bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4143258: Sex Differences in Health Status Outcomes: Analysis of the ISCHEMIA Randomized Clinical Trial
Authors: Grodzinsky Anna , Cho Yoon Joo , Jones Philip , Shaw Leslee , Bairey Merz C Noel , Boden William , Stone Gregg , Mark Daniel , Spertus John , Maron David , Hochman Judith , Reynolds Harmony
Published: November 2024

Background:
Despite a lesser extent and severity of coronary artery disease (CAD), women had a higher burden of angina than men in the ISCHEMIA trial, suggesting that other factors may explain symptom severity in women. We aim to describe demographic and clinical characteristics, as well as differences in care patterns, associated with health status differences in women, as compared with men, in the conservative and invasive treatment groups of the ISCHEMIA trial.

Methods:
The ISCHEMIA trial randomized participants with moderate or severe ischemia to a routine invasive strategy of cardiac catheterization with complete revascularization plus guideline-directed medical therapy (GDMT), or an initial conservative strategy of GDMT alone with catheterization reserved for GDMT failure. Health status was a key secondary outcome. Using linear regression models we compared raw and adjusted Seattle Angina Questionnaire (SAQ) scores in women and men at baseline and at 1 year, stratified by randomized treatment strategy. Within the invasive strategy, sex differences were adjusted for completeness of revascularization among those with ≥1 coronary stenosis ≥70%.

Results:
Of 4,617 ISCHEMIA participants with valid SAQ data, women had lower (worse) baseline SAQ summary scores (SS) throughout follow up (Figure) after adjustment for demographics and clinical characteristics, including severity of CAD (difference 5.4 points, 95% CI 4.0-6.7). Women had lower SAQ SS after adjustment for post-randomization treatment (i.e., medical therapy, achievement of risk factor goals and, in the invasive strategy, complete revascularization), 2.4 points lower (95% CI 0.7-4.1) in the conservative group (Figure), and 1.9 points lower than in men (95% CI 0.1-3.7) in the invasive group. Findings were similar for all SAQ subscales.

Conclusions:
Women with chronic coronary disease in ISCHEMIA had worse health status than men at baseline and 1 year later, which was not explained by demographic or clinical characteristics, intensity of medical therapy, or completeness of revascularization.
Abstract 4143270: PREDICTIVE MODELS AID PHYSICIAN PROGNOSTICATION: A SECONDARY ANALYSIS EVALUATING INTEGRATED MODEL AND PHYSICIAN PROGNOSTIC ESTIMATES IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION
Authors: Alba Ana , Buchan Tayler , Mueller Brigitte , Fan Steve , Poon Stephanie , Mak Susanna , Toma Mustafa , Zieroth Shelley , Anderson Kim , Porepa Liane , Demers Catherine , Chih Sharon , Giannetti Nadia , Rac Valeria , Ross Heather , Guyatt Gordon
Published: November 2024

Background:
In recent studies from a multicenter Canadian cohort of outpatients with heart failure (HF), we found that model predictions were significantly more accurate than HF cardiologists. In this study, trying to mimic practice, we evaluated the additional predictive value and clinical impact of model predictions to refine physician estimated risk of 1-year mortality by combining model and physician estimates.

Methods:
We included consented consecutive HF outpatients (LVEF <40%) followed at 11 HF clinics in Canada. HF cardiologists estimated patient 1-year mortality using their clinical judgment. We calculated model predicted mortality using the Seattle HF Model (SHFM). We followed patients for at least a year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using random forest survival model and cross-validation, we compared the performance SHFM and the HF cardiologist alone, and the integrated HF cardiologist and the SHFM predictions by evaluating model discrimination (c-statistic), calibration (observed vs predicted event rate), risk reclassification and clinical net benefit analyses.

Results:
Among 1,643 HF patients, 1-year event rate was 9% (95%CI 8%-11%). The SHFM had the adequate discrimination (c-statistic 0.76) and excellent calibration while cardiologists showed adequate discrimination (c-statistic 0.75) and poor calibration with significant risk overestimation (
Figure 1
). When the SHFM estimates were added physician predictions, discrimination significantly improved (0.82, 95%CI 0.78-0.86) with excellent calibration. By risk reclassification analysis, among patients with events, HF cardiologist better reclassified 44% than the SHFM or the integrated model. Among patients without event, however, HF cardiologists worse risk-classified 52% in comparison to SHFM and 71% to the integrated model. By net clinical benefit analysis (
Figure 2
), when the decision to treat involves patients with 1-year mortality of >5%, SHFM predictions would lead to higher benefit than guiding care by physician judgement. Integrating model and HF cardiologist predictions led to minimally increased benefit in comparison to SHFM alone.

Conclusions:
Integrating prediction from the SHFM to physician judgment or using the SHFM alone showed superior accuracy than HF cardiologist predictions, proving that model-informed care may provide more accurate prognostic information to tailor clinical decision making.
Abstract 4144501: Effect of the Cardiac Myosin Activator Omecamtiv Mecarbil on Risk of Ventricular Arrhythmias in Heart Failure with Reduced Ejection Fraction: the GALACTIC-HF Trial
Authors: Foa' Alberto , Vaduganathan Muthiah , Claggett Brian , Mani Govini , Diaz Rafael , Malik Fady , Heitner Stephen , Felker Gary , Metra Marco , McMurray John , Teerlink John , Solomon Scott
Published: November 2024

Introduction:
The selective cardiac myosin activator, omecamtiv mecarbil (OM), has been shown to benefit individuals with HFrEF but the clinical experience of cardiac myosin activators and incidence of ventricular arrhythmias (VA) is limited. We investigated the prognostic role of VA and the associations between OM, VA occurrence, and outcomes in the GALACTIC-HF trial.

