United States

Abstract Title
Postoperative Opioid Use for Regional vs. General Anesthesia in Hip Arthroplasty
Background
Total hip arthroplasty is a commonly performed surgical procedure, especially among elderly patients. Effective anesthesia management significantly influences outcomes and reduces complications. The choice between regional anesthesia (RA) and general anesthesia (GA) remains a subject of ongoing debate. This comprehensive database study aims to compare long-term postoperative opioid usage for pain management between patients who received general anesthesia versus regional anesthesia.
Methods
The study utilized the TriNetX database, comprising deidentified patient information for over 124 million individuals. Subjects with at least two years of follow-up electronic health data were included in the regional (Bupivacaine) and general (Propofol) anesthesia groups. The study focused on patients who underwent total hip arthroplasty (THA) under anesthesia from 2015 to 2021. Propensity score matching was employed in a 1:1 ratio to balance outcome-affecting variables between the two cohorts. Postoperative opioid use was compared across 90 days, 1 year, and 2 years. Statistical analysis, including odds ratios (ORs) and 95% confidence intervals (CIs), was conducted using the TriNetX database.
Results
A total of 253,827 patients underwent THA under anesthesia, with 112,206 under regional anesthesia and 150,930 under general anesthesia. Propensity score matching resulted in 112,205 patients in both the regional and general anesthesia groups. Following matching, statistical analysis revealed no significant differences in opioid use between regional and general anesthesia groups at 90 days [(OR (95% CI), 1.17 (0.96, 1.425)], 1 year [OR (95% CI), 1.123 (0.983, 1.284)], and 2 years [OR (95% CI), 1.105 (0.991, 1.232)].
Conclusion
The findings suggest that regional anesthesia does not provide superior postoperative pain control with reduced opioid consumption compared to general anesthesia. However, regional anesthesia may lead to shorter hospital stays for these patients. Clinicians should consider these results when customizing anesthesia strategies for individual patients, aiming to achieve the most suitable plan based on each patient&#39;s specific needs.

AMA Research Challenge 2024 

Postoperative Opioid Use for Regional vs. General Anesthesia in Hip Arthroplasty

Abstract Title
Postoperative Opioid Use for Regional vs. General Anesthesia in Hip Arthroplasty
Background
Total hip arthroplasty is a commonly performed surgical procedure, especially among elderly patients. Effective anesthesia management significantly influences outcomes and reduces complications. The choice between regional anesthesia (RA) and general anesthesia (GA) remains a subject of ongoing debate. This comprehensive database study aims to compare long-term postoperative opioid usage for pain management between patients who received general anesthesia versus regional anesthesia.
Methods
The study utilized the TriNetX database, comprising deidentified patient information for over 124 million individuals. Subjects with at least two years of follow-up electronic health data were included in the regional (Bupivacaine) and general (Propofol) anesthesia groups. The study focused on patients who underwent total hip arthroplasty (THA) under anesthesia from 2015 to 2021. Propensity score matching was employed in a 1:1 ratio to balance outcome-affecting variables between the two cohorts. Postoperative opioid use was compared across 90 days, 1 year, and 2 years. Statistical analysis, including odds ratios (ORs) and 95% confidence intervals (CIs), was conducted using the TriNetX database.
Results
A total of 253,827 patients underwent THA under anesthesia, with 112,206 under regional anesthesia and 150,930 under general anesthesia. Propensity score matching resulted in 112,205 patients in both the regional and general anesthesia groups. Following matching, statistical analysis revealed no significant differences in opioid use between regional and general anesthesia groups at 90 days [(OR (95% CI), 1.17 (0.96, 1.425)], 1 year [OR (95% CI), 1.123 (0.983, 1.284)], and 2 years [OR (95% CI), 1.105 (0.991, 1.232)].
Conclusion
The findings suggest that regional anesthesia does not provide superior postoperative pain control with reduced opioid consumption compared to general anesthesia. However, regional anesthesia may lead to shorter hospital stays for these patients. Clinicians should consider these results when customizing anesthesia strategies for individual patients, aiming to achieve the most suitable plan based on each patient's specific needs.

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Background: A hemodynamically significant patent ductus arteriosus (HSPDA) is a common concern in the care of premature infants, but its definition remains a challenge and its preferred treatment remains controversial. 

