bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4141061: Predicting Mortality Risk In patients With Heart Failure Using Respiratory Polygraphy And Esophageal Pressure During Sleep
Authors: Nahoui Hamza , Schirmer Henrik , Hrubos-Stroem Harald 
Published: November 2024

Background:
Expansion of thorax and abdomen during normal respiration generates negative intrathoracic pressure that affects organs like the heart and esophagus. Upper airway collapse during sleep increases respiratory effort. Measuring esophageal pressure (PES) is the gold standard for estimating this effort.

Heart failure is highly associated with obstructive sleep apnea (OSA). Abrupt swing in thoracic pressure and nocturnal hypoxemia during apnea are two mechanisms that can lead to heart failure.

Hypothesis:
PES and traditional sleep metrics: apnea hypopnea index (AHI), oxygen desaturation index (ODI), and mean-spO2 are associated with increased mortality risk in patients with heart failure and OSA.

Methods:
174 patients with heart failure identified in the local heart failure registry in Akershus university hospital. All patients underwent respiratory polygraphy and esophageal manometry during sleep. Observation time 2003-2024.

AHI, ODI, mean-spO2 and sleeping time with elevated esophageal pressure above different cmH2O, PES, were measured. Initial proBNP were also analyzed. Cox proportional hazard models were used to analyze the risk. Results were adjusted to age, sex, body mass index (BMI), and comorbidities.

Results:
Mean age 66 years (SD 12.019). 34 (20%) of observed cases were females. 70 (40%) patients died during observation time. Mean time to event (death) from first proBNP 3,5 years. Mean time to event from baseline polygraphy 8,2 years.

First proBNP predicted all-cause mortality (HR 1.108 [95% CI 1.052-1.167], p<0,001). AHI>15, ODI and mean-spO2 during sleep predicted all-cause mortality, but not sleep time with elevated esophageal pressure above 15 cmH2O. Sleep time with higher pressure degrees (above 80 cm H2O) did predict mortality.
Adding first proBNP to our prediction model did not affect the predictive value of mean-spO2 (HR 0.828 [95% CI 0.752 -0.912], p<0.001), or sleep time with PES above 80 cmH2O (HR 1.127 [95% CI 1.003-1.1.265], p 0.043).

Conclusion:
Nocturnal mean-spO2, and PES above 80 cmH2o predicted mortality in patients with heart failure and sleep apnea independent of first proBNP values.

Our results might explain why treatment with positive airway pressure is more effective in patients with severe OSA, and that oxygen therapy during sleep could represent a treatment choice for patients with HF and OSA.
Sleep studies may offer prognostic value for heart failure patients several years before first proBNP is obtained.
Abstract 4141178: Papillary fibroelastomas: clinical presentation, anatomical characteristics, and bleeding rates in those undergoing surgical and conservative management
Authors: Saleh Hassan , Khaleel Ibrahim , Korn Morgan , Alameh Saleem , Sarkisov Mitchell , Dils Anthony , McNamara David 
Published: November 2024

Papillary fibroelastomas (PFEs) are benign cardiac tumors, most commonly arising on left sided heart valves but have been reported on non-valvular structures. Histologically, PFEs are comprised of throngs of an avascular mucopolysaccharide core with an overlying layer of endothelial cells. While PFEs carry no inherent malignant potential, the risk of embolization poses a unique challenge to clinicians.
Case series exist describing the anatomical characteristics of PFEs, though as echocardiography has become more ubiquitous and imaging quality has dramatically improved, little contemporary data exists on the patient characteristics, management techniques employed, and outcomes. Our objective was to describe a quaternary center’s experience with PFEs.
A single quaternary center, retrospective case review of patients with a diagnosis of cardiac tumor between Janurary 1 2008 and Janurary 30 2024, using ICD codes D15.1 and I42.4, resulted in 410 patients. Using chart review, 80 of the 410 patients had a suspected diagnosis of PFE based on TEE or TTE characteristics. We then performed a retrospective analysis of the 80 patients.
Of the 80 patients, 47 underwent surgical resection, 5 roboticly, with no evidence of PFE on subsequent TTE. The median age at time of diagnosis was 67.7 +/- 13.8 years. 35 patients had a diagnosis of stroke any time prior to PFE identification. The most common indication for the diagnostic echocardiogram was arterial emboli. Valvular PFEs were commonly found on the upstream aspect of valves (55.9%) and most commonly located on the aortic valve (63.8%). Of the 27 patients with a diagnosis of stroke and PFE size data, 20 had a PFE >/= 5 mm. In the non-surgical group 7 were on P2Y12 inhibitor or therapeutic anticoagulation for the indication of PFE. Within 3 years there was 1 mortality in the surgical group and 6 in the non-surgical group. In the non-surgical group 15.2% were hospitalized for bleeding at 3 years verse 6.25% in the surgical group.
While PFEs have been previously characterized in case series, there remains a scarcity of literature on their clinical presentation and management techniques. This single center case series demonstrates an association between PFEs and arterial embolic events with low three-year mortality. There may be a relation to PFE size and stroke as stroke was more common in those with a PFE >/= 5mm. Additional studies evaluating PFE characteristics and treatment strategies are necessary to guide PFE management.
Abstract 4141698: Outcomes of catheter ablation in cardiac sarcoidosis patients with ventricular tachycardia
Authors: al taii haider , Saxena Ritika , Gaalema Diann , Narayanan Chockalingam , Morcos Ramez , Sabayon Muhie Dean , Jneid Hani 
Published: November 2024

