bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4132820: S-nitrosylation of cardiac Cx43 hemichannels at Cys271 promotes arrhythmogenicity and myocardial injury upon cardiac stress in Duchenne Muscular Dystrophy
Authors: Munoz Camus Manuel , Quan Jonathan , Nguyen Thao , Nuno Janet , Sheehy Adrian , Gaete Pablo , Lillo Mauricio , Contreras Jorge
Published: November 2024

Connexin-43 (Cx43) plays a critical role in the propagation of action potentials among cardiomyocytes and proper cardiac contractility. In healthy cardiomyocytes, Cx43 is located at the intercalated disk; however, Cx43 remodeling is observed in cardiac pathologies and is linked with arrhythmogenesis and sudden cardiac death. Utilizing a mouse model of Duchenne muscular dystrophy (DMD
mdx
), we have previously demonstrated that cardiac Cx43 is laterally localized, forming undocked hemichannels that activate via S-nitrosylation in response to isoproterenol-evoked cardiac stress. This activation leads to the disruption of cardiac membrane permeability, triggered activity, and deadly arrhythmogenic behaviors. To establish the direct role of S-nitrosylated Cx43 in DMD cardiomyopathy, we developed a specific knock-in mouse line in which the single Cx43 site for S-nitrosylation, cysteine 271 (Cys271), was substituted with a serine (C271S
+/-
). Here, we developed a DMD
mdx
:C271S
+/-
line (4–6 months old), exhibiting reduced levels of S-nitrosylated Cx43 after crossing DMDmdx mice and C271S
+/-
mouse lines to assess the effect of β-adrenergic stimulation-induced cardiac stress and heart dysfunction. We show that cardiac Cx43 remodeling was not prevented in DMD
mdx
:C271S
+/-
, similar to what was shown in DMD
mdx
mice via immunofluorescence analysis. In addition, DMD
mdx
mice displayed an increased number of deadly arrhythmogenic events, increased Ca
2+
signaling, and prolonged action potentials in Langendorff-perfused whole hearts via optical mapping, compared to wild-type and DMD
mdx
:C271S
+/-
mice. Similarly, isoproterenol treatment evoked severe myocardial injury, increased levels of plasmatic cardiac troponin I (cTnI), and 40% mortality in DMD
mdx
mice. Notably, DMD
mdx
:C271S
+/-
mice, similar to DMD
mdx
mice treated with the Cx43 hemichannel blocker Gap19, exhibited cardioprotection compared to the cardiac dysfunction observed in DMD
mdx
mice. Therefore, these findings strongly suggest that S-nitrosylation of Cx43 proteins at site Cys271 represents a fundamental NO-mediated mechanism involved in the induction of arrhythmias and myocardial injury in DMD
mdx
after β-adrenergic stress.
Abstract 4133654: External Validation of the Guha-Stabellini CVD Prostate Cancer-Specific Calculator in Short-Term Follow-Up
Authors: Stabellini Nickolas , Elsayed Omar , Agarwal Neeraj , Cullen Jennifer , Weintraub Neal , Hyma Kunhiraman Harikrishnan , swami umang , Mahmoudi Morteza , Shanahan John , Montero Alberto , Guha Avirup
Published: November 2024

Introduction:
Conventional cardiovascular disease (CVD) risk scores are inaccurate for prostate cancer patients (PC); the Guha-Stabellini machine learning (GS-ML) score shows promise but lacks external validation.

Hypothesis:
The GS-ML score is superior to conventional CVD scores in patients with PC.

Aim(s):
To conduct external validation of the GS-ML score in patients diagnosed with PC.

Methods:
The validation used holdout data from Seidman Cancer Center’s CAISIS platform (internal validation cohort) and RADICAL PC1 (external validation cohort; a prospective study of men diagnosed with PC within 1 year or starting ADT within 1 month of enrollment), matching covariates with the GS-ML score. With limited follow-up, short-term CVD (2,000 days from PC diagnosis) was the outcome. Performance was assessed via area under the receiver operating characteristic curve (AUC) with assistance from Youden statistic cutoff, comparing metrics with ACC/AHA pooled cohort equations (PCE), SCORE-2, and AHA-PREVENT scores. Atherosclerotic cardiovascular disease (ASCVD) included non-fatal ischemic stroke and myocardial infarction. CVD included ASCVD and heart failure.

Results:
We included 2,495 patients from RADICAL PC1 and 1,506 from the internal validation cohort (
Table 1
). In the internal validation cohort, the CVD AUCs were 0.58, 0.49, 0.65, 0,73, and 0.75 for PCE, SCORE2, PREVENT simple, PREVENT enhanced, and GS-ML score, respectively. In RADICAL PC1, the AUCs for CVD were 0.60, 0.43, 0.67, and 0.64 for PCE, SCORE2, PREVENT simple and GS-ML score, respectively. For ASCVD, internal validation cohorts’ AUCs were 0.63, 0.62, 0.66, 0.73, and 0.67 for PCE, SCORE2, PREVENT simple, PREVENT enhanced, and Guha-Stabellini, respectively. The RADICAL PC1 ASCVD AUCs were 0.64, 0.46, 0.65, and 0.61, for PCE, SCORE2, PREVENT simple and GS-ML scores, respectively,

Conclusion(s):
The GS-ML score was validated for PC patients, showing superior performance to PCE and SCORE2, and similar performance to AHA-PREVENT in predicting CVD. The European Cardio-Oncology guidelines should reconsider using SCORE2 for PC patients. Further improvement and validation with nationally representative datasets are needed to corroborate these findings and enhance the generalizability of the GS-ML score.
Abstract 4134234: Association Between the Natriuretic Peptides-Cyclic Guanosine Monophosphate Cascade and Left Ventricular Reverse Remodeling After Acute Anterior Myocardial Infarction
Authors: Arai Marina , Asaumi Yasuhide , Honda Satoshi , Ogata Soshiro , Kiyoshige Eri , Miura Hiroyuki , Nakao Kazuhiro , Murai Kota , Iwai Takamasa , Sawada Kenichiro , Matama Hideo , Fujino Masashi , Yoneda Shuichi , Takagi Kensuke , Takahama Hiroyuki , Otsuka Fumiyuki , Kataoka Yu , Nishimura Kunihiro , Noguchi Teruo , Minamino Naoto , Yasuda Satoshi
Published: November 2024

Background:
Natriuretic peptides and their second messenger, cyclic guanosine monophosphate (cGMP), play a critical role in the pathogenesis of cardiovascular diseases by inhibiting the renin-aldosterone system, cardiac hypertrophy, and fibrosis. Recently developed chemiluminescent enzyme immunoassays for proBNP have enabled the estimation of mature BNP (emBNP) by calculating the difference between total BNP and proBNP.

