspect of the interventricular septum. Clinical characteristics including follow-up and all-cause mortality were obtained blinded to imaging analyses.

Results:
894 pts (71±15yo; 52% male) with advanced functional TR undergoing CMR were studied; LV dysfunction was present in 44% and RV dysfunction in 57%. Paralleling ventricular dysfunction, adverse LV and RV chamber remodeling was also common, occuring in 25% and 43% of the population, respectively. Regarding tissue substrate, over half (50.4%) had LV scar/infarction (9.2±10.8 %LV), 50.8% of which represented NIsF. Prevalence of NIsF was 3-fold higher in patients with concomitant RV dysfunction versus those without (36.1% vs 11.5%, p<0.001). Regarding outcomes, 215 patients died during a median follow-up of 4.6 years. As shown in
Table 1
, LV and RV dysfunction, LV and RV dilation, advanced mitral regurgitation and NIsF were each linked to increased mortality risk (all p<0.001). A combined model incorporating indices known to impact TR prognosis demonstrates NIsF to be independently linked to increased mortality risk even after controlling for RV dysfunction (HR 1.78 [CI 1.31-2.43]; p<0.001). Kaplan-Meier analysis demonstrates significantly increased risk of death in patients with NIsF (p<0.001) (
Figure 1
).

Conclusions:
Among patients with advanced TR, NIsF provides incremental prognostic risk stratification beyond conventional risk markers.
Abstract 4144014: Stress-related genetic factors modify the effect of lower socioeconomic status on cardiovascular disease risk through autonomic and immune mechanisms.
Authors: AbiKaram Krystel , Abohashem Shady , Lau Hui Chong , Khalil Maria , Aldosoky Wesam , Qamar Iqra , Civieri Giovanni , Hanlon Erin , Assefa Alula , Choi Karmel , Smoller Jordan , Seligowski Antonia , Tawakol Ahmed , Osborne Michael
Published: November 2024

Introduction:
Lower socioeconomic status (SES) associates with greater MACE risk in part via stress-related mechanisms. Further, a higher polygenic risk score for neuroticism (nPRS), a marker linked to stress sensitivity and chronic stress conditions, is associated with greater MACE risk. Moreover, individuals with higher nPRS are more susceptible to the cardiovascular impacts of lower SES. Yet, it remains unknown whether individuals with higher nPRS experience greater adverse changes in autonomic and inflammatory intermediaries of stress in the setting of lower SES and whether these changes contribute to MACE risk. Accordingly, we tested the hypotheses that: 1) lower SES links to MACE risk via lower heart rate variability (HRV) and higher C-reactive protein (CRP), and 2) lower SES has a greater impact on HRV and CRP among those with higher nPRS.

Methods:
Individuals (N=18093; median age 64 years; 54% female) with nPRS and SES data were identified in the Mass General Brigham Biobank. SES was assessed as the median income of an individual’s residential zip code with lower income defined as the lowest tertile. Higher nPRS was defined as values ≥ population median. MACE data was collected for 10 years following enrollment using ICD-10 codes. CRP (N=4117) and HRV (N=4412) data were collected from available clinical lab values and electrocardiograms, respectively, with HRV assessed as the standard deviation of all normal RR intervals.

Results:
In the full cohort, both HRV and CRP mediated the relationship between lower SES and MACE risk (p<0.05 for both). In subgroup analyses, CRP and HRV mediated the link between lower SES and MACE among those with higher (but not lower) nPRS (p<0.05) (Figure 1A). Moreover, lower SES associated with both lower HRV and higher CRP, most notably among those with higher nPRS, while those relationships were attenuated among individuals with lower nPRS (Figure 1B).