Methods: We sent an electronic survey to the members of the AAP Sections on Neonatal and Perinatal Medicine, Cardiology and Cardiac Surgery and the PediHeartNet online community regarding their diagnosis and treatment of the HSPDA in premature infants.

Results: 382 neonatologists and 124 pediatric cardiologists completed the survey. Formal echocardiographic and clinical scoring systems for PDA were used infrequently (22.1% and 15.5%). Neonatologists and pediatric cardiologists had significantly different (P<0.001) perceptions of the importance in 11 of 14 echocardiographic parameters used to determine a HSPDA. Surgical ligation was less frequently recommended than catheter closure.

Conclusion: This survey reflects the current best practice in the care of HSPDA and suggests an emphasis on imaging based on clinical condition with formal scoring systems used infrequently.. The difference in perceived value of various echocardiographic parameters between neonatologists and cardiologists may contribute to uncertainty in the determination of HSPDA. Despite being a relatively new technology, catheter occlusion of the HSPDA is recommended more frequently than surgical ligation by this cohort.

A Survey Regarding the Care of the Hemodynamically Significant Patent Ductus Arteriosus (HSPDA)

Background
Bicuspid aortic valve (BAV) is the most common congenital heart condition. BAV complications include aortic valve surgery, aortic surgery, infective endocarditis, and aortic dissection. Due to its 10% chance of transmission to offspring and lifetime morbidity burden of >80%, screening of first-degree relatives is recommended for early detection. Several barriers to echocardiographic screening for BAV have been identified, therefore, a cheap and fast “rule-out” BAV tool is appealing. The objective of our study is to create an artificial intelligence (AI)-enabled electrocardiogram (ECG) model to aid the detection of BAV in suspected individuals.
Methods
Between January 1, 1990, and June 30, 2023, 13,066 adults [mean age 58.3±17 years, 46.6% women] with both an ECG and an echocardiographic study within 6 months of each other, were identified from the Mayo Clinic database. Cases were selected as patients with a confirmed BAV diagnosis either by echocardiographic or pathologic report. Controls were selected as patients with an ECG indication of abnormal auscultation, rule out, suspected, or family history of BAV. Patients were excluded if they displayed any of the following criteria: a previous heart surgery or procedure, potential cardiac remodeling conditions(cardiomyopathies, history of chemotherapy or radiation, autoimmune disease, previous known congenital heart disease, heart failure, myxomas, history of endocarditis, rheumatic heart disease, heart transplant and pacemaker). ECGs by patient were randomly shuffled into mutually exclusive training (80%), internal validation (10%), and test (10%) data sets. A convolutional neural network was built using the Keras Framework under Tensorflow backend (Google;Mountain View,CA,USA).
Results
BAV prevalence in the model’s development was 45%. In the test group, the AI-enabled ECG model achieved an area under the curve (AUC) of 0.704 with the following values: sensitivity 65%, specificity 64.8%, accuracy 64.9%, positive predictive value (PPV) 60.1%, and negative predictive value (NPV) 69.4%.
Conclusion
An AI-enabled ECG model has shown modest diagnostic performance in detecting BAV. When assuming a prevalence of 10% (chance of transmission to offspring), the NPV increases to 94.3% with decreased PPV of 17%. This approach could save a major number of echocardiograms for “ruling-out” BAV, but needs external validation.

Artificial Intelligence-Enabled Electrocardiogram Model for Screening of Bicuspid Aortic Valve