Research Questions:
The role of cGMP in left ventricular remodeling after acute myocardial infarction (AMI) remains poorly understood.

Aims:
We aimed to investigate the relationship between the natriuretic peptide-cGMP cascade and left ventricular reverse remodeling (RR) in patients with anterior AMI.

Methods:
In a prospective 67 patients experiencing their first anterior AMI, plasma BNP fractions and cGMP levels were measured at immediate primary percutaneous coronary intervention (PPCI), 3 days, and 3 months post-AMI. Change in left ventricular end-systolic index (delta-LVESVI) was calculated as the difference between median 10 months and day 10 using cardiac magnetic resonance imaging. Patients were divided into RR and non-RR groups based on regression analysis to compute residuals representing the differences between each individual’s observed delta-LVESVI and delta-LVESVI adjusted by plasma pro-BNP concentration at immediate PPCI because of an inverse correlation between delta-LVESVI and plasma pro-BNP concentration at immediate PPCI (r=0.243, p=0.047). RR group (n=33) demonstrated below-median residual delta-LVESVI, while non-RR group (n=34) had above-median residual.

Results:
RR group exhibited significantly higher freedom from major adverse cerebral and cardiovascular events (MACCE) during a median of 8.1-year (Interquartile range: 6.7–8.8) follow-up (P=0.024)
(Figure A)
. Multivariable analysis identified logarithmic plasma pro-BNP, and emBNP at day 3 post-AMI, and plasma cGMP levels at immediate PPCI and day 3 post-AMI, as independent predictors of RR (P<0.05) even after adjusting age, male, hypertension, and infarct size.
(Figure B-D)
.

Conclusion:
Early-phase activation of the natriuretic peptides-cGMP cascade may play a protective role in left ventricular remodeling in patients with anterior AMI.
Abstract 4134345: Diastolic Dysfunction And The Risk Of Stroke And Major Bleeding
Authors: Kundrick John , Saba Karina , Naniwadekar Aditi , Singla Virginia , Mulukutla Suresh , Thoma Floyd , Bhonsale Aditya , Kancharla Krishna , Voigt Andrew , Shalaby Alaa , Estes Nathan , Jain Sandeep , Saba Samir
Published: November 2024

Background:
Diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes including atrial fibrillation. Whether DD is independently associated with incident ischemic stroke/transient ischemic attack (TIA) and with bleeding events is not well established.

Aims:
To examine the association of presence and severity of DD with the risk of incident ischemic stroke/TIA and major bleeding.

Methods:
A total of 219,667 patients who underwent at least one echocardiogram between 2010 and 2022 at a large academic institution and were followed for at least 3 months were included. Patients with prior history of stroke or TIA (n=21,505, 10%) were excluded. Smart key-phrase search was applied to echocardiographic reports to classify patients into 4 groups, based on the most severe DD assessment: Normal (n=113,265), grade I (n=21,981), grade II (n=7,215), and grade III (n=1,627). Patients in whom the presence of DD could not be determined (n=54,074) were excluded. The final study cohort (n=144,088) was followed to the endpoint of hospital admission for ischemic stroke/TIA or for major bleeding.

Results:
Over a median follow-up of 3.4 years, 3482 (2.4%) patients were hospitalized for stroke/TIA and 6994 (4.9%) for major bleeding. After adjusting for several confounding variables (Table), DD remained a strong predictor of incident stroke/TIA (hazard ratio (HR)=1.34 per grade increase in DD, p<0.001, Figure) and of major bleeding (HR=1.32 per grade increase in DD, p<0.001, Figure). These results were similar in patients with (n=11,508, 8%) or without prior history of atrial fibrillation.

Conclusions:
Patients with DD have a heightened risk of ischemic cerebrovascular accidents and major bleeding independent of the presence of atrial fibrillation. These risks escalate with the severity of DD. DD should be considered when counseling patients regarding their risk profile and management options.
Abstract 4134379: Mediterranean-Style Diet and Adverse Pregnancy Outcomes by Race and Overweight or Obesity Status in the Boston Birth Cohort
Authors: Tran Linh , Hong Xiumei , Boyer Theresa , Wang Xiaobin , Minhas Anum
Published: November 2024

Introduction:
Mediterranean-style diet (MSD) is associated with a lower risk of cardiovascular and metabolic diseases. However, the association of MSD during pregnancy with adverse pregnancy outcomes (APOs) among different racial and ethnic groups and overweight or obesity (OWO) status remains unclear.

Question:
We examined if MSD during pregnancy is protective for developing any APO and individual APOs in a large cohort of racially and ethnically diverse, urban, low-income women.

Methods:
Among 8,511 patients in the Boston Birth Cohort (mean age 28.2±6.5 yrs), 47% were non-Hispanic Blacks and 28% were Hispanics. Among 4,343 (51%) with pre-pregnancy OWO status, 25% Black and 12% Hispanic women developed any APO (Figure 1). Individual Mediterranean-style diet score (MDS) was based on maternal diet intake during pregnancy via food frequency questionnaire interviews at 24-72 hours postpartum.