Conclusions:
Alterations in HRV and CRP appear to be heightened among individuals with higher nPRS and may mediate the association between lower SES and MACE. These findings suggest that the adverse health effects of lower SES are greater among those with genetic risk related to stress sensitivity and stress conditions.
Abstract 4144025: Heparin-Induced Thrombocytopenia among patients with Non-ST Myocardial Infarction increases mortality nearly two-and-a-half times
Authors: Rezvani Robert , Movhaed Mohammad Reza , Hashemzadeh Mehrtash , Hashemzadeh Mehrnoosh
Published: November 2024

Introduction:
Heparin is widely used as anticoagulant in hospitals. It is considered a mainstay of therapy in ST-elevation and non-ST elevation myocardial infarction and is included in the ACLS management of these conditions. Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening immune mediated prothrombotic disorder as a consequence of heparin exposure. This is caused by the production of antibody-heparin/PF4 immunocomplex, which causes platelet activation and aggregation. This study aims to determine the effect of HIT on mortality in patients with non-ST elevation myocardial infarction (NSTEMI).

Research Questions/Aims:
Given the significant morbidity of myocardial infarction, research is needed to identify factors which increase morbidity and mortality. This study aims to determine the mortality of NSTEMI patients with and without HIT.

Methods:
Data was analyzed from available ICD-10 codes from 2016 to 2020. Patients greater than 18 years with ICD-10 codes for NSTEMI with and without HIT were included. The mortality rates were compared between HIT-positive and HIT-negative NSTEMI patients. Patient demographic, clinical, and hospital characteristics were summarized using means and standard deviations for continuous variables, and proportions with 95% confidence intervals for categorical variables. Logistic regression ascertained the odds of binary clinical outcomes relative to patient and hospital characteristics. Multiple logistic regression was used to ascertain the likelihood of the outcome (Odds Ratios (95% CI)) occurring between the characteristics. Analyses were conducted following the implementation of population discharge weights. All p-values were calculated as 2-sided, with a significance level set at p<0.05. Data analysis was performed using STATA 17 (Stata Corporation, College Station, TX).

Result:
We found a significant increase in mortality in NSTEMI patients with HIT vs no HIT for years 2016-2020 (odds ratio [OR] = 2.55, 95% confidence interval [CI] = (2.19-2.98), p < 0.05). In addition, cardiogenic shock was associated in NSTEMI patients with HIT vs no hit (OR = 8.66, CI = (8.43-8.90), P < 0.001)

Conclusion:
This finding suggests that HIT is associated with increased mortality among NSTEMI patients. In the year 2020, COVID-19 infections may have exacerbated the mortality difference observed in years 2016-2019.
Abstract 4144036: Association of PM
2.5
Air Pollution with Inflammatory Biomarkers in Patients with Heart Failure
Authors: Horne Benjamin , Haddad Francois , Anderson Jeffrey , Maecker Holden , Bair Tami , Johnson Mary , Bride Daniel , Muhlestein Joseph , Kim Juyong , Knight Stacey , Nadeau Kari , Knowlton Kirk
Published: November 2024

Background:
Ambient fine particulate matter (PM
2.5
) air pollution is associated with inflammatory conditions in the lungs, heart, and circulation. Inflammation may be causal in poor health outcomes, especially for people with existing disease. This study evaluated the association PM
2.5
levels with concentrations of 115 plasma inflammatory proteins.

Methods:
Patients with heart failure (HF) with preserved ejection fraction (HFpEF, n=44) and HF-free controls (n=35) from the Intermountain INSPIRE registry (NCT02450006) were tested for 115 targeted proteins (EMD Millipore and ELISA). HFpEF cases and controls were stratified by ambient PM
2.5
levels for low (PM
2.5
≤7 µg/m
3
) and higher exposure (PM
2.5
>20 µg/m
3
). PM
2.5
levels on the day of sample collection were evaluated, as well as 3-day and 7-day PM
2.5
moving averages (mAvg) of the concurrent day plus 2 or 6 immediately previous days. Samples drawn on days with PM
2.5
= 7.1-20.0 µg/m
3
were excluded.