Background:
Ventricular tachycardia (VT) in patients with cardiac sarcoidosis (CS) can lead to sudden cardiac death. The role of ventricular tachycardia ablation (VTA) in CS has been investigated in a few small, single-center, and some larger observational studies, but the evidence remains scarce.

Hypothesis: We hypothesize that patients with CS have worse cardiovascular outcomes.
Aims: This study aimed to investigate the clinical outcomes of VTA in patients with CS admitted with a diagnosis of VT.

Methods:
A retrospective analysis was conducted using TrinetX database: US collaborative network from 2010-2024. Patients undergoing ablation for VT with and without CS were identified. Two groups were created for propensity score analysis matching on history of hypertension, diabetes, obesity, peripheral vascular diseases, heart failure, ischemic heart diseases, atrial fibrillation, and chronic kidney disease. The primary outcome was incidence of death, cardiogenic shock, heart failure, acute myocardial infarction, hemorrhagic stroke, ischemic stroke, and ventricular tachycardia within one year from the date of the index procedure.

Results:
Results: Out of 15,958 patients who underwent catheter ablation for VT, 776 patients had CS. The mean age of patients with VT and CS who underwent ablation was 58.6 (SD:11.3), compared to 61.1 (SD:15) in patients with VT without CS. In the propensity-matched analysis, there was no significant difference in one-year mortality (hazard ratio (HR) 0.65; 95% CI [0.45, 0.94], χ2 = 3.05, p = 0.08), heart failure (HR 1.18; 95% CI [1.04, 1.33], χ2 = 1.5, p = 0.2), cardiogenic shock (HR 1.33; 95% CI [0.95, 1.89], χ2 = 0.005, p = 0.94), acute myocardial infarction (HR 0.81; 95% CI [0.5, 1.11], p = 0.67), hemorrhagic stroke (HR 0.89; 95% CI [0.18, 4.41], p = 0.42), ischemic stroke (HR 1.18; 95% CI [0.80, 1.7], p = 0.79) or ventricular tachycardia (HR 1.17; 95% CI [1.04, 1.31], p = 0.19)

Conclusion:
This analysis shows there is no significant difference in major complications in patients with cardiac sarcoidosis undergoing catheter ablation for ventricular tachycardia compared to patients without cardiac sarcoidosis.
Abstract 4145451: Efficacy of Left Atrial Appendage Occlusion with Watchman Device in the Population with BMI>25
Authors: Mir junaid , Alraies M Chadi , Al-Ahmad Majd , Al-Ahmad Anas 
Published: November 2024

Background:
Left atrial appendage closure (LAAC) with Watchman device is an alternative strategy to oral anticoagulation for decreasing ischemic stroke risk in selected patients with non –valvular atrial fibrillation (AF). There is a paucity of data about the efficacy of watchman device in overweight/obese population.

Methods:
We queried the National Inpatient Sample of the years 2016 to 2020. We identified patients who were admitted for Watchman procedures using ICD10-PCS codes. The risk of mortality and in-hospital complications in overweight/obese group was compared to the non–overweight/non obese group using multivariate logistic regression analysis.

Results:
During 2016-2020, there were a total of 90060 patients who were admitted for Watchman procedure, of which 15765(17.5%) patients were overweight or obese while 74295 (82.5%) were neither obese nor overweight. After adjusting for demographics, watchman procedure in overweight/obese population had higher odds of arrhythmia (aOR (adjusted odds ratio) 1.19; 95% CI 1.08–1.31 p <0.001), AKI (aOR 1.32; 95% CI 1.03–1.68p =0.026), respiratory failure (aOR 1.52; 95% CI 1.16–1.98 p =0.02), and non-invasive ventilation (aOR 1.9; 95% CI 1.33–2.7 p<0.001). There were no differences in mortality, GI bleed, Length of stay (LOS) and mean total cost of care between the two groups.