Methods:
GALACTIC-HF was a placebo-controlled trial testing the efficacy and safety of OM in participants with symptomatic chronic HF and LVEF≤35%. VA were captured based on safety adverse event reporting. Severe HF was defined according to the ESC-HFA criteria. Poisson regression models using restricted cubic splines model were used to assess the association between baseline LVEF and incidence rates of VA. Associations between incident VA and subsequent clinical outcomes were evaluated using time-updated Cox proportional hazard models.

Results:
Over a median follow-up of 21.8 months, 594 out of the 8,232 individuals randomized in the GALACTIC-HF trial experienced VA, with no statistically significant differences between study arms. Individuals with lower LVEF values were at greater risk of incident VA (per 10% decline: HR 1.37; 95% CI 1.21-1.55; p<0.001) with no significant differences between study arms (
Figure, panel A
). Following VA occurrence, participants were at higher risk of the primary endpoint of CV death or HF events (adj HR 1.67; 95% CI 1.42-1.97; p<0.001) and all-cause mortality (adj HR 2.07; 95% CI 1.77-2.42; p<0.001). The treatment effects of OM on clinical outcomes were consistent in patients not experiencing VA and after VA events. Among the 2,258 participants with severe HF, OM did not affect the risk of VA (adj HR 0.95; 95% CI 0.70-1.29) and this was consistent across the range of LVEF;
Figure,
panel B
.

Conclusions:
The occurrence of VA among patients with HFrEF is associated with a substantially higher risk of subsequent fatal and non-fatal events. OM did not increase the risk of VA and the beneficial treatment effects were maintained irrespective of VA occurrence. These findings reinforce the safety of OM use among individuals with HFrEF who are at risk of arrhythmic events.
Abstract 4144502:
Comparing Readmission Rates and Exercise Capacity Following Left Ventricular Assistive Device Placement With and Without Post-Operative Inpatient Rehabilitation
Authors: Cuenant Lauren , Raja Junaid , Tiozzo Eduard , Pontee Nicole
Published: November 2024

Introduction:
Patients with heart failure may undergo mechanical assistive device placement as a bridge to heart transplantation or for destination therapy. Thereafter, patients may be discharged home or admitted to inpatient rehabilitation.

Research Question:
We hypothesized that within 8 months, patients admitted to inpatient rehabilitation (IR) would have fewer readmissions and greater exercise capacity compared to patients discharged home following left ventricular assistive device (LVAD) placement.

Aim:
The readmission rates and exercise capacity of patients admitted to (IR) were compared to those discharged home within 8 months of (LVAD) placement.

Methods:
Readmission rates, impairment percentages (IP) (determined by Activity Measure for Post-Acute Care scores) and walking distance after (LVAD) placement between March 1
st
, 2020 to November 30
th
, 2022 were collected via retrospective chart review at Jackson Memorial Hospital.

Adults with heart failure and heart assistive device (ICD10 code Z95.811), discharged home or admitted to the Christine E. Lynn Rehabilitation Center for at least 7 consecutive days within 8 months were included. Patients who were noncompliant, expired, transferred, or unable to ambulate were excluded. 24 patients were admitted to rehab, and 16 were discharged home. Statistical significance was denoted at the 0.05 level using the Mann-Whitney U Test.

Results:
There was a higher proportion of females in the rehab group (45.8%) and males in the no rehab group (93.8%) (p=0.02). The groups were otherwise comparable.

Average (IP) at hospital discharge was higher for the rehab group (51.79%, SD 17.65) compared to the no rehab group (14.20%, SD 18.93) (p<.001). Average post-(LVAD) walking distance (feet) at hospital discharge was higher for the no rehab group (305, SD 206.72) compared to the rehab group (127.73, SD 132.11) (p=0.005). Within 8 months, there was no significant difference between groups.

Average readmissions were higher for the no rehab group (1.375, SD 0.957) compared to the rehab group (0.958, SD 1.49) (p= 0.059), but was not statistically significant.

Conclusions:
Patients with greater (IP) and shorter walking distances were admitted to rehab and became functionally comparable to the no rehab group by 8 months. Though readmission rates were lower for the rehab group, this was not statistically significant. Additional studies are warranted to evaluate the impact of (IR) following (LVAD) placement.
Abstract 4144503: Association of Granular Sleep Health Metrics with Arterial Stiffness in the Community
Authors: Alhassan Hassan , Jha Mawra , Vasan Ramachandran , Mitchell Gary , Thomas Robert , Tsao Connie
Published: November 2024

Introduction:
Poor sleep is a risk factor for cardiovascular disease and all-cause mortality; however, the mechanisms underlying this relationship remain poorly understood. Since sleep health is a complex construct extending beyond mere sleep duration, we aimed to examine the relationship between granular sleep health indicators and arterial stiffness.

Methods:
We analyzed Framingham Offspring cohort (Exam 9) and OMNI cohort 1 (Exam 4) participants with sleep study and applanation tonometry data (n= 847, 56.6% females). Participants wore an M1 device to obtain ECG-derived sleep spectrograms to assess sleep quality and the Nonin WristOx device for oximetry data over two consecutive nights. Sleep variables of interest included total sleep time, duration of stable and unstable NREM, duration of elevated low-frequency coupling (e-LFC), and duration and number of nocturnal hypoxia events. Measures of aortic stiffness and pressure pulsatility included carotid-femoral pulse wave velocity (PWV), and central pulse pressure (CPP).