Results:
Patients with HFpEF averaged 74.6±11.7 years of age (2.8 years since HF diagnosis) and 65.9% were female (controls: 72.0±8.7 years, 62.9% female). In HFpEF cases (Table), PM
2.5
>20 µg/m
3
on the sample collection day was associated with higher IL-18 (p<0.001 vs. ≤7 µg/m
3
) and C-C motif chemokine ligand 27 [CCL27, also known as cutaneous T cell-attracting chemokine (CTACK)] (p<0.001 vs. ≤7 µg/m
3
), with a trend for TNF-α (p=0.012). The 3-day PM
2.5
mAvg was significant for IL-18 and CCL27, while CCL27 remained significant for the 7-day mAvg (Table). In controls, none of the 115 biomarkers differed based on PM
2.5
levels. Age did not differ in cases or controls by PM
2.5
category.

Conclusions:
In a pilot study evaluating the inflammatory response to air pollution, CCL27 and IL-18 were higher in patients with HFpEF during short-term PM
2.5
elevations. Inflammatory biomarkers were not different based on PM
2.5
levels in people free of HF. Short-term PM
2.5
elevations may induce inflammation and these findings suggest that people with HFpEF struggle to restore homeostasis.
Abstract 4144053: Age- and Sex- Differences in the Accuracy of Rule-based Natural Language Processing Models for Identification of Pulmonary Embolism
Authors: Krishnathasan Darsiya , RASHEDI SINA , Khairani Candrika , Bejjani Antoine , Lo Ying-Chih , Zarghami Mehrdad , Mahajan Shiwani , Caraballo Cesar , jimenez ceja jose victor , Jimenez David , Monreal Manuel , Secemsky Eric , Klok Erik , Hunsaker Andetta , Aghayev Ayaz , Muriel Alfonso , Hussain Mohamad , Appah-Sampong Abena , Aneja Sanjay , MOJIBIAN HAMID , Goldhaber Samuel , Wang Liqin , Zhou Li , Krumholz Harlan , Piazza Gregory , Bikdeli Behnood
Published: November 2024

Background:
Presentation, treatment and outcomes of pulmonary embolism (PE) in adults varies by age and sex. Recently, some rule-based natural language processing (NLP) tools have been developed to detect PE from radiology reports. It is unknown whether variations in age and sex influence the accuracy of the NLP models to detect PE in radiology reports.

Methods:
We used patient data from the Mass General Brigham (MGB) Health System between 2016 and 2021. The NLP models developed by Verma et al. and Johnson et al. were applied to radiology reports to determine PE among a randomly selected sample of 1,712 patients (52.3% female and 45.3% ≥65 years old). Two independent physicians conducted a manual chart review of patient records with predefined criteria, serving as the reference standard. Accuracy metrics were ascertained across age (≥65 vs. <65 years) and sex (female vs. male) subgroups. Weighted estimates were established based on the total number of hospitalizations at MGB (n=381,642, 54.0% female and 47.2% ≥65 years old).

Results:
In the weighted sample, the prevalence of PE was 2.0% (7,708/ 381,642). The weighted estimates of the NLP models resulted in high sensitivity (range 71.0% to 89.3%) and specificity (range 96.8% to 98.6) for patients ≥65 and <65 years of age (Table, Part A). Similarly, both models resulted in high sensitivity (range 76.9% to 88.2%) and specificity (range 96.6% to 98.7%) for females and males (Table, Part B). However, positive predictive values were low for both models in the two age categories (range 36.8% to 51.0%) and sex groups (range 35.1% to 54.7%) (Table, Parts A and B).

Conclusions:
Despite some variations in the accuracy of the rule-based NLP models, positive predictive values across age and sex groups were low. Further improvements are necessary before rule-based NLP tools can be reliably utilized for PE identification from imaging reports.
Abstract 4144056: Quantitative Testing Reveals Severity of Autonomic Dysfunction after Acute COVID-19 Infection: A Comparison with Controls and Autonomic Failure
Authors: Keller Ciana , Mascarenhas Lorraine , Duval Sue , Benditt David
Published: November 2024

Background:
COVID-19 infections have been associated with cardiovascular autonomic dysfunction (AD). Clinical findings include fatigue, cognitive impairment, and postural intolerance. However, quantitative post-COVID AD assessments are lacking.