Results:
Increase in the MDS by one standard deviation was inversely associated with any APO (aOR, 0.86 [95% CI, 0.82–0.90]), preeclampsia or eclampsia or HELLP (aOR, 0.89 [95% CI, 0.82–0.97]), gestational diabetes (aOR, 0.88 [95% CI, 0.81–0.95]), preterm birth (aOR, 0.90 [95% CI, 0.86–0.95]), and low birth weight (aOR, 0.87 [95% CI, 0.83–0.92]) (Table 1). In the subgroup analysis, higher adherence to MSD was associated with lower odds of developing, preeclampsia or eclampsia or HELLP, low birth weight, and preterm birth in Black women with or without OWO. The benefit of MDS was also observed for gestational diabetes in Hispanic women with OWO (Figure 2).

Conclusion:
Greater adherence to MSD during pregnancy is associated with a lower risk of composite APOs, with benefits varying across types of APOs, racial/ethnic groups, and OWO status.
Abstract 4134475: Effects of E-cigarette Vaping on Endothelial Function in Diet-Induced Obese Mice
Authors: Le Hoai Huong , Liu Chen-Wei , Attaluri Anika , Denaro Philip , Nguyen Yen , Nguyen Jennifer , Barney Alyssa , Wendt Trevor , Gonzales Rayna , Hale Taben , Lee Won Hee
Published: November 2024

Introduction:
Although electronic cigarettes (e-cigs) have been known to increase the risk of vascular complications, little is known about whether e-cig represents an independent risk factor for the development and worsening of obesity and its associated vascular diseases. We hypothesize that a high-fat diet (HFD) enhances e-cig-induced vascular complications.

Methods:
Male and female eight-week-old C57Bl/6J mice were fed normal chow (NC) or HFD for 15 weeks before being exposed to e-cigs (PG/VG only [PGVG] or PG/VG + 24 mg/ml nicotine [Nic]) or fresh air (FA) for 12 weeks (n=6-8). At the end of the experiments, glucose level and thoracic aortic responses to phenylephrine (PE), acetylcholine (ACh), and sodium nitroprusside (SNP) were assessed via the glucose tolerance test (GTT) and wire myography, respectively. Total RNA from male aortas was extracted and RNA-seq was utilized to identify the transcriptomic changes in our diet-induced obesity mouse model subjected to e-cig vapors (n=4).

Results:
Compared to NC with FA, HFD alone caused glucose intolerance as shown by the GTT, which was improved only by exposure to nicotine-containing e-cigs (HFD+Nic). Similar improvement in glucose intolerance were found in the NC group with e-cigs (PGVG or Nic). In addition, both NC and HFD-fed male mice exhibited endothelial dysfunction characterized by a decrease in the ACh-dependent (endothelium) relaxation of PE-induced contractions. Importantly, nicotine-containing e-cig exposure (Nic) dramatically reduced the sensitivity of the aorta in the HFD group (HFD+Nic) to both ACh and SNP, while it only affected the sensitivity and maximum relaxation to ACh in the male NC group (NC+Nic). There were no significant differences in the vasoreactivity of female mice exposed to e-cig or HFD. Finally, RNA-seq results suggested that e-cig-treated male mice had altered expression of genes related to endothelial and smooth muscle function and metabolism, particularly fatty acid metabolism, which was also significant with the addition of HFD.

Conclusion:
Collectively, our results suggest that acute e-cig exposure results in significant vascular dysfunction in male mice, which is worsened in HFD mice. The identification of genes dysregulated in mice exposed to e-cigs provides novel insights into vascular biology and could have a significant impact on our understanding of vascular complications associated with e-cig usage and provide insights into its contributions to obesity and diabetes.
Abstract 4134539: Hybrid Cardiomyocyte Targeting Peptide Down-regulates NF-κB Pathway in Human Cardiomyocytes
Authors: Wang Jingyu , Lopuszynski Jack , Sahagun Daniella , Zahid Maliha
Published: November 2024

Introduction:
Role of NF-κB driven inflammation leading to heart failure with preserved ejection fraction has received little attention. Our previous in vivo work with cardiac targeting peptide (CTP) in guinea pigs identified suppression of NF- κB pathway by CTP. In the current work we sought to further study the effects of a hybrid version of CTP (hCTP: amino acids at positions 3 and 11 substituted with D-amino acids) on TNF-α mediated NF-κB activation, as well as expression of its downstream inflammatory markers IL-1β and IL-8.

Methods:
Human cardiomyocytes (CMCs) were transfected using Lipofectamine 3000 with a reporter luciferase plasmid carrying an NF-κB promoter site upstream of the luciferase gene. Cells were treated with various concentrations of hCTP for 24 hours, followed by a TNF-α challenge (20ng/mL), addition of luciferin as substrate, and measurement of luminescence. Cell viability in response to above manipulations was assessed by FACS using live-dead stain. CMCs were treated as above, and cell culture supernatants analyzed for IL-8 levels using human ELISA kit. In another set of experiments, CMCs were transfected with NF-κB reporter plasmid, and after treatment for 24 hours with various concentrations of hCTP, incubated with 10nM angiotensin 2 (Ang2) and 100nM phenylephrine (PE) for 24hrs to assess levels of IL-1β in the cell culture media using an ELISA assay.

Results:
hCTP inhibited TNF-α mediated NF-κB activation with a dose-response curve, with maximum inhibition with hCTP seen at 10µM concentrations (p<0.001). Treatment with hCTP inhibited the TNF-α induced IL-8 secretion with significant decreases seen even at the 1µM dose. Similarly, secretion of IL-1β production by CMCs in response to Ang2/PE stimulation was suppressed by hCTP even at the lowest tested dose (1µM; p<0.5).