Results:
Characteristics of the sample are presented in Table 1. Several sleep measures were associated with PWV in univariable analysis, but significance attenuated after age/sex adjustment (Table 2). After adjusting for cardiovascular risk factors and sociodemographics, duration of e-LFCnb remained associated with CPP (β = 0.036, p = 0.02)

Conclusion:
Sleep measures associated with aortic stiffness are closely tied to age and sex. Longer duration of e-LFCnb, a hallmark of carotid body-driven elevated sympathetic tone and periodic breathing, is associated with greater pressure pulsatility. Longitudinal studies are needed to fully elucidate the role of e-LFCnb in vascular health
Abstract 4144508: Efficacy and Safety of Intravenous Hydralazine vs Intravenous Labetalol in Management of Gestational Hypertension: A Meta-analysis of Randomized Controlled Trials
Authors: Upreti Prakash , Basit Jawad , Nasir Muhammad Moiz , Ahmed Mushood , Fatima Maurish , Goyal Aman , Hamza Mohammad , Ashraf Saher , Alraies M Chadi
Published: November 2024

Background:
Hypertension in pregnancy affects around 15% of all pregnant women and is one of the leading causes of maternal and fetal, mortality and morbidity. Hydralazine and labetalol are administered intravenously to control hypertension in pregnant women. However, data regarding their comparative efficacy and safety is limited. Considering the paucity of data, we conducted a systematic review and meta-analysis to pool all the studies published on this subject and provide robust evidence.

Methods:
We followed PRISMA guidelines for conducting this systematic review and meta-analysis. Two investigators searched PubMed/MEDLINE, Scopus, the Cochrane Library, and Google Scholar from inception until May 2024. The randomized controlled trials (RCTs) which compared the effects of intravenous labetalol versus hydralazine in pregnant women with hypertensive disorder of pregnancy were included in our pooled analysis. A random-effects model was used to calculate the weighted mean differences (MD) for continuous outcomes and odds ratio (OR) for the discrete outcomes along with the corresponding 95% confidence intervals (CIs). We considered a p-value of less than 0.05 statistically significant in all cases.

Results:
A total of 8 RCTs with total population of 1138 patients were pooled. The pooled analysis showed that the final systolic blood pressure (MD = -4.74, 95% CI: -12.09 to 2.62, p = 0.21) and diastolic pressure (MD = -0.86, 95% CI: -9.22 to 7.49, p = 0.84) remained comparable. The incidence of maternal hypotension (OR = 0.13, 95% CI: 0.06 to 0.29, p<0.001) was significantly lower with labetalol administration compared to hydralazine. However, we found no statistically significant difference between two groups for persistent hypertension (OR = 0.86, 95% CI: 0.37 to 1.97, p = 0.72), neonatal death (OR = 2.97, 95% CI: 0.58 to 15.25, p = 0.19), stillbirth (OR = 0.73, 95% CI: 0.25 to 2.17, p = 0.57), fetal arrhythmia (OR = 0.56, 95% CI: 0.30 to 1.07, p = 0.08), APGAR score < 7 at 5 min (OR = 2.44, 95% CI: 0.69 to 8.65, p = 0.17), cesarean section (OR = 0.97, 95% CI: 0.53 to 1.80, p = 0.93), and the number of mean doses required for successful blood pressure control (MD = -0.37, 95% CI: -1.07 to 0.34, p = 0.31).

Conclusion:
Intravenous labetalol and hydralazine have similar efficacy and safety profiles for blood pressure control in pregnant women. However, the risk of maternal hypotension is significantly lower with labetalol administration as compared to hydralazine.
Abstract 4144514: Human Immunodeficiency Virus Associated Cardiomyopathy- A Rare Cause of Heart Failure With Reduced Ejection Fraction in Era of Highly Active Antiretroviral Therapy
Authors: Sabri Muhammad , Janga Chaitra , Riaz Faiza , Nugooru Sudeep , Haas Donald
Published: November 2024

Introduction:
Human Immunodeficiency Virus Associated Cardiomyopathy (HIVAC) is characterized by left ventricular (LV) systolic or diastolic dysfunction with or without LV dilatation and heart failure symptoms. The introduction of antiretroviral therapy (ART) has changed the fulminant systolic heart failure presentation of HIV myocarditis to diastolic heart failure. We present a unique case of dilated cardiomyopathy in a young patient without advanced HIV illness which has rarely been documented in the literature. This is a rare presentation of HIVAC in the post-ART era.

Case Report:
A 32-year-old male with a past medical history (PMH) of the human immunodeficiency virus (HIV) presented with complaints of new onset worsening shortness of breath and lower extremity edema for four weeks. He was diagnosed with HIV seven years ago and was not compliant with ART. Laboratory testing showed a cluster of differentiation 4 (CD4) 823 and HIV load 2550. Myocarditis was ruled out by normal troponin levels and no new changes on the electrocardiogram (ECG). Transthoracic echocardiogram (TTE) showed dilated left ventricle (LV), LV global hypokinesis, LV ejection fraction (LVEF) 10-15%, dilated right ventricle, biatrial dilation, moderate to severe mitral regurgitation, severe tricuspid regurgitation, pulmonary artery (PA) systolic pressure 73 mmHg and no pericardial effusion. Coronary angiography was negative for coronary artery disease (CAD). The patient was started on carvedilol and outpatient evaluation for a left ventricular assistance device.

Discussion:
Systolic dysfunction in patients with HIVAC carried a poor prognosis in the pre-ART era and was common in patients with elevated c-reactive protein (CRP), tobacco use, and previous myocardial infarction (MI). After the advent of ART, systolic dysfunction is rare and replaced by diastolic cardiomyopathy in the setting of ART use. Diagnosis is usually by excluding other etiologies and biopsy is not necessarily required. Management is usually guideline-directed medical therapy (i.e. beta blocker, renin-angiotensin-aldosterone antagonists, sodium-glucose cotransporter-2) and device-based therapy but there is still data lacking to assess its benefit.
Abstract 4144520: Glucagon-like Peptide-1 Receptor Agonists for the Primary Prevention of Major Adverse Cardiac Events in Drug-naïve Type 2 Diabetes: A Propensity-score Analysis
Authors: Chi Kuan Yu , Lee Pei Lun , Osabutey Anita , Borkowski Pawel , Song Junmin , Akman Zafer , Romero Acero Laura , Maliha Maisha , Satish Vikyath , Chang Yu , Nanna, MD, FACC Michele , Nanna Michael
Published: November 2024

Background:
The effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RA) as a first-line agent for the primary prevention of major adverse cardiac events (MACE) in obese patients with diabetes mellitus (DM) is unknown.