Conclusion:
Left atrial appendage occlusion with Watchman device in overweight /Obese population

has higher odds of arrhythmia, AKI, respiratory failure, and non –invasive ventilation
compared to non-overweight/non obese population. Further studies are needed to
elucidate the benefit of Watchman device in the overweight/obese population.
Abstract 4145572:
LMNA
p.Q353R Mutation Causes Dilated Cardiomyopathy through Impaired Vitamin D Signaling
Authors: Ito Masamichi , Katoh Manami , Nomura Seitaro , Komuro Issei 
Published: November 2024

Introduction:
Dilated cardiomyopathy (DCM) is one of the causative diseases of heart failure, caused by genetic mutations. Cases with mutations in the
LMNA
gene, which encodes lamin A/C protein and constitutes the nuclear lamina, are known to have a poor prognosis. We have previously shown that the DNA damage accumulation and the consequent activation of DDR in cardiomyocytes are the cause of cardiac function impairment. However, the method to reduce DNA damage in the heart has not been elucidated. Therefore, we decided to explore the compounds that could reduce it in the cardiomyocytes.

Methods and Results:
We generated iPS cells from DCM patients with a LMNA mutation (p.Q353R) and differentiated them into cardiomyocytes. The mutant cardiomyocytes showed severe deformation of nuclear morphology as well as reduced contractility. In addition, the number of positive foci for γH2AX, a DNA double-strand break marker, was increased in the nuclei of the mutant strain. These results indicate that in vitro disease modeling using iPS cell-derived cardiomyocytes was successfully achieved.

We administered a library of 175 compounds to the mutant cardiomyocytes to search for compounds that reduce the positive foci of γH2AX. We found that vitamin D2 (VD2) significantly reduced DNA damage in the mutant strains. RNA-seq analysis revealed that VD2 restored the expression of DNA repair enzymes that were downregulated in the mutant strains.
We then screened binding molecules of the mutant LMNA p.Q353R protein and wild-type LMNA protein using a protein array. The screening results showed that the binding to the vitamin D receptor (VDR) was significantly enhanced in the mutant protein compared to the wild-type protein. In the mutant cardiomyocytes, VDR was localized to the periphery of the nuclear membrane, and reporter assays showed decreased transcriptional activity of VDR.
Finally, we examined the effects of VD2 on DNA damage accumulation and cardiac function in vivo. VD2 analog reduced DNA damage accumulation and improved cardiac function in two mouse models: a pressure-loaded heart failure model and a Lmna nonsense mutant cardiomyopathy model.

Conclusion:
Using patient-derived iPS cells, we could recapitulate various pathological processes in diseased cardiomyocytes, as well as identify therapeutic candidates through compound screening. One of the existing drugs, VD2, was a hit in this screening, and clinical trials for drug repositioning are expected.
Abstract 4146005: Cardiogenic Shock secondary to Acute Structural Valve Dysfunction of an Avalus Bioprosthesis in a Patient with Two Prior Valve Replacement Surgeries - Third Time’s the Charm
Authors: Matute-Martinez Carlos , Twayana Anu Radha , GUMPU SIVASHANKAR PRASHANTH , TABOWEI GODFREY , Tabatabaei Yeganeh Hanieh , Watts Abi , Boccalandro Fernando 
Published: November 2024

Aortic valve replacement (AVR) with biological valve prostheses (BV) avoids long-term anticoagulation compared with mechanical vale prostheses. Their durability is limited due to structural valve dysfunction (SVD). Valve degeneration is gradual, leading to bioprosthetic valve failure (BVF). We present the first case reported of acute aortic Avalus bioprosthesis SVD with severe aortic regurgitation (AR) secondary to flail leaflet.

A very active 52-year-old male with CAD, atrial fibrillation/flutter, and bicuspid aortic valve (AV) with symptomatic severe aortic stenosis treated with a 25 mm Abbott St. Jude/EPIC
TM
Supra valve 16 years ago required a redo surgery for infective endocarditis with an aortic root abscess treated with a 25 mm Medtronic Avalus BV 5 years prior and aortic root reconstruction. He presented with a 3-day history of chest pain and severe dyspnea. On arrival, cardiogenic shock and respiratory failure ensued, requiring vasopressors and endotracheal intubation. CXR revealed pulmonary edema. Coronary angiogram revealed non-obstructive CAD. TEE revealed preserved LV function with severe acute AR. He underwent emergent AVR. Surgery revealed a sterile flail prosthetic valve leaflet with complete prolapse of the noncoronary cusp. A 27-mm Medtronic Evolute BV was placed. His course was complicated by transient complete heart block. He continued improving and was then discharged.