Single ventricle surgical palliation with a Glenn surgery universally leads to unintended pulmonary vascular remodeling with pulmonary arteriovenous malformations (PAVMs) and aortopulmonary collaterals (APCs). The pathogenesis of PAVMs and APCs after Glenn is poorly understood, and published literature is limited. Our research team identified increased macrophages in lung biopsies from patients prior chronic Glenn circulation. Most recently we also identified increased lung macrophages and decreased lung lymphocytes in a surgical animal of Glenn circulation. Because lung macrophages and lymphocytes can originate from the bone marrow and circulate in peripheral blood as monocytes and lymphocytes, we hypothesized that peripheral blood samples from patients with chronic Glenn circulation would demonstrate increased monocytes and decreased lymphocytes compared to age-matched controls. We conducted a retrospective cohort study of patients 0-17 years old who underwent cardiac surgery between 1/1/2012 - 1/1/2024. To assess peripheral blood leukocyte counts, we recorded cell counts from pre-operative complete blood counts (CBC) from patients prior to single ventricle palliation (pre-Glenn and pre-Fontan). We also included age-matched control groups (pre-tetralogy of Fallot surgery and pre-atrial septal defect surgery) because normal leukocyte counts are known to change with age. Patient cohorts were identified through an institutional surgical database and CBCs were recorded through manual chart review immediately prior to the date of surgery. We identified a total of 736 pre-surgical CBCs, including 420 single ventricle CBCs (208 [28.3%] pre-Glenn, 212 [28.8%] pre-Fontan) and 316 control CBCs (156 [21.2%] pre-ASD, 160 [21.7%] pre-TOF). There was no difference in years of age at surgery between our age-matched groups (pre-Glenn 0.35 [0.28, 0.45] vs pre-TOF 0.35 [0.21, 0.50]; p>0.99) (pre-Fontan 3.5 [3.0, 4.1] vs pre-ASD 4.3 [3.0, 7.1]; p=0.19). Compared to their respective age-matched control groups, the pre-Fontan group had increased absolute monocytes (p<0.0001), whereas the pre-Glenn group was not different (p=0.57). Surprisingly, both single ventricle groups had decreased absolute lymphocyte counts (both p<0.0001) and increased absolute neutrophil counts (both p=0.01) compared to their respective control groups. In our single institutional study, chronic Glenn circulation is associated with increased monocytes and decreased lymphocytes in peripheral blood compared to an age-matched control group with an isolated ASD. Further investigation is needed to determine whether peripheral blood leukocyte counts may serve as a biomarker to predict clinical outcomes.

Assessment of leukocyte dysregulation in single ventricle congenital
heart disease

Association Between Pulmonary Artery Catheterization (PAC) Mortality, Length of Stay, and Cost utilizing a National Electronic Health Record Database in 2020


Samuel Y Huang1
1 Icahn School of Medicine At Mount Sinai and Mount Sinai South Nassau, Oceanside, NY, United States of America


Abstract

Importance
Pulmonary artery catheters (PACs) play a pivotal role in managing acute hemodynamic decompensation, allowing for the assessment of right and left ventricular hemodynamic parameters and can allow for determination of SVO2 over echocardiogram. However, because of their invasive nature, increased understanding of their overall benefits is important. In certain populations with decrease compliance such as in patients with ischemia, information from PACs may be hard to utilize.

Aim
This study focuses on evaluating the impact of Pulmonary Artery Catheterizations (PAC) in patients with heart failure and ischemia admitted to the inpatient setting to discern whether PAC usage is associated with increased in hospital mortality rates, prolonged length of stay, costs, and complications. A subgroup analysis will be performed to see if there is a change in outcomes in individuals with and without cardiogenic shock as well as in individuals with mechanical circulatory support devices such as Intra-aortic balloon pumps (IABP), intraoperative Extracorporeal mechanical oxygenation (ECMO), mechanical ventilation, and renal dialysis. 

Objective
The utilization of pulmonary artery catheters (PACs) in guiding decision-making for the management of cardiogenic shock is a common practice. However, despite their widespread use, there is a paucity of robust evidence delineating the optimal application of PACs in the context of cardiogenic shock. The existing literature lacks conclusive support for the efficacy and benefits of obtaining hemodynamic data through early PAC placement in patients experiencing CS. This study seeks to address this gap by rigorously examining the association between early PAC placement and pertinent clinical outcomes, aiming to contribute evidence that can inform and optimize the management of cardiogenic shock.


Design, setting, and participants
This retrospective study utilized the National Inpatient Sample (NIS) data for the year 2020, focusing on patients with heart failure and diagnosis of ST elevation myocardial infarction (STEMI) with description of those experiencing cardiogenic shock, individuals receiving intra-aortic balloon pumps (IABPs), undergoing mechanical interventions, and those treated with extracorporeal membrane oxygenation (ECMO). Additionally, the study included patients who underwent Pulmonary Artery Catheterization (PAC).
Methods
ICD-10 codes lung cancers were identified from the American Medical Association Complete Official Handbook. Heart failure, Ischemia, and pulmonary artery catheterizationss ICD-10 codes. Multivariable linear regression and logistic regression models were employed, incorporating Charlson comorbidity, age, gender, race, and cardiogenic shock, to assess the impact of catheterization on length of stay, healthcare costs, and mortality in patients with heart failure, ischemia, and cardiogenic shock. Additionally, a Kaplan-Meier analysis was conducted to evaluate the time to 30-day discharge for patients who underwent catheterization, considering demographic variables and cardiogenic shock as potential influencing factors. 