Research Question:
Does initial treatment with GLP-1 RA in obese drug-naïve patients with type 2 DM prevent future MACE?

Aims:
To examine the association between GLP-1 RA treatment and the primary prevention of MACE in drug-naïve type 2 DM patients with obesity.

Methods:
A retrospective propensity score-matched (PSM) analysis was conducted using the TriNetX Global database. We implemented a new-user design, including adult overweight/obese patients with drug-naive type 2 DM between January 1
st
, 2019 and May 1
st
, 2023. Patients with prior heart failure (HF), myocardial infarction (MI), coronary revascularization, stroke, or cardiac arrest were excluded. We compared those starting GLP-1 RA versus starting non GLP-1 RA. Medication starting window spans from the first diagnosis to 3 months afterwards. Patients with insulin were excluded if they had any emergency or inpatient encounters during this window. The primary outcome was incident MACE, defined as any death, decompensated HF, MI, cardiac arrest, or ventricular tachycardia/fibrillation, within 5 years of initial drug dispense. Secondary outcomes were individual MACE. Gastrointestinal bleeding was set as a falsification endpoint.

Results:
Of 1,245,340 patients with A1c <10% and 293,072 patients with A1c ≥10%, 7,483 and 1,563 patients started on GLP-1 RA as a single agent and part of a combined approach, respectively. After PSM, baseline covariates were balanced between the two treatment groups and no significant differences were observed in the falsification endpoint by treatment arm
(Figure)
. Compared with non-GLP-1 RA, with the exception of sodium-glucose cotransporter-2 (SGLT2i), starting a GLP-1 RA first was associated with a significant reduction in MACCE, primarily driven by reductions in decompensated HF
(Figure)
.

Conclusions:
Initiation of a GLP-1 RA as the first agent for obese patients with drug-naïve type 2 DM was associated with a significant reduction in MACE compared to all other diabetes medications, with the exception of SGLT2i.
Abstract 4144526: A Case Presentation of Severe Left Ventricular Dysfunction from Focal Myocarditis due to Immune Checkpoint Inhibitor
Authors: Patel Romil , Hussain Kifah , Gordon Robert
Published: November 2024

Introduction:
Immune checkpoint inhibitors (ICI), such as pembrolizumab, are an effective immunotherapy for several malignancies, however, have been associated with adverse events including myocarditis and accelerated atherosclerosis. ICI myocarditis is associated with a mortality rate of up to 33%. This case reports a patient on pembrolizumab with an atypical presentation.

Case presentation:
A 75-year-old female with a past medical history significant for lung cancer on pembrolizumab and myasthenia gravis presented to the hospital with dyspnea and mild, intermittent exertional chest discomfort. She denied nausea, radiation of pain, diplopia, weakness in extremities, or dysphagia. Workup revealed a leucocyte count of 13,500 cells/uL, pro-brain natriuretic peptide of 13,458 pg/mL, troponin of 26 ng/L, and a normal erythrocyte sedimentation rate and C reactive protein. A chest computed tomography was performed that showed mild bilateral pleural effusion and no pulmonary embolism. A nuclear stress test showed no evidence of ischemia but showed a severely reduced left ventricular ejection fraction (LVEF) at 29%. An echocardiogram confirmed that the ejection fraction was reduced at 23% (baseline LVEF was 60% from 1 year ago). Cardiac MRI revealed a mildly increased regional T2 signal in the anterolateral wall, mildly elevated extracellular volume fraction, and no late gadolinium enhancement. With ongoing clinical suspicion despite equivocal findings on cardiac MRI, an endomyocardial biopsy was done that revealed a single small aggregate of lymphocytes present in 1 of 6 tissue samples. Ultimately, with the single site of aggregated lymphocytes on biopsy, a diagnosis of ICI myocarditis was determined, and the patient was started on high-dose intravenous glucocorticoids as well as bisoprolol, empagliflozin, spironolactone, and Entresto for heart failure management as she was able to tolerate.

Discussion:
Myocarditis due to pembrolizumab is a rare, but potentially lethal adverse effect. Patients typically have abnormal electrocardiograms and elevated cardiac biomarkers. Cardiac MRIs have sensitivity and specificity of 68% and 91% respectively for diagnosis, and the gold standard is endomyocardial biopsy however, it is limited due to sampling error. Our patient had an unusual presentation, but with both imaging and biopsy, we found a case of focal myocarditis with severe left ventricular dysfunction, which typically is seen with fulminant myocarditis.
Abstract 4144528: The Polygenic Mechanisms of Dilated Cardiomyopathy Contribute to The Development of Tachycardia-Associated Cardiomyopathy in Patients With Atrial Tachyarrhythmias
Authors: Safabakhsh Sina , Jordà Paloma , Grondin Steffany , Parker Jeremy , Fazeli Amir , Castillo Ismael , Laksman Zachary , Tardif Jean-Claude , Tadros Rafik , Raymond-Paquin Alexandre
Published: November 2024

Background

Longstanding tachycardia can lead to reversible left ventricular (LV) systolic dysfunction called tachycardia-associated cardiomyopathy (TAC). It is unknown if there is a genetic predisposition to the development of TAC or whether there is overlap between the genetic pathways of TAC and dilated cardiomyopathy (DCM).

Research Questions

Is there a genetic predisposition towards the development of TAC in individuals with arrhythmia? If so, do these genetic pathways overlap with those of DCM?