Conclusions:
Our data suggests that hCTP inhibited NF-κB pathway transcriptional activity in response to TNF-α stimulation in a dose-dependent fashion in human CMCs. Furthermore, treatment with hCTP inhibited TNF-α induced IL-8 and IL-1β secretion even at doses as low as 1µM. The ability of hCTP to efficiently targeting this inflammatory pathway suggests that it has therapeutic potential in the treatment of heart failure. Further in vivo studies are ongoing to test this hypothesis.
Abstract 4134560: Sex Differences in Repolarization Abnormalities Associated with Ventricular Arrhythmia in Mitral Valve Prolapse
Authors: Shaul Nathan , Cesmat Andrew , Chaudry Abdul , Gupta Suhani , Weickert Thelsa , Simpson Ross , Syed Faisal
Published: November 2024

Background:
Compared to men, women with mitral valve prolapse (MVP) are more likely to present with sudden death, and most women who die suddenly are premenopausal. Repolarization abnormalities are common in patients with MVP-attributed sudden death. However, differences in repolarization between men and women with MVP are not known.

Hypothesis:
Repolarization abnormalities are associated with ventricular arrhythmia and are more common in women than men with MVP.

Aims:
To investigate associations of ECG repolarization abnormalities with sex and ventricular arrhythmia in MVP.

Methods:
We reviewed 12-lead ECGs from 272 adults with MVP for T-wave inversion, ST segment elevation, ST depression, QTc and QT dispersion. Patients were excluded if they had prior MI, coronary artery disease, mitral valve surgery, moderate or severe LVH, heart failure, reduced left ventricular ejection fraction, atrial fibrillation or QRS duration >120ms. Transthoracic echocardiograms were reviewed for mitral regurgitation, mitral annular disjunction, bi-leaflet or myxomatous MVP. Ambulatory ECGs (n=94) were assessed for NSVT or PVCs (> 1% burden) and ECGs for >1 PVC on any 10 second tracing. Associations were evaluated using Fisher’s exact test, Wilcoxon rank-sum test or multiple linear regression.

Results:
Among 272 patients, median (IQR) age was 58 (47-67) years, 162 (59.6%) were women, 46 (16.9%) were African American, and 34 (12.5%) had frequent ventricular ectopy. Women and men had similar rates of NSVT (15/66 [22.7%] vs 4/28 [14.3%], p=0.41) and frequent ventricular ectopy (25/162 [15.4%] vs 9/110 [8.1%], p=0.093). The QTc was longer in women (433 [417, 446] vs 423 [406, 442] ms, p=0.023) and in those with NSVT (437 [421, 444] vs 421 [405, 436] ms, p=0.028), but not in those with ventricular ectopy (437 [420, 445] vs 428 [410, 444] ms, p=0.15). There was a trend towards increased QTc in patients with mitral annular disjunction (433 [418, 454] vs 429 [408, 444] ms, p=0.054) and myxomatous MVP (434 [414, 450] vs 427 [408, 444] ms, p=0.076). Female sex was the only independent predictor of QTc (R
2
=0.14, p=0.0032).

Conclusion:
Among patients with mitral valve prolapse, women have longer QT interval than men, and longer QT interval is associated with nonsustained ventricular tachycardia. Subtle or dynamic delay in repolarization may promote malignant ventricular arrhythmias in women. Understanding these relationships may help identify patients at risk for sudden death.
Abstract 4134569: Palliative care needs assessment by integrated palliative care outcome scale in hospitalized heart failure patients: an observational study
Authors: Hien Do Thi , Quyen Nguyen Quy , Ha Le Thanh , Hong Nga Nguyen Thi , Phuong To Lan , Hai Nguyen Thanh , Nghia Doan Van , Trang Do Thi , Kieu Ly Nguyen Thi , Son Pham Truong , Hinh Nguyen Van
Published: November 2024

Background and purpose:
Patients with heart failure (HF) have a high burden of palliative care needs (PCN) and a worse prognosis that is not lower than cancer. The Integrated Palliative Care Outcome Scale (IPOS) is a scale that evaluates PCN in illness patients, mostly in cancer.

Purpose:
To evaluate the PCN in hospitalized heart failure patients by IPOS and its relation with patients’ characteristics and mortality.

Methodology:
A cross-sectional study was conducted on 160 HF hospitalized patients in Vietnam, who were evaluated by IPOS, including questions using a 5-point Likert scale (0 [best]–4 [worst] points) about physical symptoms (10 items), emotional symptoms (4 items), and communication and practical issues (3 items). Patients were determined to have PCN if having ≥ two items with 4 points or ≥ 3 items with ≥ 3 points.

Results and discussions:
Mean age: 69,57 ± 11,95 years, male: 68.75%, mean LVEF: 44.19 ±16.11%, and NT-proBNP level: 9107.3 ± 30459.1ng/L, the percentage of patients with PCN was 59.38%. The majority of patients had moderate levels (2 points) of dyspnea (38.13%), weakness (35.0%), and low levels (0 or 1 point) of other physical symptoms. Moderate levels (2 points) were the most common in the patient’s anxiety (43.13%) and family anxiety (51.25%), feeling at peace (40.0%), sharing feelings (55.0%), enough information (45.0%), and practical issue (45.0%). Having PCN was significantly correlated to the duration of heart failure, eGFR, and usage of intravenous medication but not related to heart failure severity (NYHA class, LVEF, NT-ProBNP level) and other characteristics (age, gender, residency, educational levels, occupation). Having PCN was independently associated with higher all-cause mortality after discharge with follow-up for one year (P = 0.037).

Conclusions:
Hospitalized patients with HF had multi-dimensional symptom burdens in moderate levels. PCN was not related to HF severity but correlated to duration of heart failure, eGFR, and usage of intravenous medication. Having PCN was independently associated with mortality after discharge.
Abstract 4134590: Procedural Related Major Adverse Events of Cardiac Catheterization in Pediatric Patients with Cardiomyopathy: Insights from IMPACT Registry
Authors: Aldawsari Khalifah , kennedy kevin , MARTINEZ ALEJANDRO
Published: November 2024

Background:
Despite the role of cardiac catheterization for hemodynamic assessment and endomyocardial biopsy (EMB) in children with cardiomyopathy, data on procedure-related major adverse events (MAE) in this population is lacking. We aim to describe the rate of MAE in children with cardiomyopathy undergoing cardiac catheterization. Our secondary objective is to compare the rate of MAE among patient subsets within this population.

