United States

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 &gt;6 months follow-up and age &gt;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) &lt;0.8; impaired heart rate recovery (HRR) = HRpeak – HR1, min &lt;12 or HRpeak – HR2, min &lt;22; abnormal blood pressure response (ABPR) = Bruce protocol stage 2 SBP &gt;210 (males), SBP &gt;190 (females), diastolic BP &gt;110, or SBP decrease compared to baseline; abnormal METS = METS &lt;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 &gt;50%, respectively. Exercise marker abnormality prevalence was: 24.4% impaired HGI (HGI &lt;1.4), 32.7% CI, 24.2% HRR, 32.3% ABPR, 14.9% METS. Impaired HGI had odds ratio (OR) 1.97 (p&lt;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&lt;0.01) in multivariable modeling with the four other exercise markers. In Cox multivariable modeling, HGI (HR 1.75, p &lt;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&lt;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.

AMA Research Challenge 2024 

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

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.

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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.

Factor XI-directed therapeutics in balancing stroke prevention and bleeding risk in Atrial Fibrillation: A Meta-analysis

Background
It is unclear whether heart donor cause of death (CoD) influences recipient mortality and if cardiovascular risk varies by region. By analyzing the UNOS database, it can be determined if donor CoD impacts recipient post-transplant mortality and if regional differences influence cardiovascular health.

Methods
The United Network for Organ Sharing (UNOS) registry was queried for all adult heart transplant recipients and donors from 1987 to 2023 in Southern, Western, Northeastern, and Midwest states. Donors were grouped by CoD, including anoxia, gunshot wounds/trauma (GSW), intracranial bleed/stroke (IS/B), and other causes of death. Unadjusted and adjusted mortality was compared.

Results
Of the 56,901 patients included in this analysis, GSW donors accounted for the smallest number of donors (18.13%, p <0.001), the lowest number of female donors (11.38%, p <0.001), and the youngest patients (26.85 ± 9.54, p <0.001). IS/B donors had the highest donor age (40.26 ± 11.19, p <0.001) and the highest number of female donors (11.19%, p <0.001). Mortality at 30 days, 1 year, and 5 years varies significantly according to the CoD (p<0.001). Recipients of IS/B hearts had worse mortality rates 30 days, 1 year, and 5 years post-transplant (6.55%, 14.67%, and 30.04%). Recipients from GSW donors had the best mortality rates 30 days, 1 year, and 5 years following transplant (4.60%, 11.42%, and 26.44%). When adjusting for covariables and mortality by region compared to the Northeast, the South had the increased mortality (hazard ratio [HR] = 1.09, 95% confidence interval [CI] = 1.06-1.13, p <0.001) and the West had decreased mortality (HR = 0.93, 95% CI = 0.89-0.97, p <0.001). When comparing other donor CoD to GSW, IS/B, and anoxia donor CoD within each region, there were no significant differences in mortality rates.

Conclusion
This study looked at geographical differences in donor CoD and mortality rates. The mortality of heart transplant recipients varies according to the CoD of the donor, even when adjusted for different regions. No significant differences were observed when analyzing each region individually according to the donor CoD.

Impact of Donor Cause of Death and Geographic Location on Recipient Mortality Post Heart Transplant- a UNOS Database Review

Aims:

The use of intra-aortic balloon pumps (IABP) or percutaneous left ventricular assist devices (pLVAD) in patients with cardiogenic shock (CS) or high-risk percutaneous coronary interventions (PCI) is controversial due to limited data. This study aims to investigate the impact of these devices on hemodynamic and clinical outcomes in patients with high-risk PCI or CS.


Methods:

We systematically searched Embase, PubMed, and Scopus for randomized controlled trials (RCTs) and observational studies comparing pLVAD versus IABP or medical therapy in high-risk PCI or CS patients. The primary outcome was major adverse cardiovascular events (MACE). Secondary endpoints included in-hospital stroke and severe bleeding etc. Heterogeneity was assessed using I2 statistics, and a random-effects model was applied for outcomes with low and high heterogeneity.