Results
The final minimal dataset comprised a total of 114,647 individuals who had both congestive heart failure and ischemia, with a mean age of 70.66 years (SD = 13.37). Among these patients, 11.47% (13,147 individuals) experienced mortality. Females constituted 42.19% of the cohort. The mean length of hospital stay (LOS) for this population was 7.16 days (SD = 8.64). Notably, 5.52% of patients received pulmonary artery catheterization (PAC). Upon multivariable analysis pulmonary catheterization was associated with a 18% decreased mortality (95% CI: 0.76 – 0.89, pvalue < 0.001), increase length of stay of 2.1 days (95% CI 1.88 to 2.32, p<0.001), and increased cost of $20,150.37 (95% CI $19,109.28 to $21,191.46, pvalue < 0.001).

Conclusion
Using a nationally representative sample and a large dataset, pulmonary artery catheterizations in patients with congestive heart failure and a diagnosis of STEMI who received a PAC was associated with decreased mortality, increased length of stay and increased cost. Further studies are needed to characterize causation and to apply for each specific region and population of interest.

Association Between Pulmonary Artery Catheterization (PAC) Mortality, Length of Stay, and Cost utilizing a National Electronic Health Record Database in 2020

Background
Mobile low-dose computed tomography (LDCT) lung cancer screenings (LCS) are part of an outreach program in rural Appalachia to detect early malignancy in areas with limited healthcare access. While the primary goal is to screen for lung cancer, LDCT LCS can identify calcium deposits in coronary arteries and can prompt risk modification strategies for prevention of cardiovascular disease (CVD) events. There is no clear guidance for follow-up regarding CAC or prevention of associated CVD risk in patients undergoing LDCT LCS. The aim of this study was to determine how many patients with no known CVD had the presence of CAC on LDCT LCS. Secondary objectives were to determine if patients with CAC scores ≥100 received appropriate CVD risk reduction follow-up, and if initiation of statin or aspirin therapy occurred within 3 months after LDCT LCS. 

Methods
A retrospective review of mobile LDCT LCS from September 2021 to December 2022 was conducted in one large, tertiary health-system. Adult patients with no previous CVD history were included. CT images were obtained at 100 kVp with a slice thickness of 3 mm. Agatston CAC scoring was completed retroactively. Descriptive statistics and chi-square analyses were utilized.

Results
A total of 526 LDCT LCS were included. Over 54% of patients had coronary calcification on LDCT lung screening. 161 patients (30.6%) had a CAC score of ≥100 and 75 patients (14.3%) had a CAC score ≥400. Of patients with a CAC score ≥100, only 7.5% received referrals for follow-up and 9.3% had additional cardiac testing. Of those with a CAC score ≥100 not already on a statin (45.3%), only 8.2% were initiated on statin therapy within 3 months after LDCT LCS. Of those with a CAC score ≥100 not already on aspirin therapy (63.3%), only 5.9% were initiated on aspirin therapy within 3 months after LDCT LCS. Aspirin and statin initiations were dependent on calcium score (p<0.01).

Conclusion
In patients with no CVD history, CAC was frequently identified on mobile LDCT LCS in rural communities. Calcium scoring from LDCT lung screenings allowed for simultaneous assessment of lung cancer and CVD risk. Despite high CAC scores, there was limited initiation of cardiovascular disease prevention measures and follow-up, likely indicating missed opportunities for early intervention. Awareness of CAC score utility, follow-up for identified coronary calcification, and consideration of primary prevention medications when indicated, would be beneficial in patients undergoing LDCT lung cancer screenings, especially in rural areas with limited resources.