Objective:
Compare autonomic testing measures of post-COVID-19 subjects to controls and those with pure autonomic failure (PAF).

Methods:
Autonomic testing included 1) change in heart rate (HR) and blood pressure (BP) with active standing (AS) and tilt table testing (TT), 2) time to BP nadir and recovery during AS and TT, 3) Valsalva ratio (VR), and 4) respiratory sinus arrhythmia (RSA). Comparisons between two groups were made using t-tests, Kruskal-Wallis, or chi-square tests. Multivariable linear regression was used to adjust findings for age and sex. A p-value of <0.05 was considered significant.

Results:
Control subjects (n=25, median 32 [21-39] years, 76% female) and post-COVID patients (n=91, median 36 [25-50] years, 84% female, mean 11.96 [±9.14] months from infection) were similar in age and sex, while the PAF group (n=38, median 64 [56-74] years, 53% female) was older and comprised of more males (Table 1). The VR and RSA of the post-COVID group was significantly lower than controls, but higher than the PAF group (Table 2). The change in BP with AS and TT for post-COVID subjects was significantly higher than controls and lower than the PAF group. The post-COVID group also had a significantly increased change in HR with TT compared to both the control and PAF groups. Across all four tests, the post-COVID group had a higher proportion of abnormal results compared to controls. After adjusting for age and sex, post-COVID subjects continued to have a greater change in HR and BP with AS and TT and a lower RSA compared to controls. However, with this adjustment several differences compared to the PAF group were attenuated (Table 3).

Conclusion:
Post-COVID subjects were observed to have multiple quantitative autonomic testing abnormalities. Once corrected for sex and age, AD severity in post-COVID-19 patients is comparable to that seen in neurodegenerative PAF.
Abstract 4144083: AI-CVD: Artificial Intelligence-Enabled Opportunistic Screening of Coronary Artery Calcium Computed Tomography Scans for Predicting CVD Events and All-Cause Mortality: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Naghavi Morteza , Reeves Anthony , Atlas Kyle , Zhang Chenyu , Atlas Thomas , Henschke Claudia , Yankelevitz David , Budoff Matthew , FAN WENJUN , Yu Ruilin , Branch Andrea , Ma Ning , Roy Sion , Nasir Khurram , Molloi Sabee , Fayad Zahi , McConnell Michael , Kakadiaris Ioannis , Zulueta Javier , Maron David , Shah Prediman , Williams Kim , Abela george , Levy Daniel , Wong Nathan
Published: November 2024

Background:
The AI-CVD initiative aims to extract all useful opportunistic screening information from coronary artery calcium (CAC) scans and combines them with traditional risk factors to create a stronger predictor of cardiovascular diseases (CVD). These measurements include cardiac chambers volumes (left atrium (LA), left ventricle (LV), right atrium (RA), right ventricle (RV), and left ventricular mass (LVM)), aortic wall and valvular calcification, aorta and pulmonary artery volumes, torso visceral fat, emphysema score, thoracic bone mineral density, and fatty liver score. We have previously reported that the automated cardiac chambers volumetry component of AI-CVD predicts incident atrial fibrillation (AF), heart failure (HF), and stroke in the Multi-Ethnic Study of Atherosclerosis (MESA). In this report, we examine the contribution of other AI-CVD components for all coronary heart disease (CHD), AF, HF, stroke plus transient ischemic attack (TIA), all-CVD, and all-cause mortality.

Methods:
We applied AI-CVD to CAC scans of 5830 individuals (52.2% women, age 61.7±10.2 years) without known CVD that were previously obtained for CAC scoring at MESA baseline examination. We used 10-year outcomes data and assessed hazard ratios for AI-CVD components plus CAC score and known CVD risk factors (age, sex, diabetes, smoking, LDL-C, HDL-C, systolic and diastolic blood pressure, hypertension medication). AI-CVD predictors were modeled per standard deviation (SD) increase using Cox proportional hazards regression.