Results:

This meta-analysis of 7 RCTs and 27 observational studies including 73,701 patients that compared pLVAD to IABP or medical therapy in high-risk PCI or CS patients over a follow-up of 1 month to 1 year. The mean age was 62.4 ± 13.2 years and 34.6 % of the patients were female. There was no significant difference between both groups for in-hospital or 30-day all-cause mortality (OR 1.15; 95% CI [0.90, 1.44]; p = 0.268), MACE (OR 0.97; 95% CI [0.66, 1.43]; P = 0.896), stroke in-hospital (OR 1.21; 95% CI [0.95, 1.54]; p = 0.116).
The incidence of kidney replacement therapy (KRT) (OR 1.73; 95% CI [1.46, 2.05]; p < 0.001), life-threatening bleeding (OR 2.37; 95% CI [1.84, 3.04]; p < 0.001), peripheral vascular access complications (OR 2.09; 95% CI [1.12, 3.88]; p = 0.020), acute kidney injury (AKI) (OR 1.50; 95% CI [1.39, 1.61]; p < 0.001) and hemolytic anemia (OR 6.17; 95% CI [2.00, 19.01]; p = 0.002) were significantly lowered in the pLVAD group than in the IABP or medical therapy group. 
Conversely, pLVAD significantly improved mean arterial pressure (MAP) (MD 11.87; 95% CI [6.72, 17.01]; p < 0.01) and cardiac index (MD 0.36; 95% CI [0.14, 0.57]; p < 0.01) . Furthermore, the use of pLVAD was associated with increased pulmonary capillary wedge pressure (PCWP) (MD -5.57; 95% CI [-10.14, -1.04]; p = 0.02).


Conclusion:

Our meta-analysis found no differences between pLVAD and IABP or medical therapy in in-hospital or 30-day, MACE and stroke in patients with high-risk PCI or CS. However, the use of pLVAD improved cardiac index, MAP as well as reduced the incidence of life-threatening bleeding. Adequately powered randomized controlled trials comparing pLVAD with IABP or medical therapy in patients with high-risk PCI or CS are warranted to define the optimal treatment strategy in patients with high-risk cohort.

Impact of Left Ventricular Assist Devices on Clinical and Hemodynamic Outcomes during Cardiogenic Shock or High-Risk Percutaneous Coronary Intervention

Background: Andersen-Tawil Syndrome (ATS) is an autosomal dominant channelopathy classified as long QT syndrome (LQTS) type 7, Characterized by periodic paralysis, ventricular ectopy/arrhythmia, and dysmorphic features. According to different authors, prolonged QTc is not always present, and thus it should be reclassified. However, no studies have found the correlation to life-threatening arrhythmias (LTAs) and prolong QTc. This study compared the likelihood of LTAs like VT and VF in ATS patients with prolonged QTc intervals against those with normal QTc.

Methods: To enable a meta-analysis, we searched literature reviews of reported cases or cohort studies with ATS between 1994 and 2024. Cases were selected if they presented a cardiologic affection. Prolong QTc interval was defined as QTc 440 msec in females and 460 msec for males. Each variable was calculated using the validated percentage. Numerical variables are expressed as mean and SD. Categorical variables are expressed as percentages. Student’s t-test was used for numerical variables. Categorical variables were analyzed using chi-square. Values of p <0.05 were considered statistically significant.

Results: 209 cardiologic-affected cases with ATS that provided information regarding the QTc interval were included. Of these, only 45.5% evidenced a prolonged QTc with a mean of 490  37 msec. ATS Probands were more likely to present a prolonged QTc than affected family members (51% vs. 29% respectively [p = 0.008]). Patients with prolonged QTc presented lower odds of a U wave than those with normal QTc (43% vs. 75%, respectively [p = 0.004]). Although there was no statistical significance when comparing LTAs in patients with prolonged QTc to normal QTc, LTAs were similar in both groups. VT episodes were more likely present with prolonged QTc than normal QTc (79% vs. 72%). However, episodes of sustained VT were more commonly present in cases with prolonged QTc than normal QTc (20% vs. 12%). Torsade de points and VF were more likely present in patients with a prolonged QTc interval than normal QTc (6% vs. 3% and 14% vs. 13%, respectively). Non-fatal cardiac arrest was slightly more common in cases with prolonged QTc than normal QTc (13% vs. 9%). Both prolonged and normal QTc had the same percentage of SCD (3%).

Conclusion: Although ATS has been classified as a long QT syndrome, prolongation is not always present. Patients with prolonged QTc demonstrated only a slightly increased percentage of developing LTAs compared to those with normal QTc.

Long QT type 7 (Andersen Tawil Syndrome): Is the QTc prolongation associated with higher odds of developing life-threatening arrhythmias or cardiac arrest?

