bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4140759: Clinical Outcomes Of SGLT2 Inhibitors In Patients Hospitalized With Acute Heart Failure: A Meta-analysis Of Randomized Control Trials
Authors: Gupta Soumya , Thakkar Aditya , Koh Won-joon , Choi James , Hart Hannah , Mahmood Kiran
Published: November 2024

Introduction:
Acute heart failure (AHF) presents challenges due to its poor prognosis and limited therapeutic options compared to chronic heart failure (CHF). The potential benefits of SGLT2 inhibitors in AHF patients are being explored, yet systematic evaluation is lacking. Our meta-analysis aims to bridge this gap by comparing the efficacy and safety of SGLT2 inhibitors versus placebo in AHF patients.

Research question:
Clinical Outcomes Of SGLT2 Inhibitors In Patients Hospitalized With Acute Heart Failure

Methods:
We searched Medline, Embase, and Cochrane databases for randomized controlled trials involving adult patients hospitalized with AHF, who received SGLT2 inhibitors. Our primary outcomes were all-cause mortality, heart failure events, and readmissions. The secondary outcomes were change in KCCQ-TSS (Kansas City Cardiomyopathy Questionnaire), weight, length of stay and NT-proBNP levels. Safety outcomes included hypotension, hypoglycemia, UTI, DKA, and acute renal failure. We used Review Manager 5.4 for statistical analysis, employing standardized mean difference (SMD) and risk ratio (RR) with 95% confidence intervals (CI).

Results:
Seven RCTs were included, involving a total of 2321 patients, with 49.5% receiving SGLT2 inhibitors. Patients receiving SGLT2 inhibitors showed a significant reduction in the risk of readmissions by 32% (RR = 0.68, p < 0.00001). They also showed a non-significant but reduced risk of all-cause mortality by 24% (RR = 0.76, p = 0.04), and heart failure events by 27% (RR = 0.63, p = 0.09).

With respect to the secondary outcomes, there was a significant reduction in KCCQ-TSS (SMD= -0.17; 95% CI: -0.26 to -0.08; p=0.004) and weight (SMD= -0.34; 95% CI: -0.55 to -0.13; p=0.002) in the intervention group as compared to the placebo group. This group was also associated with a non-significant but reduced length of stay (SMD= -0.01; 95% CI: -0.20 to -0.18; p=0.90) and NT-proBNP levels (SMD= -0.06; 95% CI: -0.29 to -0.17; p=0.61).

On analysis of the safety outcomes, there was a non significant difference in the risk of acute renal failure, UTI, and DKA.

Conclusion:
In patients with AHF, initiation of SGLT2 inhibitors showed a statistically significant reduction in heart failure rehospitalizations, improved weight-based diuretic efficiency, and KCCQ-TSS. These findings suggest that starting SGLT2 inhibitors in patients hospitalized for AHF is well tolerated and leads to clinical benefits.
Abstract 4140779: Short-term outcomes and coronary microvascular dysfunction after percutaneous coronary intervention in severely calcified lesions: A comparison between rotational atherectomy and intravascular lithotripsy.
Authors: Kusumoto Hirofumi , Shishikura Daisuke , Yamauchi Yohei , Sakane Kazushi , Morita Hideaki , Hoshiga Masaaki
Published: November 2024

Background:
Treatment of calcified coronary artery stenosis remains challenging and is associated with worse clinical outcomes. For successful PCI of calcified lesions, it is imperative to achieve sufficient plaque modification before stent implantation.

Aims:
The aims of the current study were to evaluate coronary microvascular dysfunction and short-term outcomes in heavy calcified coronary lesion underwent PCI with intravascular lithotripsy (IVL) versus rotational atherectomy (RA).

Methods:
We retrospectively analyzed 91 patients underwent PCI with severely calcified coronary stenosis treated with atherectomy devices. Of these, coronary microvascular function was assessed using temperature-sensor guidewire

(PressureWire X, Abott) in 40 patients (IVL: 21, RA: 19) before and after PCI. Procedural success including successful stent delivery with <30% residual angiographic stenosis and successful stent expansion, and post-procedural clinical outcomes (30 days in-hospital) including all cause death, non-fatal myocardial infarction (MI), MI and target vessel revascularization were also evaluated.

Results:
A total of 61 patients underwent calcium modification with RA and 30 with IVL. The mean age was 76.1 years and a high prevalence of diabetes (59%), chronic kidney disease (30%), and dialysis (13%). There were no significant differences in procedural success rate between two groups (93% for IVL vs. 82% for RA, p=0.20) (Table). The rate of procedural complication including flow-limiting dissection, perforation and slow flow phenomenon, was lower in IVL group (13% vs. 33%, p=0.04) and non-fatal MI was high likely observed in RA group compared to IVL group (36% vs. 3%, p<0.01).