Methods/Approach

The study is a single-center case control study performed at the Montreal Heart Institute (MHI). Inclusion criteria for TAC cases are shown in Table 1. All cases underwent array genotyping and exome sequencing. Previously genotyped controls with arrhythmia but no documented LV dysfunction were included from the MHI Biobank. Following imputation using the TOPMed imputation server, a polygenic score for DCM (PGS
DCM
; PGS000666) was calculated for cases and controls. The rate of (likely) pathogenic variants in known cardiomyopathy genes was reported in cases.

Results/Data (descriptive and inferential statistics)

The study included 107 cases and 878 controls. Case characteristics are shown in Table 1. The average PGS
DCM
for cases was significantly higher than that of controls (p-value <10
-10
; Figure 1). Logistic regression with correction for age, sex, and ancestry (principal components) showed a strong association of PGS
DCM
with TAC (OR 1.99, 95% CI 1.54-2.58; p-value <10
-6
). Notably, among patients with atrial tachyarrhythmias, those with a PGS
DCM
above the 95
th
percentile had a 3.53-fold increased risk of TAC (p-value 4.5
-4
). Exome sequencing in TAC cases identified only 2/107 (2%) carriers of (likely) pathogenic variants (in cardiomyopathy genes
TNNT2
and
MYH7
).

Conclusions

Pathogenic variants account for a small minority of TAC cases. In contrast, a significant association between PGS
DCM
and TAC is suggestive of a shared polygenic pathway between TAC and DCM.
Abstract 4144542: In-Hospital Outcomes of Open Mitral Valve Repair or Replacement versus Percutaneous Mitral Valve Repair or Replacement in patients with Prior Mediastinal Radiation: Insight from The National Inpatient Database (2015-2020)
Authors: Osama Muhammad , Naeem Nauman , ahmed asmaa , Ahmad Muhammad , Rehman Saif ur , Sharif Muhammad Hammad , Balmer-Swain Mallory
Published: November 2024

Background:
Radiation associated heart disease has a wide spectrum of manifestations including pericardial disease, coronary artery disease, and valvular heart disease. Mitral valve regurgitation is the second most common valvular dysfunction in patients with prior mediastinal radiation.

Research Question:
What are the outcomes of percutaneous or transcatheter mitral valve replacement/repair (T-MVR) versus surgical mitral valve replacement/repair (S-MVR) in patients with prior mediastinal radiation.

Methods:
The National Inpatient Sample (NIS) was analyzed from 2015-2020 to identify patients with mediastinal tumors and prior exposure to radiation therapy undergoing mitral valve repair/replacement. We subclassified the data into hospitalizations for S-MVR and T-MVR. Baseline characteristics were compared between the two groups and multivariate logistic regression was used to analyze hospitalization outcomes.

Results:
A total of 1725 patients with prior mediastinal radiation were hospitalized for MVR; 1110 (64.3%) patients underwent S-MVR and 615 (35.6%) patients underwent T-MVR. On a multivariable analysis, the odds of MACCE [aOR: 2.21; 95 % CI: (1.87-4.01); p <0.001)], and in-hospital mortality [aOR: 5.6; 95% CI (2.06-7.35); p=0.008] were higher in patients undergoing S-MVR compared to those undergoing T-MVR. Additionally, patients undergoing S-MVR had higher odds of periprocedural complications including cardiogenic shock [aOR: 7.4; 95% CI: (3.75 -9.20); p <0.001], major bleeding [aOR: 2.9; 95% CI: (1.26-7.09); p=0.01], AKI [aOR: 3.4; 95% CI: (1.33-5.23); p <0.001], stroke [aOR: 5.01; 95% CI: (1.51-6.57); p=0.008], and MCS utilization [aOR: 3.05; 95% CI: (1.31-7.13); p=0.009] compared to the T-MVR cohort.

Conclusion:
Compared to T-MVR, S-MVR was associated with higher odds of MACCE, in-hospital mortality and periprocedural complications suggesting that T-MVR might be a safer option for MVR among patients with prior mediastinal radiation.
Abstract 4144548: High Morbidity and Mortality in Adults With Turner Syndrome and Aortic Dilation: A Retrospective Cohort Study from the Healthy Heart Project
Authors: Kathiresan Rakesh , Vj Nikhil , Rios Deborah , Quezada Emilio , Silberbach Michael , Prakash Siddharth
Published: November 2024

Introduction:
Turner syndrome (TS) is caused by the partial or complete absence of one sex chromosome and affects 1 in 2500 liveborn infants. Hypertension, bicuspid aortic valve (BAV), and thoracic aortic aneurysms (TAAs) are more prevalent in TS compared to the general population and predispose to aortic dissections, which may occur in young adults with TS. We hypothesize that adults with TS who have TAAs experience a high rate of adverse cardiovascular outcomes.

Methods:
Adults with TS who had Healthy Heart Project (HHP) echocardiograms at national conferences between 2003 and 2023 were contacted for enrollment in descending order of the aortic size index (ASI, cm/m
2
), defined as the ratio of the maximum ascending aortic diameter to body surface area. After informed consent, clinical characteristics and outcomes (as numbers of participants or median and interquartile range) were abstracted from questionnaires and medical records.

Results:
Sixty-four of 704 total HHP participants were contacted and 19 (with 10 of the 20 highest ASI values) were enrolled with complete data. The baseline ASI was 2.19 (0.48), compared to 1.51 (0.36) for all other HHP participants. The median age was 59 (13) years. The most prevalent characteristics were 45,X (10) or 45,X/46,XX (6) karyotypes; BAV (9), coarctation (4), or no congenital lesions (6); and hypertension (12). A mean of 10 serial aortic images were available for each participant over a follow up period of 14 (9.8) years. The median increase in aortic diameter was 0.09 (0.29) mm/yr at the sinuses of Valsalva and 0.26 (0.44) mm/yr at the ascending aorta. Seven participants underwent aortic operations due to enlarging TAAs when the median ascending diameter was 3.83 (0.67) cm (ASI 2.58 (0.11) cm/m
2
). In 3 cases, operations were urgent due to cardiovascular symptoms or rapid aortic dilation, but there were no acute aortic dissections. The median time between the index image and subsequent repair was 3.5 (7.0) years. Three HHP participants with the 8th, 15th, and 42nd largest ASI values died prior to follow up. One death was caused by complications after surgical aortic valve replacement at age 20.