Abstract Title
No Change in Endocarditis Rates in Patients with Congenital Heart Disease During the COVID-19 Pandemic
Background
Infective endocarditis (IE) is an infection of the endothelial layer of the heart with a yearly incidence of 10/100,000 in the general population, 25%-30% from healthcare related infections. Patients with congenital heart disease (CHD) have an increased risk for IE with a mortality rate of 19.4% at 6.7 years of follow-up. In 2025 there will be an estimated 355,000 adults aged 20-65 years of age with CHD. Poor dental hygiene and lack of preventive dental care are additional risk factors for developing IE.
In March 2020, the ADA Health Policy Institute reported 76% of dental offices were only seeing emergency cases and 19% were completely closed, and importantly for the adult CHD population, Medicaid dental coverage was limited or eliminated in many states.
We sought to investigate if the decreased access to dental care during the COVID-19 pandemic led to an increased burden of IE in the CHD population.
Methods
Retrospective review of a de-identified national administrative database (Vizient Clinical Data Base/Resource Manager) for hospitalized patients 2-80 years old with an ICD-10 code for any severity CHD between 10/1/2018 – 8/30/2022. Using the introduction of the ICD-10 code for COVID-19 (U07.1) in April 2020 to designate pre- and post-COVID time periods, two eras were defined: Era 1 (10/1/2018 – 3/31/2020) and Era 2 (4/1/2020 – 8/30/2022). Comparisons were made between endocarditis rates, demographics, length of stay, complication rates, in-hospital mortality and costs between Eras.
Results
There was a total of 264,126 admissions with CHD during the study period, 7,532 (2.9%) with CHD and IE. There was no difference in endocarditis rates between Eras (p = 0.478). The only differences identified were a slightly older age at admission in Era 2 (45 vs 47 years, p = 0.001) and higher costs in Era 2 ($48,952 vs 53,758, p = 0.017).
Conclusion
In this retrospective review of a large U.S. administrative database, we did not identify a significant change in IE hospitalization rates in CHD patients. While this finding is reassuring, it may not tell the complete picture yet.
IE is a relatively rare condition with an annual incidence of 11/10,000 in the CHD population and can take months for symptoms to develop. Given the relatively short period available for study, there may not have been sufficient time with limited access to dental care to effect oral health enough and increase IE rates. It will be important for future studies to continue to assess this question.

No Change in Endocarditis Rates in Patients with Congenital Heart disease During the COVID-19 Pandemic

Background: 
Acute coronary syndrome describes various conditions related to sudden, reduced blood flow to the heart. Some traditional risk factors for ACS include older age, diabetes (DM), hypertension (HTN), hyperlipidemia (HLD), smoking, and obesity. Rheumatoid arthritis (RA) is an autoimmune disease which is a novel risk factor for ACS. Therefore, to better understand the impact of this disease, we investigated whether RA is associated with increased mortality, readmission, and length of stay (LOS) in patients with ACS alongside traditional risk factors.

Methods: 
33,223 patients who were admitted with ACS to the West Florida division of a large health system from 1/1/2016 to 12/31/2023 were retrospectively included in the study. The association of risk factors, including RA, age, sex, Black ethnicity, other non-Caucasian ethnicities, current tobacco use, former tobacco use, alcohol use disorder, body mass index (BMI), HLD, and DM, with in-hospital mortality and 30-day readmission was evaluated via logistic regression and with LOS via negative binomial regression. 

Results:
- For RA:
The odds of in-hospital mortality was 0.779 times as likely (p-value .2252) and the odds of 30-day readmission was 0.948 times as likely (p-value .5671). RA resulted in a 1.034 factor increase in LOS (p-value .3369). 
- For traditional risk factors:
The odds of in-hospital mortality were 1.071 times as likely for every 1-year increase in age (p-value <.0001), 1.285 times as likely for current smokers (p-value 0.0020), 0.970 times as likely for every 1-point increase in BMI (p-value <.0001), 0.647 times as likely for patients with HLD (p-value <.0001), and 1.349 times as likely for patients with DM (p-value <.0001). 
Age, DM, and alcohol use disorder resulted in statistically significant increased 30-day readmission. 
Age, male sex, Black ethnicity, other non-Caucasian ethnicities, former tobacco use, current tobacco use, DM, and alcohol use disorder resulted in statistically significant increased LOS. 

Conclusion:
In terms of the discrete odds and incident rate ratios, RA was surprisingly associated with decreased in-hospital mortality and 30-day readmission in the setting of ACS despite an associated increased LOS. In terms of statistical significance, there was no difference in these outcomes in patients with RA versus patients without RA. Meanwhile, the traditional risk factors continued to show worse outcomes with statistical significance in the same patient population. Knowledge of this may prevent over-utilization of time, equipment, and resources when addressing hospitalized patients with RA presenting with ACS.