Hypothesis:
We hypothesize that the rate of MAE will vary among cardiomyopathy types and that EMB will be associated with an increased rate of MAE.

Methods:
We included patients with cardiomyopathy from the National Cardiovascular Data Registry Improving Pediatric and Adult Congenital Treatment (IMPACT) who were 18 years or younger and had cardiac catheterization from April 2016 to June 2023. We collected demographic, pre-procedural, procedural, and outcome-related variables. We performed univariate and multivariate analyses to identify variables independently associated with MAE.

Results:
A total of 15,656 procedures were evaluated, with a median age of 11 years; 50.3% were females. Dilated cardiomyopathy (DCM) was the most prevalent cardiomyopathy in 68%, followed by restrictive cardiomyopathy (RCM) in 14% and hypertrophic cardiomyopathy (HCM) in 9%. MAE was present in 1.6%. The most common MAE was arrhythmia, representing 46% of MAE, followed by cardiac arrest and bleeding each 20%. EMB was associated with a lower rate of MAE in univariate analysis p<0.001. The association between a lower rate of MAE and EMB persisted in the multivariate model when those with heart transplant who had EMB were compared to those without heart transplant who did not have EMB p=0.001. The multivariate analysis also revealed that age less than a year, HCM compared to DCM, history of heart failure, pre-procedural inotropic support, and non-elective procedure were associated with increased rate of MAE. The overall mortality rate was 1.66%. The leading cause of mortality was heart failure in 51% of deceased patients. MAE was associated with an increased mortality rate of 11% p<0.001.

Conclusion:
Cardiac catheterization is a safe procedure in pediatric patients with cardiomyopathy, with an overall MAE rate of 1.6%. Age of less than a year, HCM, history of heart failure, and prior inotropic support are associated with an increased rate of MAE. EMB was not associated with a higher rate of MAE. MAE occurrence is associated with a sevenfold increase in mortality rate.
Abstract 4134622: Hyperglycemia Induces Heterotaxy Syndrome by Lowering Intracellular pH
Authors: Matsuoka Ryohei , Kitajima Keiko , Ohga Shouichi , Meno Chikara
Published: November 2024

Background:
Pregestational diabetes is an established risk factor for congenital heart disease (CHD), including heterotaxy syndrome, which results from abnormal left-right (L-R) axis. However, the specific mechanism by which hyperglycemia disturbs the L-R axis still remains unsolved. In addition, it is unknown how a variety of heterotaxy is provoked by pregestational diabetes.

Methods:
We conducted whole-mount in situ hybridization, reporter analysis and RNA-seq in mouse embryos of streptozotocin-induced diabetic dams and
Wnt3a
–/–
embryos. Additionally, the effect of high-glucose conditions on intracellular pH (pH
i
) was investigated. We also examined the influence of maternal vitamin A intake on L-R axis formation in embryos of diabetic dams.

Results:
We observed various patterns of
Pitx2
expression in embryos of diabetic dams, indicating disrupted L-R axis. The initial step of L-R axis formation was impaired, with
Nodal
expression, which induces
Nodal
-
Pitx2
cascade in the lateral plate mesoderm, being regressed in the node. Consistent with the resemblance to the phenotype of
Wnt3a
–/–
embryos, canonical Wnt signaling was downregulated in embryos of diabetic dams. As the RNA-seq analysis suggested dysregulation of glycolysis, we assessed pH
i
to find that hyperglycemia lowers pH
i
in the primitive streak, leading to the regression of
Nodal
expression in the node. Furthermore, maternal vitamin A intake was found to increase the incidence and diversity of L-R axis defects, likely as a result of dysregulation of retinoic acid metabolism apparent in embryos of diabetic dams and
Wnt3a
–/–
embryos.

Conclusions:
Hyperglycemia downregulates canonical Wnt signaling by lowering pH
i
, which not only impairs L-R axis formation but also dysregulates retinoid metabolism. Consequently, embryos of diabetic dams become vulnerable to fluctuation of maternal vitamin A intake, resulting in diverse L-R axis defects. These findings provide insights into the etiology of CHD and suggest the importance of diet for prevention of heterotaxy during diabetic pregnancy.
Abstract 4134641: Door-in to door-out time and in-hospital mortality in patients with ST-elevation myocardial infarction
Authors: Nakashima Takahiro , Kiyoshige Eri , Ogata Soshiro , Cranford James , Ali Murtuza , Kindipan Ingrid , Tamis-Holland Jacqueline , Nishimura Kunihiro , Goyal Abhinav , Neumar Robert
Published: November 2024

Background:
Although current guidelines recommend achieving a door-in to door-out (DIDO) time within 30 minutes for 75% of patients with ST-elevation myocardial infarction (STEMI) who require interhospital transfer for primary percutaneous coronary intervention (PCI), disparities between guidelines and clinical performance persist.

Methods:
We analyzed the association between the DIDO time and in-hospital mortality using data from the Get With The Guidelines® – Coronary Artery Disease STEMI and NSTEMI Registry covering 232,935 admissions between the fourth quarter of 2019 and the third quarter of 2022. We determined the cut-off value of the DIDO time at which the odds of in-hospital mortality markedly increased by a likelihood ratio (LR) and an area under the curve (AUC) derived by generalized linear regression.

Results:
Of the 103,838 patients with STEMI, 23,865 (23%) required interhospital transfer. The median DIDO time was 63 (interquartile range 43–105) minutes and was within 30 minutes in 9% of cases. Generalized linear mixed models showed that a DIDO time delay of 5 minutes was significantly associated with higher in-hospital mortality (adjusted odds ratio [OR], 1.88; 95% confidence interval [CI], 1.56–2.27; p<0.001). The LR test and AUC showed that DIDO time cut-offs at 30, 42, 63, and 93 minutes were associated with increased in-hospital mortality. Compared with a reference DIDO time of within 30 minutes, the in-hospital mortality did not significantly differ for a DIDO time from 30 to 42 minutes (adjusted OR, 1.20; 95% CI, 0.83–1.73; p=0.340), but it was significantly higher for DIDO times from 42 to 63 minutes (adjusted OR, 1.48; 95% CI, 1.06–2.06; p=0.020), 63 to 93 minutes (adjusted OR, 1.89; 95% CI, 1.36–2.63; p<0.001), and over 93 minutes (adjusted OR, 2.85; 95% CI, 2.08–3.90; p<0.001).