Results:
Over 10 years of follow-up, 1058 CVD (550 AF, 198 HF, 163 stroke, 389 CHD) and 628 all-cause mortality events accrued with some cases having multiple events. Among AI-CVD components, CAC score and chamber volumes were the strongest predictors of different outcomes. Expectedly, age was the strongest predictor for all outcomes except HF where LV volume and LV mass were stronger predictors than age. Figure 1 shows contribution of each predictor for various outcomes.

Conclusion:
AI-enabled opportunistic screening of useful information in CAC scans contributes substantially to CVD and total mortality prediction independently of CAC score and CVD risk factors. Further studies are warranted to evaluate the clinical utility of AI-CVD.
Abstract 4144084: Enhanced External Counterpulsation as a Novel Treatment for Heart Transplant Candidates with Ischemic Heart Failure with Reduced Ejection Fraction
Authors: Ali Asif , Farooqui Sami , Khalid Emad
Published: November 2024

Introduction:
Enhanced External Counterpulsation (EECP) is a noninvasive outpatient therapy designed to improve arterial health, cardiac efficiency, and coronary collateral formation by applying sequential external pressure aligned with the patient’s cardiac cycle. It is primarily indicated for refractory angina that is not amenable to PCI or CABG with the opinion of a cardiologist. EECP can improve exercise tolerance, reduce anginal symptoms, and enhance endothelial function, offering a potential alternative for patients with ischemic HFrEF awaiting heart transplantation.

Description of a Case:
A 58-year-old Hispanic female with a history of severe CAD, type II DM, hyperlipidemia, and CVA. A transthoracic echocardiogram (TTE) revealed a dilated LV with an EF of 20%, left atrial enlargement, severe mitral regurgitation, moderate tricuspid regurgitation, right ventricular systolic pressure of 42 mm HG, trivial pericardial effusion, akinesis of the inferior wall, and hypokinesis of the anterior wall. Despite being a heart transplantation candidate, she declined revascularization and sought alternative treatments for angina, dyspnea, and daily activity limitations. The patient underwent EECP, consisting of 35 one-hour sessions over seven weeks. Following EECP, the patient demonstrated improvements in her Canadian Cardiovascular Society angina score (IV to I), New York Association class (IV to I), six-minute walk test performance, and EF (increased to 55%, observed from TTE). Due to these improvements, she was delisted for heart transplantation.

Discussion:
This case illustrates the potential of EECP as an effective noninvasive treatment for patients with symptomatic ischemic HFrEF who are awaiting heart transplantation but are ineligible or unwilling to undergo surgical interventions. Not only did EECP improve the patient's angina and functional status, but it also enhanced her cardiac function. Based on the findings of this case report, further studies should be done to expand the indications of EECP to include HF and other similar patient populations. EECP may alleviate the need for heart transplantation through its integration as a standard early intervention.
Abstract 4144113: Comparative Safety and Efficacy of Transfemoral versus Subclavian Approaches in Transcatheter Aortic Valve Implantation: A Meta-Analysis
Authors: Elfaituri Ahmed , Faraj Hazem Abdelkarem , Alzubi Alhasan Saleh , Khaled Ala , Elfaituri Muhammed
Published: November 2024

Background:
Transcatheter Aortic Valve Implantation (TAVI) is a minimally invasive procedure for high-risk aortic stenosis patients. While the transfemoral approach is traditionally preferred, the subclavian route is gaining recognition as a feasible alternative when transfemoral access is not viable. However, a detailed comparison of the safety and efficacy between these two approaches is not well-established.

Objective:
This meta-analysis aims to rigorously compare the safety and efficacy of the transfemoral and subclavian approaches in TAVI procedures.

Methods:
A comprehensive literature search was performed across PubMed, EMBASE, Cochrane Library, and Scopus databases up to December 2022. Studies that compared the transfemoral and subclavian TAVI approaches to various clinical outcomes were included. Statistical analyses were conducted using R software (version 4.0.3) with metafor and meta packages, and results were synthesized using Odds Ratios (OR) within a random-effects model framework.