Conclusions:
In a cohort of adults with TS and TAAs, 40% (7/19) developed progressive aortic enlargement requiring aortic repairs and there were 3 deaths. These observations underscore the importance of lifelong surveillance and timely intervention to prevent deaths due to cardiovascular disease in TS.
Abstract 4144559: Sex Differences in Vascular Remodeling in Pulmonary Hypertension are mediated by Endothelin-2
Authors: Medzikovic Lejla , Cunningham Christine , li min , Aryan Laila , Sun Wasila , Dehghanitafti ateyeh , Ruffenach Gregoire , Hong Jason , Eghbali Mansoureh
Published: November 2024

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial vascular remodelingleading to increased pulmonary artery pressure causing right ventricular hypertrophy, failure anddeath. The incidence of PAH is much higher in female patients, indicating that males may have aprotective factor that could help elucidate the pathogenesis of PAH. We have recently demonstratedthat the Y chromosome gene UTY protects against PH development in mice, however the fulldownstream mechanisms remains unknown. By integrating RNA-Seq on whole lung tissues fromUty-KO and WT male mice with a publically available male and female PAH lung microarraydataset, we found increased expression of Endothelin 2 (ET-2) in the lungs of Uty-KO compared toWT mice with PH as well as in the lungs of female patients compared to males with PAH. The roleof ET-1 is known in PAH, and Endothelin receptor antagonists are a common PAH therapy to whichfemale patients are more responsive. However, ET-2 has yet to be investigated in this context. Wevalidated that ET-2 expression is significantly increased in lung tissue from PAH female patientscompared to males. Plasma ET-2 concentration is also significantly higher in PAH patients versuscontrols. Interestingly, plasma ET-2 negatively correlates with pulmonary vascular resistance (PVR)and mean pulmonary arterial pressure (mPAP) in male PAH patients, whereas plasma ET-2significantly positively correlates with PVR and mPAP in female PAH patients. Functionally, wefound that recombinant ET-2 significantly inhibits proliferation of male pulmonary artery endothelialcells (PAECs), but significantly promotes proliferation in female PAECs. Similarly, ET-2 significantlyincreased proliferation of female pulmonary artery smooth muscle cells (PASMC), but not malePASMC. Together, we show that increased ET-2 expression may contribute to worsening PH bypromoting vascular remodeling in the lung and that elevated ET2 in females may at least partiallyexplain the higher incidence of female PAH patients
Abstract 4144567: Prevalence of Atrial Fibrillation in Amyloidosis and Their Association: A 5-Year Nationwide Analytical Cross-Sectional Study
Authors: Khatiwada Aliza , Tran Viet Nghi , Nguyen Doan Ngoc Chau , Bilo Thanh , Pham Hoang Nhat , Hoang Phu Thoai , Qadeer Tahira , Tran Phillip
Published: November 2024

Background:
Atrial fibrillation (AF) is a common cardiac arrhythmia associated with significant morbidity and mortality. Amyloidosis (AM) is characterized by the accumulation of amyloid protein in various anatomical sites, including the heart, atria, and ventricles. This amyloid infiltration leads to adverse chamber remodeling, predisposing patients to tachyarrhythmias such as atrial fibrillation/flutter. This study aims to re-evaluate the association of AM with AF by using the large nationwide inpatient database over a total duration of 5 years.

Methods:
An analytical cross-sectional study was conducted utilizing the data from a survey-weighted national inpatient sample database covering admissions from Jan 2017 to Dec 2021. A total of 147,015,073 admissions of patients aged 18 years and above were included. Descriptive statistics and univariate logistic regression models were used to calculate prevalence rates and odds ratios (OR), respectively. The multivariate logistic regression model was then used to adjust various potential confounders, including age, gender, race, income, hypertension, diabetes, stage 3 or above chronic kidney disease (CKD), Charlson comorbidity index, and hospital-related factors.

Results:
The 5-year prevalence of AF was 36.73% and 15.42% in admissions with and without AM, respectively. Significant differences between the with AM and without AM groups were in mean ages (72.40 vs. 58.08), female (41.83% vs. 56.92%), race of Black (24.57% vs. 15.40%), and CKD stage 3+ (44.83% vs. 16.65%), respectively. The univariate logistic regression analysis showed an OR for AF of 3.18 (95%CI: 3.102 - 3.267, P<0.000) in admissions with AM compared to those without. After adjustment for the potential confounders, the OR for AF decreased to 1.64 (95%CI 1.597- 1.686; P<0.000) in patients with Amyloidosis compared to those without.

Conclusion:
This study confirms a significant association between amyloidosis and atrial fibrillation, demonstrating that patients with amyloidosis have a markedly higher prevalence of atrial fibrillation compared to those without. Univariate analysis showed an odds ratio of 3.18 for atrial fibrillation in amyloidosis patients, which remained significantly elevated at 1.64 after adjusting for confounders. These findings indicate the need for a comprehensive workup of suspected atrial fibrillation in amyloidosis patients. Further research should investigate the mechanisms behind this association and potential prevention.
Abstract 4144573: Cardiac biomarkers, intensive lifestyle intervention, and risk of heart failure subtypes in type 2 diabetes – a post-hoc analysis of the Look AHEAD trial
Authors: Chunawala Zainali , Patel Kershaw , Segar Matthew , Garcia Katelyn , Bhatt Deepak , Wang Thomas , Januzzi James , Butler Javed , Lam Carolyn , Bertoni Alain , Espeland Mark , Pandey Ambarish
Published: November 2024

Background:
N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) identify subclinical heart failure (HF) in type 2 diabetes (T2D). The contribution of changes in cardiac biomarkers to HF risk, particularly HF subtypes, is unclear. Whether HF risk associated with cardiac biomarkers is modifiable with an intensive lifestyle intervention (ILI) targeting weight loss is unknown.