Conclusion:
A delayed DIDO time was significantly associated with higher in-hospital mortality, particularly beyond 42 minutes.
Abstract 4134685: Cardiopulmonary Exercise Testing for Characterization and Prognostication in Hypertrophic Cardiomyopathy: A Meta-Analysis
Authors: Landsteiner Isabela , Masri Ahmad , Saberi Sara , maron Martin , McGinnis Shaina , Griskowitz Catharine , Newlands Chloe , Barriales-Villa Roberto , Owens Anjali , Lewis Gregory
Published: November 2024

Background:
Hypertrophic cardiomyopathy (HCM) carries substantial risk of adverse cardiac events. Consequently, detailed physiologic assessment and accurate risk stratification in HCM are of high clinical importance.

Aim:
To synthesize current evidence on the utility of cardiopulmonary exercise testing (CPET) for characterization and prognostication of HCM.

Methods:
PubMed, Embase, Scopus, and Web of Science were systematically searched for eligible studies from database inception to November 2023. Studies that had at least one CPET performed in HCM patients, with corresponding test data reported, were included. Abstracts with no full-text and studies focused on pediatric populations were excluded. The primary outcome was a composite endpoint of cardiovascular adverse events. Hazard ratios (HR) and 95% confidence interval (CI) from Cox proportional hazard model were meta-analyzed. This study was performed following the PRISMA guidelines and registered under PROSPERO (CRD42023487759).

Results:
Sixty full-length manuscripts focused on CPETs performed in HCM patients were included, comprising 12,914 patients. Despite male predominance (66%) and average age of 48 years, peak VO
2
was only 6.2 [95% CI, 6.0-6.4] metabolic equivalents (21.8 [20.9-22.6] mL/kg/min), consistent with significant functional limitation. In subanalyses, peak VO
2
was 18.9 [18.0-19.9] mL/kg/min in obstructive HCM and 22.5 [20.8-24.2] mL/kg/min in non-obstructive HCM. Compared to commonly used metrics such as NYHA Class, CPET markedly enhances sensitivity to detect impaired cardiac performance (
Figure
). This meta-analysis highlights several easily-derived CPET variables that consistently predict HCM prognosis. An increase of 1 mL/kg/min in peak VO
2
was associated with a lower HR of 0.83 [0.76-0.90] for adverse cardiac events, while a 1 unit increase in the VE/VCO
2
slope was associated with a higher HR of 1.12 [1.03-1.23]. Abnormal blood pressure response to exercise conferred a 2.5-fold [2.0-3.1] increase in adverse events.

Conclusion:
CPET is a valuable objective method for multi-dimensional physiologic assessment and prognostication in HCM. With further standardization, CPET is well suited for more widespread clinical utilization in HCM patients.
Abstract 4134692: In-Hospital Mortality Rate and Predictors of 30-Day Readmission in Cancer Patients with MI Undergoing PCI -A Cross Sectional Study From Nationwide Readmission Database
Authors: Aryal Badri , Gomez Valencia Javier , Oredipe Omotola , Sueldo, MD Alexandra , Soon-Shiong Raquel , Yilmaz Mahir
Published: November 2024

Background and objectives:
Data regarding readmission rates and predictors of readmission in cancer patients undergoing PCI are sparce. With the increasing survival rates and prevalence of cardiovascular complications in cancer patients, understanding the patterns and predictors of readmission in this population is paramount for optimizing their outcomes. Cancer patients pose unique clinical challenges due to their combined prothrombotic state and propensity for bleeding. We attempted to identify factors associated with readmission in cancer patients.

Methods:
We utilized the Nationwide Readmission Database from 2016 to 2020 and included patients more than 18 years of age with primary diagnosis of myocardial infarction(MI) who underwent percutaneous coronary intervention(PCI) and have a preexisting diagnosis of cancer. We used International Classification of Disease, Tenth Revision, Clinical Modification (ICD10 CM) codes to define MI, PCI, and cancer. The primary outcome was the 30-day readmission rate, and secondary outcomes were mortality rates, predictors of readmission, and common causes of readmission. The independent predictors of readmission were analyzed using cox regression analysis.

Results:
Of the 52,307 cancer patients who underwent PCI, 7,767 were readmitted within a 30-day period. The readmission rate for these patients was 15.70%. The mortality rate was 6.05% for index admission and 6.80% for readmitted cases. Among the readmitted patients in the strongest independent predictor for readmission were leaving against medical advice(AMA), anemia, congestive heart failure, and discharge to a skilled nursing facility or home health. Common causes of readmission within this time included hypertensive heart disease with concomitant CKD stage I-IV and heart failure (6.21%), sepsis (6.12%), NSTEMI (5.60%), hypertensive heart disease with concomitant heart failure (4.62%) and acute kidney injury (1.98%).

Conclusions:
Thirty-day readmission rate was 15.70%. Independent predictors of readmission were anemia, diabetes mellitus, congestive heart failure, malnutrition, peripheral artery disease, leaving against medical advice, and discharge to facility. Most common cause of readmission was hypertensive heart and kidney disease with heart failure, which comprised 6.21%.
Abstract 4134768: Geographic, Gender,&Racial Trends in Mortality Due to Heart Failure in Coronary Artery Disease Among Adults Aged 65 and Older in the United States, 1999-2020: A CDC WONDER Database Analysis
Authors: Naveed Muhammad Abdullah , Muhammad Omer Rehan , Azeem Bazil , Neppala Sivaram , Iqbal Rabia , Ali Ahilla , Chigurupati Himaja Dutt , Almas Talal , Sattar Yasar
Published: November 2024

Backgrounds:
Heart failure (HF) associated with coronary artery disease (CAD) is a significant contributor to mortality in the elderly population of the United States. This study examines trends in HF in CAD-related mortality among adults aged 65 and older, focusing on geographic, gender, and racial/ethnic disparities from 1999 to 2020.