Results:
The search identified 11 relevant studies involving 11,787 patients (10,740 transfemoral TAVI and 1,047 subclavian TAVI). Comparative analysis revealed no significant differences between the two approaches in procedure success (OR 1.36; 95% CI 0.86-2.15; P=0.19; I2=0%), in-hospital mortality (OR 0.77; 95% CI 0.45-1.31; P=0.33; I2=0%), 30-day mortality (OR 1.07; 95% CI 0.75-1.52; P=0.71; I2=0%), stroke incidence (OR 0.89; 95% CI 0.55-1.47; P=0.67; I2=0%), vascular complications (OR 1.26; 95% CI 0.67-2.39; P=0.47; I2=68%), significant bleeding events (OR 0.79; 95% CI 0.49-1.26; P=0.32; I2=0%), and myocardial infarction rates (OR 0.49; 95% CI 0.19-1.32; P=0.16; I2=0%).

Conclusion:
This meta-analysis demonstrates that both transfemoral and subclavian TAVI approaches offer comparable safety and efficacy profiles. The choice of approach should be individualized based on patient characteristics, operator expertise, and resource availability. The absence of significant differences and the broad confidence intervals highlight the need for larger, randomized trials to validate these findings further and explore potential clinical nuances.
Abstract 4144135: The Pulmonary Resistance-Compliance Relationship: Real or Mathematical Artefact?
Authors: Hungerford Sara , Kapur Navin , Rich Stuart , Burkhoff Daniel
Published: November 2024

Background:
It has previously been suggested that pulmonary vascular resistance (PVR), the steady component of VA, and arterial compliance (PAC) are physiologically and inexorably linked through an inverse hyperbolic relationship and that their product, the pulmonary vascular time constant (τ), is roughly equal across a range of disease states. A critical and often overlooked concern, however, emerges from the way PAC has come to be estimated in many realms of clinical reearch as the ratio of stroke volume (SV) to pulse pressure (PA
PP,
PAC
clinical
). We sought to explore the foundation of the reported link between PVR and PAC because they both share the value of SV in their determination.In other words, plotting a parameter that is dependent on SV (i.e., PVR) versus another that is dependent on 1/SV (i.e., PAC
clinical
) is inherently prone to yield a hyperbolic relationship.

Methods:
We performed both joint density analysis (JDA) as well as a simple set of simulations using hemodynamic data from a cohort of patients with PH from left-sided disease. PAC
clinical
was calvulated as SV/PA
PP.
PVR was calculated as:

(PA
M
– PCWP)/CO

, expressed in Wood Units. Log values were plotted to determine PVR-PAC
clinical
relationships.

Results:
JDA of predicted PVR against PAC
clinical
demonstrated a Spearman’s R of -0.88 (CI -0.92 to -0.82). With bootstrapping, this increased to -0.92 (CI -0.93 to -0.91) demonstrating very high mathematical correlation and precision (Figure 1a). Hemodynamic model simulation demonstrated a consistent inverse dependence characterized by a first-order hyperbolic decay function (

PAC = τ
avg
/PVR

; r
2
0.86; p<0.001; Figures 1b-d). Compared with data from points associated with lower PCWP, the log
10
-transformed relationship was shift downward in a nearly parallel manner (Figures 1e-g).

Conclusions:
By performing JDA, as well as creating a random, albeit physiologically constrained hemodynamic simulation, we were able to recreate, with high-fidelity, the inverse hyperbolic relationship between PVR and PAC
clinical
reported in prior studies and the effect of PCWP on this relationship. Re-exploration of the PVR-PAC relationship, using more accurate methods of PAC determination, is now required to understand whether this relationship is truly physiological, or simply, mathematical artefact.
Abstract 4144145: Mavacamten-induced Augmentation of Exercise Strain is the Mechanical Basis for Improvement in Exercise Capacity in Obstructive Hypertrophic Cardiomyopathy
Authors: Herry Morgane , Mao Chun-Tai , Abraham Maria Roselle , Abraham Theodore
Published: November 2024

Background
: Mavacamten reduces left ventricular outflow tract gradients (LVOTg), improves symptoms and increases exercise capacity in symptomatic obstructive hypertrophic cardiomyopathy (oHCM) patients. We investigated the potential myocardial mechanical basis for improved exercise capacity in these patients.