Methods:
Adults with T2D and overweight/obesity in the Look Action for Health in Diabetes (AHEAD) trial without prevalent HF were included. NT-proBNP and hs-cTnT were measured at baseline, 1- and 4-years (Roche Diagnostics). Adjusted Cox models were created to evaluate the associations of baseline, 1- and 4-year change in NT-proBNP and hs-cTnT with risk of HF with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Interaction testing was performed to evaluate heterogeneous effects of the ILI vs diabetes support and education (DSE) across baseline cardiac biomarkers.

Results:
Of the 3,959 participants included, 212 had incident HF (108 HFpEF, 84 HFrEF) over 12 years. Higher baseline NT-proBNP and hs-cTnT were each significantly associated with higher risk of HFpEF and HFrEF (
Table)
. Increases in NT-proBNP over 1- and 4-years were significantly associated with higher risk of HFpEF and HFrEF with a similar pattern of association for hs-cTnT and HF subtypes. After accounting for risk factor changes, the association of 1- and 4-year changes in NT-proBNP, but not hs-cTnT, with risk of HF subtypes remained significant. There was a significant interaction between NT-proBNP and ILI for risk of HFpEF but not HFrEF (p-int = 0.001). The ILI reduced HFpEF risk among participants with elevated (≥125 pg/mL) but not non-elevated NT-proBNP (<125 pg/mL) (ILI vs DSE HR [95% CI]: 0.48 [0.25-0.93] and 1.67 [0.94-2.94], respectively). No significant treatment group by hs-cTnT interactions were identified.

Conclusions:
In T2D, longitudinal changes in cardiac biomarkers, particularly NT-proBNP, are significantly associated with HF risk, independent of risk factor changes. In Look AHEAD, elevated NT-proBNP may identify individuals who are more likely to benefit from the ILI for HFpEF prevention.
Abstract 4144577: Temporal Trends in Attainment of LDL-c Goals Post Coronary Artery Bypass Grafting (CABG): Data From a Large Integrated Healthcare System
Authors: Yang Janine , Stram Douglas , Sheikh Ahmad , Ha Richard , Pursnani Seema
Published: November 2024

Introduction:
Multisociety guidelines in secondary atherosclerotic cardiovascular disease (ASCVD) cholesterol goals have evolved over time. We aim to identify temporal trends in low density lipoprotein cholesterol (LDL-c) and statin use in a post coronary artery bypass grafting (CABG) population.

Methods:
This is a retrospective study of Kaiser Permanente Northern California members who underwent CABG from 2008 to 2019. Patients were stratified according to three time frames (2008-2013, 2014-2018, 2019) based on the release of multisociety guidelines in 1999, 2013 and 2018. LDL-c goal was defined as a last available value less than 70 mg/dL at 1 year follow up. Lipid lowering therapies were identified through pharmacy records. Cox proportional hazard modeling was used to identify major adverse cardiovascular event (MACE) free survival at up to 12 years follow up.

Results:
The cohort included 6422 patients, mean age 64.9 years, 83% male, with baseline LDL-c 95.9 mg/dL. Of the cohort, 47% of patients achieved an LDL-c < 70 mg/dL at 1-year follow up. Of the stratified groups, the 2019 cohort demonstrated the highest attainment of LDL-c goal (65%, N=392) compared to 2008-2013 cohort (41%, N=1197) and 2014-2018 cohort (57%, N=1406) (Table 1). A relative increase in high dose statin monotherapy and a decrease in low/moderate dose statin monotherapy was temporally demonstrated in recent cohorts. There was a positive correlation between increasing year and attainment of LDL-c goal (R2=0.916) (Figure 1). Attainment of LDL-c <70 at 1 year post CABG was associated with higher MACE free survival (log-rank p=0.057).

Conclusions:
Recent cholesterol guidelines post ASCVD have a stronger emphasis on specified LDL-c goals which is associated with increased attainment of LDL-c <70 and improved MACE free survival in our post CABG patients.
Abstract 4144595: Real-World Outcomes of Impella 5.5 in Advanced Heart Failure Patients Undergoing Evaluation for Heart Transplant
Authors: Patel Khush , Suarez Erik , Guha Ashrith , Uy Ngo , Kim Ju , Akay Mehmet , Bhimaraj Arvind
Published: November 2024

Background:
Impella 5.5 provides robust support as temporary mechanical circulatory support (t-MCS) device in advanced heart failure patients in cardiogenic shock. Understanding short- and long-term outcomes is crucial.

Hypothesis:
Impella 5.5 supports advanced heart failure patients in cardiogenic shock and successfully bridges them to cardiac replacement without affecting long-term survival.

Methods:
From February 2020 to April 2024, all patients who received an Impella 5.5 and underwent evaluation for advanced therapies at Houston Methodist Hospital were identified. Implantation of Heartmate 3 (HM3) Left Ventricular Assist Device (LVAD), orthotopic heart transplantation (OHT), mortality, and device removal after Impella implantation were assessed. For HM3 LVAD patients, outcomes were categorized as death, transplantation, or survival. Survival after OHT was analyzed using Kaplan-Meier analysis and compared to patients who received OHT without Impella 5.5. Cumulative incidence rates was calculated using Competing risk regression.