Cardiovascular Risk Reduction Strategies After Coronary Artery Calcium Scoring on Mobile CT Lung Screenings in Rural Appalachia

Background
Cardiovascular disease (CVD) is the leading cause of mortality worldwide in both men and women, which is due in part to high prevalence of hypertension. Recent evidence suggests supine, standing, and possibly change in supine to standing blood pressure (BP) may have greater utility to predict future mortality risk compared to the traditionally assessed resting seated BP. We hypothesized that supine, standing and change from supine to standing SBP would have predictive value of all-cause mortality for both men and women.
Methods
The Ball State Adult Fitness Longitudinal Lifestyle (BALL ST) cohort was used for this analysis. The population consisted of 2,116 apparently healthy men and women with no known disease where BP measurements were acquired in the standing and supine positions and the change in supine to standing was calculated. The mean age was 46.2±13.0 yr for men and 44.8±13.2 yr for women. Participants were followed for an average of 18.2±9.0 yr for all-cause mortality. Additionally, measurements of traditional risk factors were obtained. Hazard ratios (95% CIs) were generated for association between BP (supine, standing, change) and all-cause mortality by sex. Multiple Cox proportional hazard models were fit to the following data: 1) BP unadjusted, 2) BP adjusted for age and testing year, 3) BP further adjusted for risk factor (obesity, hypertension, dyslipidemia, diabetes, physical inactivity, and smoking status), 4) BP further adjusted for hypertensive medications.
Results
Two hundred and ten participants died during the follow-up period. Within the whole cohort, the univariate model indicated a positive association between all-cause mortality for supine SBP (HR: 1.030, 95% CI: 1.023-1.038, p<0.05) and standing SBP (HR: 1.023, 95% CI:1.016-1.031, p<0.05). Mortality was associated with the change in SBP (HR: 1.021, 95% CI: 1.007-1.036) in women only (p<0.05). Change in SBP was correlated with all-cause mortality after adjusting for risk factors only in women (HR: 1.025, 95% CI: 1.000-1.051; p≤0.05). Diastolic blood pressure (DBP) in the supine (HR: 1.030, 95% CI: 1.016-1.044), and standing (HR: 1.014, 95% CI: 1.001-1.028) positions in women, and change in DBP (HR: 1.013, 95% CI: 1.013-1.063) in men were correlated with all-cause mortality in the univariate model only (p<0.05, all).
Conclusion
These findings demonstrate the change from supine to standing SBP predicts risk for all-cause mortality in women, but not men after adjusting for risk factors. Assessing positional blood pressure may provide clinicians with additional diagnostic insight and predict all-cause mortality risk in women.

Change in Supine to Standing Systolic Blood Pressure (SBP) Predicts All-Cause Mortality in Women but not Men

Introduction
Hemodynamic gain index (HGI) is a marker of hemodynamic reserve inversely associated with major adverse cardiovascular events in patients undergoing exercise stress testing. HGI and traditional exercise markers, such as metabolic equivalents (METS), are derived from patient data from two to six decades ago. Modern patients have increased comorbidities and cardiac medication use which may affect the applicability of those exercise markers. HGI’s value in comparison to traditional exercise markers in a contemporary population is not well-characterized. 
Methods
This was a retrospective, single-center analysis of patients with exercise stress myocardial perfusion imaging from 2015-2017. Patients with >6 months follow-up and age >18 years were included. HGI was calculated with systolic blood pressure (SBP) and heart rate (HR): (SBPpeak x HRpeak – SBPrest x HRrest) / (SBPrest x HRrest). Other variables were calculated using prior literature: chronotropic incompetence (CI) = (HRpeak – HRrest) / (220 - age - HRrest) <0.8; impaired heart rate recovery (HRR) = HRpeak – HR1, min <12 or HRpeak – HR2, min <22; abnormal blood pressure response (ABPR) = Bruce protocol stage 2 SBP >210 (males), SBP >190 (females), diastolic BP >110, or SBP decrease compared to baseline; abnormal METS = METS <7. Cox proportional hazard analysis modeled subsequent death or nonfatal myocardial infarction (NFMI).
Results
The study included 1582 patients (mean age 62 years, 37% female, 16% non-white) with mean follow-up 4.8 years. Prevalence of coronary artery disease (CAD) and anti-hypertensive medication use was 32% and >50%, respectively. Exercise marker abnormality prevalence was: 24.4% impaired HGI (HGI <1.4), 32.7% CI, 24.2% HRR, 32.3% ABPR, 14.9% METS. Impaired HGI had odds ratio (OR) 1.97 (p<0.001) in multivariable logistic regression accounting for traditional risk factors (sex, tobacco use, diabetes mellitus, hypertension, chronic kidney disease, and CAD), and OR 2.15 (p<0.01) in multivariable modeling with the four other exercise markers. In Cox multivariable modeling, HGI (HR 1.75, p <0.001) outperformed CI (HR 1.63, p=0.001), HRR (HR 1.24, p=0.262), ABPR (HR 1.46, p=0.039), and METS (HR 1.30, p=0.163). Cox model assumptions were verified using Schoenfeld residuals. HGI models were superior to other marker models (likelihood ratio test p<0.01).
Conclusion
In a modern cohort with increased medication use and comorbidities, HGI outperforms established exercise markers in predicting death and NFMI. HGI can be easily calculated using vital signs and provides graded risk assessment beyond other markers. Greater application of this hemodynamic variable in exercise testing can augment ischemic heart disease prognostication.