From the physiological analysis, resting full-cycle ratio (RFR) and fractional flow reserve (FFR) were significantly improved after PCI in both groups. Index of microcirculatory resistance (IMR) after PCI was numerically lower in IVL group compared to RA group (14.5 vs. 29.9, p=0.07). Coronary fractional reserve (CFR) after PCI was significantly higher in IVL group (2.99 vs. 1.82, p=0.02) (figure).

Conclusion:
IVL and RA are both effective devices to treat severely calcified coronary stenosis with similar procedural success outcomes. However, IVL was associated with lower incidence of coronary microvascular dysfunction compared to RA, indicating that consideration on device selection would be required in high risk patients with severely calcified coronary disease.
Abstract 4140823: Differences Exist in Cardiovascular Death among Asian Heritage Groups Based on Nativity Status in the US: Analysis of 1999-2018 National Health Interview Survey
Authors: Ramesh Arshia , Benjasirisan Chitchanok , Lim Arum , Kruahong Suratsawadee , Chen Yuling , Ogungbe Bunmi , Turkson-Ocran Ruth-Alma , Commodore-Mensah Yvonne , Koirala Binu
Published: November 2024

Background:
Asians are the fastest-growing population in the United States (US). Cardiovascular disease (CVD) remains the leading cause of disability and death among persons of Asian heritage in the US. Certain groups of Asian heritage may be at disproportionately high risk of CVD and all-cause death.

Hypothesis:
We hypothesize that there is heterogeneity in CVD and all-cause death among disaggregated Asian heritage groups (Chinese, Filipino, and Asian Indian, and others) based on nativity status (US- vs Foreign-born).

Methods:
The study analyzed pooled data from the 1999-2018 National Health Interview Survey linked with the National Death Index. The outcomes were CVD death (disease of heart and cerebrovascular disease deaths, based on ICD-10) and all-cause death, in years, derived from the time of interview to the year of death or December 31, 2019 (last date of follow-up). Survey-weighted Cox regression models were used to explore differences in CVD and all-cause death among Asian heritage groups, controlling for covariates (age, sex, marital status, poverty-income ratio, and education).

Results:
The study included 37,104 Asian adults (21.8% Chinese, 33.5% Filipino, and 44.6% Asian Indians and others). Over a median follow-up of 11 years (Interquartile range: 7-15), there were 1.7 CVD deaths and 5.6 all-cause deaths per 1,000 person-years. The fully adjusted model revealed a 33% lower CVD death hazard among foreign-born Filipino adults (Hazard Ratio [HR]: 0.67; 95% Confidence Interval [CI]: 0.49–0.91) compared to their US-born counterparts. Similarly, for all-cause death, foreign-born Asian Indians exhibited a 40% lower hazard (HR: 0.60; 95% CI: 0.48-0.74), and Filipinos showed a 33% lower hazard (HR: 0.67; 95% CI: 0.51-0.88) when compared to their US-born counterparts.

Conclusion:
There was heterogeneity in CVD and all-cause death among Asian heritage groups. Overall, CVD and all-cause death were lower among foreign- than US-born adults specifically among Filipino and Asian Indian and others. These findings warrant the targeted implementation of evidence-based approaches to CVD prevention and promotion.
Abstract 4140883: Human iPSCs and Human iPSC-Endothelial cells Derived from PAD Patients and Healthy Donors Have Similar Characteristics and Potency: Implications for Autologous Cell Therapy in Peripheral Artery Disease
Authors: Bae Jung Yoon , Lee Shin-Jeong , Bae Seongho , Jung Cholomi , Jung Ji-Hyeon , Han Ji Woong , Park Sin-Hye , Kim Yonghak , Kim Jungwoo , Kim Hyun-Kyung , Lee Seung-Jun , Ko Young-Guk , Choi Donghoon , Kim Hyun Ok , Yoon Young-sup
Published: November 2024

Background:
Peripheral artery disease (PAD) can lead to amputation in advanced cases, making cell therapy using human induced pluripotent stem cells (hiPSCs) a promising therapeutic option. hiPSC-derived endothelial cells (hiPSC-ECs) have shown favorable effects in treating experimental ischemic cardiovascular disease. An autologous approach for PAD patients is preferable to avoid immunological reactions. However, it is yet unknown whether hiPSCs and hiPSC-ECs derived from PAD patients have similar characteristics and potency compared to those derived from healthy volunteers. Therefore, we explored whether there are significant differences in the characteristics and potency of hiPSCs and hiPSC-ECs between non-PAD donors and PAD patients.