Acute AR should be suspected in patients with acute hemodynamic instability and history of AVR. TTE or TEE are crucial for the assessment of BV and diagnosis of AR. The only effective treatment for acute severe AR is emergent AVR. Newer generation BVs offer the possibly of not requiring long-term anticoagulation and enhanced durability. The PERIGON trial evaluating the Avalus bioprosthesis in AVR showed no cases of SVD with excellent durability and hemodynamic profile during the 5-year follow-up, being this the first case reported in the literature of acute catastrophic failure of this valve.
Our case highlights the importance of rapid diagnosis and intervention in acute aortic BVF. While newer BVs offer improved durability and hemodynamic properties, clinicians must remain vigilant for acute complications secondary to SVD. Studies with longer follow-up are needed to better characterize the safety and performance of the Avalus bioprosthesis. The lack of standardized definitions for SVD may have led to underreporting and underestimation of its incidence.
Abstract 4146686: Carvedilol Exerts Evolutionarily Conserved Cardioprotective Effects via Autophagy Modulation and Energetics Restoration
Authors: Boukhalfa Asma , SHIN PEI-TSZ , Meola Dawn , Showers Annie , Yu Ada , Upshaw Jenica , London Cheryl , Jaffe Iris , Pulakat Lakshmi , Yang Vicky , Chen Howard 
Published: November 2024

Carvedilol (CAR) is an FDA-approved adrenergic blocker commonly given to cardiovascular disease patients. Interestingly, CAR also shows anti-cancer potential in reducing cancer-specific mortality in breast cancer patients. To advance CAR usage in cardio-oncology, we hypothesize that elucidating the molecular mechanism of the energy sensing and homeostasis pathways underlying CAR’s cardioprotective capabilities can enhance its clinical translation.
Canine cardiac slices were generated from 3 euthanized pet dogs free of cardiovascular disease. CAR pretreatment (1μM, 4 hrs) with or without a 24-hr exposure to 5μM of cardiotoxic doxorubicin (DOX) was performed. Murine slices from 5 C57Bl6 mice with the same treatments as above was also performed. Direct tissue imaging on IVIS Spectrum was carried out to assess apoptosis by Annexin V staining, autophagy with autophagy detecting nanoparticle (ADN) developed in-house, and DOX retention in tissue by the inherent DOX fluorescence. Tissue was analyzed by histological staining of apoptosis and Western blot of autophagy and energy sensing pathways. Energetics quantified by Seahorse assay was performed in isolated mitochondria from cardiac slices in rat cardiomyoblasts (H9C2 cells) and human iPSC-induced cardiomyocytes (iCells).
In both canine and murine cardiac slices, autophagy was significantly reduced (p<0.05) by DOX while apoptosis was significantly increased (p<0.05), both of which were reversed by CAR. CAR did not change DOX fluorescence in tissue. Western blot of autophagy biomarkers LC3, p62 and Beclin-1 confirmed that autophagy impaired by DOX was restored by CAR. The beneficial autophagy restoration by CAR was modulated by a significantly increased phosphorylation of AMP kinase (AMPK), a key energy sensing pathway that activates autophagy via significantly reducing mTOR (p<0.0001). In mitochondria isolated from cardiac slices, basal respiration and ATP production that were significantly impaired by DOX were rescued (p<0.0001) by CAR. Similar rescue of basal respiration and ATP production by CAR was seen in murine and human cardiomyocytes, suggesting that CAR exerts a direct protective effect on the at-risk cardiomyocytes during DOX stress.
We demonstrated for the first time in human, canine, and murine that CAR targets the AMPK pathway to activate autophagy, reduce cardiomyocyte apoptosis, and restore mitochondrial energetics, thus with immense translational potential in cardioprotection.
Abstract 4147025: Obesity as an Underlying Driver of Differences in Racial and Socioeconomic Disparity Associated Cardiac DNA Methylation Among Men with End-stage Heart Failure
Authors: Chang Samuel , Preuss Kerstin , Lin Benjamin , Bakshi Sayan , Miller C. Ryan , Wende Adam 
Published: November 2024