Methods:
A retrospective analysis was performed using the CDC WONDER database death certificates from 1999 to 2020. Age-adjusted mortality rates (AAMRs), annual percent change (APC), and average annual percentage change (AAPC) were calculated per 100,000 persons, stratified by year, sex, race/ethnicity, and geographical region.

Results:
Between 1999 and 2020, there were 6,571,263 deaths attributed to coronary artery disease (CAD) and 6,135,540 deaths related to Heart Failure (HF) in the US. Among adults aged 65 and older, HF in CAD caused 1,597,451 deaths, with 37.1% occurring in medical facilities and 30.3% in nursing homes. The AAMRs for HF in CAD decreased from 241.7 in 1999 to 156.2 in 2020 (AAPC: -2.23, p < 0.000001). This reduction was significant from 1999 to 2014, followed by a slight increase from 2014 to 2020. Men consistently had higher AAMRs than women (227.4 vs. 137.1), with women experiencing a more significant decline in rates (AAPC: -3.23, p < 0.000001). Racial disparities revealed the highest AAMRs among Whites (183.0), followed by American Indians/Alaska Natives (153.7), Blacks (134.6), Hispanics (123.7), and Asians/Pacific Islanders (81.6). The most significant reductions were observed in Hispanics (AAPC: -2.68, p < 0.000001). Geographically, AAMRs varied, ranging from 92.1 in Hawaii to 257.3 in West Virginia, with the Midwest showing the highest mortality (191.0). Nonmetropolitan areas exhibited higher AAMRs than metropolitan areas (202.6 vs. 166.1), although both showed moderate declines over time, more pronounced in urban areas (AAPC: -2.41, p < 0.000001).

Conclusion:
The study uncovers notable variances in HF in CAD-related mortality among elderly individuals in the United States based on race, gender, and geographic location. While the decrease in AAMRs from 1999 to 2014 indicates progress in cardiovascular care, the subsequent rise from 2014 to 2020 and enduring disparities call for specific public health measures to tackle these inequalities.
Abstract 4134792: SIRTUIN5 Modulates Na
+
/Ca
2+
Handling Via Oxidative Stress Dependent Manner In Mouse Heart
Authors: Choi Hannah , Chen Biyi , Song Long-Sheng , Lombard David , Yoon Jin-Young , London Barry
Published: November 2024

Background:
The cardiac Na
+
channel Na
V
1.5 (encoded by
SCN5A
) governs cardiac inward Na
+
current (I
Na
) and the fast upstroke and plateau phases of the cardiac action potential. Mutations in Na
V
1.5 can cause acquired or inherited arrhythmias and conduction diseases, including ~20% of cases of Brugada Syndrome (BrS). Changes in I
Na
can impact Ca
2+
handling and cardiac excitation-contraction coupling. We have previously shown that SIRT1-mediated deacetylation of Na
V
1.5 increased I
Na
. Recently, potential mutations (including P114T) in SIRT5, another NAD
+
-dependent deACYLase in the Sirtuin family localized to mitochondria, were identified in small families with BrS.

Hypothesis:
Sirt5 dysfunction evokes arrhythmias via Na
+
and Ca
2+
mishandling in an oxidative stress-dependent manner in mouse hearts.

Aims:
To explore the potential role of SIRT5 in BrS using heterologous expression systems and homozygous P114T-Sirt5 knock-in (P114T-KI) mice.

Methods:
Protein expression and physical interactions were detected by immunoprecipitation and immunoblot. The effects of SIRT5 on Na
+
current was measured using patch clamp in HEK cells and mouse cardiac myocytes. Confocal microscopy was used to measure reactive oxygen species (ROS) and for Ca
2+
imaging.

Results:
Both WT and P114T-SIRT5 co-immunoprecipitate with Na
V
1.5, but WT increased peak I
Na
in HEK cells while P114T did not (Fig A,B). Live-cell staining using DCFDA or mitoSOX showed that P114T-KI hearts had increased basal ROS and were more sensitive to oxidative stress induced by H
2
O
2
than WT littermates. P114T-KI hearts had increased Na
+
/Ca
2+
exchange protein 1 (NCX1) expression, and Langendorff-perfused hearts displayed abnormal Ca
2+
handling and arrhythmias (Fig C). Notably, treatment with the mitochondrial ROS scavenger mitotempo mitigated the aberrant Ca
2+
handling and arrhythmias.

Conclusion:
These findings suggest that the P114T-SIRT5 causes abnormal Na
+
and Ca
2+
handling and arrhythmias in a ROS-dependent manner, highlighting potential mechanisms underlying BrS. This finding may pave the way for the use of SIRT5 or its activators as novel anti-arrhythmic therapies in the future.
Abstract 4134825: Diabetic ketoacidosis and hyperglycemic hyperosmolar state outcomes in diabetes patients hospitalized with ST-elevation myocardial infarction
Authors: Almutairi Turki , Dargham Soha , Jayyousi Amin , Al Suwaidi Jassim , Abi Khalil Charbel
Published: November 2024

Background:
Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are acute life-threatening hyperglycemia conditions.

Aims:
We aimed to assess their impact on type 2 diabetes patients admitted for ST-elevation myocardial infarction (STEMI).

Methods:
Data was extracted from the National Readmission Database (2016-2019). The primary endpoint was in-hospital mortality. Secondary endpoints included in-hospital arrhythmias, cardiogenic shock, and 30-day readmission and mortality.