Comparing the Prognostic Value of Hemodynamic Gain Index to Traditional Assessments of Exercise Hemodynamics in a Modern Cohort

Abstract Title: 

Consanguinity and Atrial Septal Defect: Genetic and Environmental Factors in Global Populations 

Background: 

Atrial septal defect (ASD) accounts for approximately 10 to 15 percent of congenital heart diseases, with a reported birth prevalence of approximately 1 to 2 per 1000 live births. This study aims to explore the relationship between consanguinity and ASD, addressing gaps in understanding both genetic and environmental factors. 

Methods: 

A search of PubMed articles (January 1950 - July 2024) using Medical Subject Headings (MeSH) terms 'congenital heart disease' and 'consanguinity', limited to English language articles, yielded 642 results. The focus was on articles that studied the relationship between consanguinity and ASD across various countries. 

Results: 

A Moroccan study found 3 heterozygous NKX2-5 variants in 9.4% of ASD patients, with 30.8% reporting consanguinity. In Northeast Iran, 85% of ASD patients had secundum ASD, and consanguinity significantly correlated with ASD type (P < 0.001), gender (P < 0.001), and age of onset (P = 0.003). Western Iraq exhibited notably higher consanguinity rates in congenital heart disease cases (78%) compared to controls (43.3%), with first-cousin consanguinity particularly elevated in cases (66.2%) versus controls (35.6%). In South India, consanguinity, including first cousin (44.68%) and uncle-niece marriages (46.81%), significantly increased the risk of ASD. 

Conclusion: 

These findings underscore a significant relationship between consanguinity and ASD prevalence, with consanguinity emerging as a substantial environmental risk factor alongside genetic predispositions such as NKX2-5 variants. The Moroccan cohort study suggests that consanguinity, coupled with a high incidence of maternal miscarriages and sudden sibling deaths, indicates a non-sporadic nature of ASD, potentially influenced by ethnicity. Studies in Western Iraq and South India show that consanguinity significantly increases the risk of ASD, highlighting the role of recessive gene segregation. The elevated prevalence of ASD among consanguineous marriages emphasizes the need for pre-marriage counseling to educate couples about the genetic risks associated with inbreeding. Social education campaigns could raise awareness about these risks and promote healthy family planning practices. Understanding the interplay between genetic and environmental factors is crucial for developing effective prevention and management strategies. Future research should prioritize whole-exome sequencing to identify causative genes of ASD within consanguineous communities.

Consanguinity and Atrial Septal Defect: Genetic and Environmental Factors in Global Populations

Background
Sex-specific research dealing with the impacts of the endocrine system and menopause on the cardiovascular health of women is essential. In this work, we assess the effects of hypothyroidism and menopause on physiologic metrics (i.e. weight, temperature), blood pressure, cardiac function (i.e. ejection fraction, cardiac output), and degree of hypertrophy (i.e. myocyte size, heart weight) in a female rodent model of heart failure. This study aims to harness the positive cardioprotective effects of thyroid hormones and estrogen to identify heart failure treatment strategies and improve the heart health of women.