Heart failure (HF) treatment advances have improved outcomes but HF heterogeneity leads to ~50% response to standard therapies, emphasizing a need to further study mechanisms of disparate outcomes. One serious disparity is increased cardiovascular disease risk and mortality in African Americans (AA) compared to Caucasian Americans (CA). Race is a social construct and thus poor proxy for physiology; hence, our lab studies epigenetics, stable yet reversible changes to DNA serving as a possible interface of how environment impacts gene regulation. We’ve previously implicated cardiac DNA methylation as a new indicator of socio-economic disparities in HF outcomes. Related to HF, US adult obesity rates are 40% and similar disparities exist with AA having higher rates, and studies on obesity show how inequity leads to disparate rates. Thus, our secondary analysis investigates the role of obesity, through its impact on cardiac epigenetics and transcription, as an underlying environment/molecular driver within HF disparities.
Multi-omics data of left ventricular assist device placement biopsies of age-matched males were from our previous publication’s public dataset. Cardiac DNA methylation (850k-array) analyzed via minfi, and differential gene expression (RNA-seq) via DESeq2.

Two-year survival is decreased in non-obese (NO) vs. obese (OB) patients (p<0.01); specifically, decreased survival in AA-NO patients vs. CA-NO patients (Hazard Ratio=0.26, 0.08-0.91). Subgroup analyses reveal 2632 gene-associated differentially methylated CpG-probes between AA-NO vs. OB, and 5309 between CA-NO vs. OB (p<0.05, |methyl-change|>5%). Additionally, 19 differentially expressed genes between AA-NO vs. OB, and 236 between CA-NO vs. OB (q<0.1, |Log FC|>1.5); one key gene, TNFa induced protein 8 (
TNFAIP8
), is increased in AA-NO vs. OB, but decreased in CA-NO vs. OB. Furthermore, the differential expression in each group correlates with canonical significant inverse DNA methylation at
TNFAIP8
.

Our survival data supports the literature of an “Obesity Paradox” where obese HF patients have better prognoses than non-obese patients. Through our analyses, we characterized impacts of obesity status on DNA methylation and gene expression within disparate HF outcomes and identified
TNFAIP8
as a marker related to increased apoptosis in pathology progression. Thus, our work contributes molecular characterization of a possible effector of the differences seen in these specific patient populations.
Abstract 4147484: Association Between Protein Energy Malnutrition and Transplant Rejection in the Heart Transplant Population. A Retrospective Inpatient Database Analysis
Authors: Evbayekha Endurance , OMOIKE EUGENE , Alugba Gabriel , sajja jayadev , Younis Uthman , REISS CRAIG 
Published: November 2024

Introduction:
Heart transplant (HT) is the gold standard for advanced heart failure, and the individuals burdened by advanced heart failure often have multiple comorbidities. Protein-energy malnutrition (PEM) is a common comorbidity and is frequently underdiagnosed. Previous studies examined the relationship between PEM and mortality in HT and found a positive association. However, the relationship between PEM and HT rejection, HT failure, and cardiac allograft vasculopathy (CAV) is scarce. Given that these complications also impact survival, we sought to explore the relationship.

Methods:
We identified all HT patients using ICD-10 codes from the 2016 to 2021 National Inpatient Sample database. Then, the PEM group was compared to the no-PEM group. We used Student’s Test and Pearson’s Chi-squared to analyze continuous and categorical variables. Then, multivariable logistic regression models were used to account for confounders and to predict the outcomes. The primary outcomes were HT rejection, HT failure, and CAV. The secondary outcomes were mortality, arrhythmias (composite of atrial and ventricular fibrillation and flutter, and supraventricular tachycardia), length of hospital stay, and cost of hospitalization. A 2-sided p-value was the statistical threshold for significance.

Results:
During the study period, 31,215 HT hospitalizations occurred, and 11.9% (3,700) had PEM. The median age for the PEM group was 65 years.

Compared to the no-PEM group, HT rejection 0.8 (0.4-1.5), HT failure 0.8 (0.3-2.1), and CAV 1.08 (0.6-1.9) did not differ between both groups, p>0.05, each.
The PEM group had a higher association with mortality 2.8 (2.1-3.6), arrhythmias 1.4 (1.07-1.8), longer LOS 8 vs. 4 days, and higher cost of hospitalization, $84,687 vs. $43,285, p<0.01 each.

Conclusion:
Among the heart transplant population, protein-energy malnutrition was not associated with transplant rejection, transplant failure, or CAV. However, protein-energy malnutrition was associated with mortality, arrhythmias, a longer hospital stay, and a higher cost of hospitalization.