Results:
A total of 112,829 patients hospitalized for STEMI with a concomitant diagnosis of type 2 diabetes were hospitalized between 2016 and 2019, of whom 112,799 were included in our analysis after the exclusion of patients with missing data (
Figure 1
). Of those patients, 330 had a diagnosis of DKA, and 292 had a diagnosis of HHS. After 30 days from the initial hospitalization, 118 (35.7%) out of the initial DKA group, 102 (34.9%) out of the initial HHS group, and 26,523 (23.6%) of STEMI patients with diabetes were readmitted. The presence of DKA increased the odds of in-hospital mortality and cardiogenic shock by almost 2-fold (aOR = 2.30 [1.70-3.12], 2.055 [1.602-2.637], respectively) and renal failure by almost 5-fold (aOR = 5.175 [4.090-6.546]) (
Table 1
). HHS was also associated with higher odds of mortality, acute renal failure, and cardiogenic shock. Within 30 days of initial admission, DKA and HHS increased the risk of readmission (aOR= 1.815 [1.449-2.75], 1.751 [1.376 - 2.228], respectively), but not mortality. Cardiovascular disease was the most common etiology of readmission in all patients (
Figure 2)
. The prevalence of non-STEMI was the highest in DKA patients (22.9%), and the prevalence of STEMI was the highest in the HHS group (37.9%).

Conclusion:
The presence of diabetic ketoacidosis or hyperglycemic hyperosmolar states is associated with higher odds of mortality, renal failure, cardiogenic shock, and 30-day readmission in STEMI patients with type 2 diabetes.
Abstract 4134837: Checkpoint Kinase 1 Attenuates Myocardial Ischemia-Reperfusion Injury Through Maintaining SIRT1-Dependent Mitochondrial Homeostasis
Authors: yang tongtong , Zhou liu-hua , shan tiankai , Wang Hao , Wang Liansheng
Published: November 2024

Background:
Mitochondrial dysfunction is linked to myocardial ischemia-reperfusion (I/R) injury. Checkpoint kinase 1 (CHK1) could facilitate cardiomyocyte proliferation and cardiac repair post myocardial infarction, however, its role on mitochondrial function in I/R injury remains unknown.

Research Questions:
The purpose of this study is to explore the potential effects and mechanisms of CHK1 on mitochondrial homeostasis during myocardial I/R injury.

Methods:
To investigate the role of CHK1 on mitochondrial function following I/R injury, cardiomyocyte-specific knockout/knock-in mouse models were generated. Mass spectrometry-proteomics analysis and protein co-immunoprecipitation assays were conducted to dissect the molecular mechanism of CHK1. The interaction between CHK1 and SIRT1 was explored using truncated plasmids.

Results:
CHK1 was downregulated in myocardium post I/R and neonatal mouse cardiomyocytes (NMCMs) post oxygen-glucose deprivation/re-oxygenation (OGD/R).
In vivo
, CHK1 overexpression protected against myocardial I/R injury, while heterogenous CHK1 knockout exacerbated cardiomyopathy.
In vitro
, CHK1 inhibited OGD/R-induced cardiomyocyte apoptosis and bolstered cardiomyocyte survival. Mechanistically, CHK1 attenuated oxidative stress and preserved mitochondrial metabolism in cardiomyocytes under I/R. Moreover, disrupted mitochondrial homeostasis in I/R myocardium was restored by CHK1 through the promotion of mitochondrial biogenesis and mitophagy. Through mass spectrometry analysis following co-immunoprecipitation, SIRT1 was identified as a direct target of CHK1. The 266-390 domain of CHK1 interacted with the 160-583 domain of SIRT1. Importantly, CHK1 phosphorylated SIRT1 at Thr530 residue, thereby inhibiting SMURF2-mediated degradation of SIRT1. CHK1 Δ390 amino acids (aa) mutant functioned similarly to full-length CHK1 in scavenging ROS and maintaining mitochondrial dynamics. Consistently, cardiac-specific SIRT1 knockdown partially attenuated the protective role of CHK1 in I/R injury.

Conclusions:
Our findings revealed that CHK1 mitigates I/R injury and restores mitochondrial dynamics in cardiomyocytes through a SIRT1-dependent mechanism.
Abstract 4134841: A Diagnostic Pitfall: Subclavian Stenosis Mimicking Severe Aortic Stenosis on Echocardiography"
Authors: Ezaldin Shady , ABDELSALAM MAHMOUD , Elsayed Omar , Lee Marciano
Published: November 2024

Background:
Aortic stenosis (AS) is a common and serious valve disease in the elderly, often diagnosed using echocardiography. However, certain conditions can mimic AS, leading to diagnostic challenges. This case highlights the importance of a comprehensive vascular assessment in patients with atypical symptoms and echocardiographic findings suggestive of severe AS.

Case Presentation:
An 80-year-old female presented with progressive dizziness and double vision over the past few months. She reported a long-standing history of lower blood pressure in her right arm compared to her left. Her medical history was significant for HER2-positive intraductal breast cancer treated with neoadjuvant chemotherapy. An echocardiogram performed two months prior to presentation, using a Pedoff probe, indicated severe AS with a peak systolic velocity of 5.1 m/sec, a mean systolic gradient of 50 mm Hg, and an aortic valve area of 0.6 cm.

Investigations:
Given the discrepancy in blood pressure between her arms and the wide open aortic valve on the echo which dosen't corrleate with the doppler numbers, CTA neck and chest was performed, revealing a dense calcific plaque causing severe stenosis at the origin of the left subclavian artery. An angiogram confirmed >75% stenosis of the left subclavian artery, which was treated with angioplasty and stent placement, resulting in <10% residual stenosis.

Outcome:
Following the intervention, a repeat echocardiogram showed only mild calcification of the aortic valve with a mean gradient of 4 mm Hg, significantly lower than the previous findings.

Discussion:
This case underscores the potential for subclavian artery stenosis to mimic severe AS on echocardiography, particularly when using the Pedhoff probe. It highlights the need for clinicians to consider vascular anomalies in the differential diagnosis when echocardiographic doppler findings do not correlate with clinical symptoms or with the structural apperance of the valves.

Conclusion:
Comprehensive assessment and consideration of alternative diagnoses are crucial in patients with suspected severe AS, especially when using Doppler echocardiography. Awareness of the potential for subclavian artery stenosis to cause false-positive echocardiographic findings can prevent unnecessary interventions and guide appropriate management.