Results:
140 patients were identified, median age 59.4 years (50.4-66.5), majority Caucasian (54%) and Black (36%). 89 (63.6%) were either bridged to advanced therapies or recovered. 52 (37.1%) underwent OHT, 21 (15%) received an HM3 LVAD, and 51 (36.4%) died post-implantation. 3 (2.1%) died post-transplant. Post-LVAD, 6 (4.3%) died, 3 (2.1%) underwent OHT, and 12 (8.6%) were alive with LVAD. 10 (7.1%) survived after Impella 5.5 removal, 2 (1.4%) went to hospice, and 1 (0.7%) was transferred to another hospital. 3 (2.1%) are currently hospitalized. Fig1a shows outcomes. Fig1b indicates death within 90 days of Impella implantation. 3-year survival of patients bridged with Impella to OHT (N=55) was 94%, comparable (p=0.27) to patients receiving OHT without Impella (N=215)(Fig 1c).

Conclusion:
Mortality for cardiogenic shock patients remains high. Using Impella 5.5 with a cardiac replacement strategy can salvage some patients. Long-term outcomes for patients bridged to heart transplant with Impella 5.5 are similar to those without the device. Further studies on predictors of early adverse outcomes post-implant can help mitigate risks for advanced heart failure patients in cardiogenic shock.
Abstract 4145819: Reducing the Burden of the Opioid Epidemic by Adopting a Novel Pain Control Strategy Utilizing Pectoral Nerve Block in Adults Undergoing Transvenous Cardiac Device Implants
Authors: Nair Ganesh , Gabrah Kirollos , Doty Brandon , Mahtani Arun , Nair Devi
Published: November 2024

Introduction:
Despite early mitigation efforts, the opioid pandemic in the United States has persisted and affected many Americans. A public health emergency was declared urging all prescribers to use caution in prescribing opioids. Alternative approaches to postoperative pain management during transvenous cardiac device implants (TCDI) in adults have not been described.

Methods:
We report a single-center retrospective analysis of 612 consecutive patients that underwent TCDI between January 2021 and January 2024 with ultrasound guided pectoral nerve block (PNB) using liposomal bupivacaine prior to implant for postoperative pain management. Pain scores (0-10) were recorded systematically in the postoperative period, at discharge, and at wound check follow-up. Any need for opioid use in the postoperative period was recorded as well.

Results:
A total of 612 patients were evaluated, 50% female with a mean age of 71.2 years. All patients received PNB successfully with no device site infection or hematomas. The mean Visualized Analog Scale (VAS) pain scores at 1, 3, and 5 hours after the procedure, at discharge, and at the follow-up visit were 1.93, 1.22, 1.10, 1.05, and 0.13 respectively. During follow-up, no patients required opioids for pain control throughout the entire postoperative period of 14 days.

Conclusion:
Pectoral nerve block with liposomal bupivacaine can be performed safely preoperatively during TCDI and provides adequate pain control without need for opioid use postoperatively. Further research is needed to assess broad scale implications of this approach to larger patient populations.
Abstract 4145857: The effect of homebase exercise training on single ventricle heart (SVH) function, exercise performance, body composition and quality of Life in children and adolescents living with a Fontan circulation
Authors: Ng Li Yen , McMahon Colin , James Adam
Published: November 2024

Objectives:
Fontan patients have impaired exercise capacity. Exercise training has been shown to improve exercise performance. We aim to determine the effect of exercise training on SVH function, and its correlation with exercise capacity, body composition and self-reported QOL.

Methods:
31 paediatric Fontan patients were prospectively recruited to complete 3x30 minute homebased HIIT sessions per week for 20 weeks. Baseline physical activity levels, including structured sports participation, daily step-counts and active-zone-minutes (AZM) were recorded by accelerometer (Fitbit inspire3). Patients were considered active if they met 2 of the 3 criteria:

1/Structured sports training ≥ 2 per week (moderate-vigorous intensity >30 minutes)

2/Daily steps ≥ 10k

3/AZM ≥60 minutes per day

Bio-impedance-analysis, cardiopulmonary exercise tests, echocardiography including deformation imaging and PedQL questionnaires were performed at baseline and upon completion.

Results:
28 participants completed the programme. 86% had good compliance (completed >45/60 sessions). 17 male (60.7%), mean age 14.3±2.03 years, 14 LV-dominant, 14 non-LV dominant (9RV, 5BiV). No serious adverse events reported.

The exercise duration improved from 7.56±2.6 to 9.16±2.5 minutes, p<0.001 and peak workload from 110±43.6 to 129±45.8 watts, p<0.001. Indexed oxygen consumption (VO
2
/kg peak) improved from 30.9±7.1 to 32.2±7ml/min/kg, p=0.003 and oxygen pulse, O
2
pulse
peak
from 9.1±2.6 to 9.7±3 mL/beat, p<0.001. Submaximal analysis showed normal %predicted VO2 (>40%) and improvement of O
2
pulse, p=0.024.

LV systolic function showed improved MAPSE from 1.65±0.2 to 1.86±0.2, p=0.017, and improved apical rotation from 2.3±3.8 to 5.9±3.1, p=0.043. RV systolic function showed improved TAPSE of 1.4±0.2 to 1.6±0.3, p=0.032 and FAC of 44±5.6% to 49±10.5%, p=0.170.

Self-reported QOL scores were higher in Fontan children who were physically active at baseline, with a downward trend noted when poor compliance was evident (Child’s QOL V3.0 91.21±0.7 to 86.1±5.2, p=0.018 (Table 2).

Although no significant change in body composition, a higher appendicular skeletal muscle mass, SMMa% and lower body fat% were noted pre and post exercise training in the active Fontan group (Table 3),

Conclusions:
We observed significant improvements in both the submaximal and peak exercise performance in paediatric Exercise training associated with improvement of single ventricle longitudinal systolic function and ventricular mechanics.