Rheumatoid Arthritis and Traditional Risk Factors on Outcomes in Acute Coronary Syndrome

Background
Right heart failure (RHF) is a complex syndrome commonly associated with serious cardiac and/or pulmonary disease and carries a high burden of morbidity and mortality. The burden of RHF versus left heart failure (LHF) and biventricular heart failure is not well-quantified and there is a lack of a direct comparison between these types of heart failure in patients’ data from a large clinical database. This study examines the prevalence of all-cause mortality and common comorbidities such as end-stage renal disease (ESRD) and cirrhosis in patients diagnosed with RHF versus LHF and other HF diagnoses.

Methods
Using the Epic COSMOS database, which integrates ICD-10 health information across over 200 health systems in the United States, we evaluated the proportion of death, cirrhosis, ESRD, and average length of hospitalization associated with RHF diagnoses versus other HF diagnoses, including LHF, from 1/1/2010-12/31/2023.

Results
From 577392 patients diagnosed with either RHF or LHF, we found 294233 diagnosed with RHF and 302222 diagnosed with LHF. 7027 were diagnosed with both.
RHF was associated with an average 38.7±0.2% death compared to 26.6±0.03% (p<0.0001) for that of other HF diagnoses and 31.1±0.2% (p<0.0001) for that of LHF diagnoses. The mean length of hospital stay was 7.5±0.03 days for RHF versus 6.7±0.01 days for other HF diagnoses. Furthermore, RHF patients were more likely to develop cirrhosis (p<0.0001) and ESRD (p<0.0001) than LHF patients after diagnosis.

Conclusion
Mortality associated with RHF is 12.3% greater than that of other HF diagnoses and 7.6% greater than that of LHF diagnoses. RHF seems to associate more with serious comorbidities such as ESRD and cirrhosis. Despite the increased mortality and morbidities associated with RHF, the length of hospitalization was not clinically different between the two groups. Since our data shows that RHF indicates a poor prognosis, greater emphasis should be placed on early diagnosis and management of RHF. Further studies are required to explore the pathophysiology of RHF and improve therapeutic approaches.

Right Heart Failure Linked to Worse Outcomes Than Left Heart Failure and Other Heart Failure

Background
Atrial fibrillation (AF) affects 38 million individuals worldwide and is responsible for $26 billion in healthcare costs in the U.S. alone, with 75% of costs attributed to hospitalizations. Early rhythm control improves cardiovascular outcomes in AF and is a cornerstone of treatment. Class III antiarrhythmic drugs (AADs) (e.g., dofetilide, sotalol) typically require inpatient initiation due to the risk of QT prolongation and torsades de pointes (TdP). This limits access and increases healthcare costs, with a single 3-day hospitalization for AAD initiation costing approximately $13,400. This burden disproportionately affects underserved populations, including minorities and rural populations, who may have limited access to appropriate healthcare facilities. We hypothesized that a novel machine learning (ML) algorithm paired with the SafeBeat Rx technology could enable safe outpatient AAD initiation, potentially improving access to care and reducing costs.
Methods
We developed CNN-BiLSTN based ML-model to automate ECG analysis and QTc measurement to drive AAD dosing recommendations. The model was trained on approximately 9M hand-annotated ECG heartbeats, utilizing data augmentation (e.g. noise) and k-fold cross validation (k=5). We then conducted a prospective study of patients admitted for in-patient dofetilide or sotalol initiation. Parallel to standard-of-care drug dosing, based on physician measured QTc on 12-lead ECG at baseline and 2 hours after each dose, patients were instructed to simultaneously record a mECG device (KardiaMobile 6L; AliveCor) which was transmitted to the software application. Software performance was evaluated by comparing software-annotated, physician adjudicated mECG QTc to blinded physician-measured 12-lead ECG QTc.
Results
A total of 50 patients (mean age 67 + 11 years, 64% male, 64% caucasian, 22% Asian/Pacific Islander, 8% Hispanic, mean baseline creatinine clearance 85.5 + 33.0mL/min, mean baseline QTc 417.7 + 30.1ms) underwent AAD initiation (44 dofetilide, 6 sotalol). The ML-based QTc measurement algorithm was used to analyze 314 mECGs that were used to guide 264 AAD doses. The ML- and physician-prescribed AAD dosing were congruent or more conservative in 245/264 (92.8%).
Conclusion
Overall, the software-recommended AAD drug dosing utilizing the ML QTc measurement was in high agreement with cardiologist-determined AAD drug dosing. These data demonstrate this software platform's potential to match clinician decisions for AAD dosing, offering the ability to support streamlined AAD titration regardless of patient setting. This approach shows promise for enabling safe outpatient initiation of AADs, potentially improving access to antiarrhythmic treatment and reducing healthcare costs.

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