Methods
We examine the difference in cardiac repair responses to exogenous administration of triiodothyronine (T3), 3,3’-diiodothyronine (3,3′-T2), and estrogen (E2) in hypothyroid, postmenopausal female rats that have surgically induced myocardial infarctions (MI) via permanent ligation of the Left Anterior Descending (LAD) artery. Hypothyroidism was induced via daily propylthiouracil (PTU) administration (1 mg/mL in their drinking water), and menopausal state induced surgically via ovariectomy (OVX). Rats were weighed daily, and blood pressure, thyroid hormone levels, and temperature were monitored weekly for 9 weeks. Echocardiograms and electrocardiograms were performed pre- and post-LAD ligation to confirm MI, establish exclusion criteria, and evaluate differences in cardiac function. Rat hearts and thyroids were harvested, weighed, and stained using H&E and Picrosirius Red to assess for hypertrophy. Serum was analyzed for T3, T4, and TSH using a Luminex Assay to determine the effects of exogeneous hormone replacement therapy on endogenous hormone levels.

Results
PTU administration resulted in significant reductions in rodent body weight and temperature as well as thyroid gland size. Blood pressure measurements showed a significant reduction in pulse in the hypothyroid rats. After MI, both euthyroid and hypothyroid rats experienced similar levels of decreased cardiac function. However, while T3 treatment resulted in a lower left ventricular ejection fraction (LVEF) % in euthyroid rats compared to saline and 3,3’-T2 treated rats, in hypothyroid rats it resulted in a higher LVEF%. Cardiac output was higher when hypothyroid rats were treated with T3 when compared to saline and 3,3’-T2 treatment.

Conclusion
We show that T3, in the euthyroid status has a detrimental effect, decreasing LVEF while in the hypothyroid status improves LVEF. Therefore, administration of thyroid hormones in hypothyroid individuals could be used productively for the treatment of heart failure, despite current contraindications. This study will evaluate if underlying estrogen hormone imbalances affect cardiac repair and better determine any confounding effects when administered with thyroid hormones.

Effects of Hypothyroidism and Menopause on Cardiac Repair in Female Rats Post-Myocardial Infarction

Background: Patients with atrial fibrillation (AF) are at a higher risk of stroke. For non-valvular AF (NVAF), direct oral anticoagulants (DOACs) are the preferred initial treatment for stroke prevention due to their lower risk of stroke, mortality, and intracranial hemorrhage compared to warfarin. The global prevalence of atrial fibrillation is increasing due to the aging population. However, many patients, especially elderly individuals with frailty and multiple comorbidities, find it challenging to adhere to DOAC therapy. Factors such as frailty, dementia, anemia, and chronic kidney disease play a significant role in the decision-making process for prescribing anticoagulants in older patients. Despite the benefits of DOACs, there are concerns about bleeding risk in specific patient subgroups, such as those with mechanical heart valves, thrombotic antiphospholipid syndrome, and advanced renal and liver disease.

Methods: We conducted a meta-analysis by searching PubMed, Scopus, and Cochrane Central for studies comparing factor XI/XIa inhibitors with DOACs in patients with NVAF. Our primary outcome was the occurrence of major or clinically relevant non-major bleeding (CRNM) according to the ISTH criteria. Statistical analysis was done using Review Manager. Heterogeneity was examined using I2 statistics.

Results: We evaluated data from two RCTs with 2042 NVAF patients. In AZALEA-TIMI 71, 1287 patients received abelacimab 150 mg (n = 427), abelacimab 90 mg (n = 425), or rivaroxaban 20 mg (n = 430). In PACIFIC-AF, 755 patients were assigned to asundexian 20 mg (n=249), asundexian 50 mg (n=254), or apixaban (n=250). The patients had an average CHA2DS2-VASc score of 4.45 (±1.15) and a mean age of 73.6 years (±8.5). Of the participants, 42.45% were female, 25% had preexisting chronic kidney disease, 13.85% had a history of prior ischemic stroke, and 8.6% had a history of prior bleeding. The primary endpoint, major or CRNM (HR 0.31; 95% CI 0.22-0.44; p < 0.00001; I2=0%), was significantly lower in patients treated with Factor XI therapeutics compared with Factor Xa inhibitors.

Conclusion: Patients assigned to either dose of Factor XI inhibitors asundexian or abelacimab exhibited significantly lower rates of bleeding compared to the DOACs. The inhibition of Factor XI appears to be a promising strategy for preventing abnormal blood clots and reducing the risk of bleeding in patients with atrial fibrillation. Further evaluation in a Phase 3 trial is needed.

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