Methods:
We evaluated symptoms, exercise capacity in metabolic equivalents (METs), LVOTg at rest, at Valsalva and peak-exercise, and global left ventricular longitudinal strain (GLS) at rest and peak-exercise in patients before and during mavacamten therapy.

Results:
oHCM patients at a single tertiary center (n=22, 56% female, mean age 64 ± 12 years) were evaluated pre- and post-mavacamten initiation (Table). Mean duration of treatment was 22 ± 14 weeks. There was significant improvement in NYHA class – proportion of NYHA I increased from 0 to 64% and NYHA II and III decreased from 77 to 34% and 23 to 5%, respectively (Figure B). All patients underwent a symptom-limited Bruce protocol treadmill stress echocardiogram and there was a significant improvement in exercise capacity pre- vs. on-mavacamten (7.6± 3.4 vs. 8.6± 3.4 METs, respectively, p 0.01). There was a significant decrease in LVOTg at rest, at Valsalva and post-exercise (47 ± 43 vs. 9.8 ±6 mmHg, 82 ± 46 vs 20 ± 19 and 114 ± 54 vs. 43 ± 40 mmHg, respectively, all p < 0.001). Rest GLS did not change pre- vs. on-Mavacamten (15 ± 3 vs. 16 ± 3%, p 0.07). However, peak-exercise GLS improved significantly (16 ± 4 vs. 18 ± 4%, pre vs. on-mavacamten, p < 0.01) (Figure A).

Conclusion:
Mavacamten-induced augmentation of exercise strain may be the mechanical basis for exercise capacity improvements in oHCM. Rest GLS non-significantly increased on mavacamten. Our results will need validation in a larger cohort.
Abstract 4144157: Coronary microvascular disease has subtypes with distinct wave intensity profiles as measured with intra-coronary provocation agents
Authors: Carrington Justin , Lerman Amir , Raphael Claire
Published: November 2024

Background:
Coronary microvascular disease (CMD) may be endothelium-independent (coronary flow reserve, CFR<2.5) or endothelium-dependent (<50% increase in coronary blood flow in response to acetylcholine). Endothelium-independent CMD has been subclassified into structural and functional groups based on hyperemic microvascular resistance (hMR, mmHg/cm/s). We hypothesized that endothelium-dependent CMD also has these subtypes.

Methods:
Patients with non-obstructive coronary artery disease who underwent coronary catheterization of the left anterior descending artery were included (n=112). Pressure and flow were recorded at rest, with adenosine, and with acetylcholine. Patients were classified by endothelial type and functional CMD (hMR<2.5) or structural CMD (hMR>2.5). Wave intensity analysis was performed and cumulative separated wave intensity (Joules/m
2
) was calculated by standard formulae. Three dominant waves were analyzed (forward compression wave, FCW; backward compression wave, BCW; backward expansion wave, BEW).

Results:
Seventy-four of 109 patients had CMD, of which 59 had endothelium-independent and 38 had endothelium-dependent CMD (23 had both). Functional and structural subgroups were identified (Figure 1). All CMD subtypes had significantly different wave intensities at rest, adenosine, and acetylcholine (p<0.05). Comparing subtypes, there was no difference in wave intensities at rest. However, wave intensities significantly differed between all CMD subtypes with adenosine and acetylcholine, with higher energy waves in the endothelium-independent and functional groups (p<0.05, Figure 2).

Conclusions:
CMD is a heterogenous condition with distinct subtypes. Functional and structural groups exist in both endothelium-dependent and endothelium-independent CMD. These subgroups have distinct hemodynamic profiles as measured by wave intensity. A patient-specific approach to first line medical therapy may be improved by subgroup classification.