Methods and Results:
We successfully generated hiPSCs from the blood of seven non-PAD donors and eight PAD patients. Both non-PAD and PAD-derived hiPSCs exhibited similar expression levels of pluripotency markers, as determined by qRT-PCR, flow cytometry, and immunostaining. All hiPSCs, regardless of the group, formed teratomas and showed normal karyotypes. RNA-seq analyses revealed similar gene expression profiles between the groups. We then differentiated hiPSCs into endothelial cells (ECs) in a clinically compatible manner. hiPSC-ECs derived from both non-PAD and PAD donors exhibited similar expression levels of EC markers at both the gene (qRT-PCR) and protein levels (immunostaining and flow cytometry). RNA-seq analyses showed no significant overall differences in gene expression profiles between the groups. In vitro nitric oxide assays and tubular structure formation assays demonstrated similar endothelial characteristics and function in hiPSC-ECs from both groups. When injected into the hindlimb muscle following induction of hindlimb ischemia, both groups showed similar perfusion recovery, limb salvage, and vessel-forming capacity. Engrafted hiPSC-ECs from both groups also exhibited similar angiogenic and vessel-forming capabilities.

Conclusions:
Our study demonstrated no significant differences in hiPSCs and hiPSC-ECs derived from non-PAD donors and PAD patients in terms of molecular and cell biological characteristics, therapeutic effects, and vessel-forming capability. Our study indicates that hiPSCs and hiPSC-ECs derived from PAD patients can serve as a novel platform for autologous cell therapy.
Abstract 4140907: Trends and Disparities of Ischemic Stroke–Related Mortality Among the Young Adults in the United States from 1999-2020
Authors: Chia Jia Ee , Ang Song Peng , Mukherjee Debabrata
Published: November 2024

Background:
Stroke remains a leading cause of mortality and morbidity globally, with a notably increasing incidence among young adults. Despite this trend, detailed insights into mortality trends specifically for young adults suffering from ischemic stroke (IS) are sparse.

Methods:
Leveraging data from the CDC's Wide-ranging Online Data for Epidemiologic Research database, we identified individuals aged 15 to 44 with IS-related mortality. We calculated age-adjusted mortality rates (AAMR) per million persons and analyzed annual percent changes. Subgroup analysis was conducted to examine differences by age, gender, race, and geographic region.

Results:
From 1999 to 2020, there were 9,906 ischemic stroke-related deaths among young adults. The overall AAMR for ischemic stroke-related mortality increased from 4.19 in 1999 to 5.20 in 2020 (p-trend<0.001). Notably, men exhibited a higher AAMR (3.91 [95% CI, 3.81-4.01]) compared to women (3.19 [95% CI, 3.10-3.29]). Mortality rates peaked in the 35-44 year age group. Among racial groups, Black or African American individuals had the highest AAMR at 5.92 ([95% CI, 5.68-6.15]), significantly higher than White individuals (AAMR 3.25 [95% CI, 3.17-3.33]). Geographically, the Southern region of the U.S. recorded the highest AAMR (4.10 [95% CI, 3.98-4.23]).

Conclusion:
Our analysis reveals a concerning increase in ischemic stroke–related mortality among young adults in the United States. The data highlight significant disparities, with notably higher mortality rates among men and Black or African American individuals. Furthermore, pronounced geographical variations in mortality rates emphasize the necessity for targeted, region-specific public health interventions to address these disparities effectively.
Abstract 4140966: Outpatient Cardiology Performance Metric Achievement by Clinicians in the Veteran Affairs Health Care System
Authors: Chow Christine , Salahuddin Taufiq , Chen Claire , Gunzburger Elise , HESS PAUL , Doll Jacob
Published: November 2024

Introduction:
Veterans Affairs (VA) facilities evaluate cardiology clinicians using three performance measures for outpatient care: anticoagulation for atrial fibrillation or atrial flutter (AF) with elevated stroke risk, statin therapy for coronary artery disease (CAD), and renin-angiotensin-aldosterone system (RAAS) inhibition for heart failure (HF). We sought to assess these metrics and their differences by clinician characteristics using VA health record data.

Methods:
We assessed AF, CAD, and HF performance measures for cardiology clinicians with at least 50 annual outpatient encounters from 2017-2023 in VA. A clinician-patient relationship was defined as ≥2 encounters within 1 year or ≥3 encounters within 3 years. Performance measure achievement was calculated separately for each clinician as well as an overall average. If more than one encounter occurred per year for a clinician-patient dyad, one was chosen at random for evaluation. Clinician performance distributions were represented as histograms, and differences in unadjusted performance by clinician training status and gender were assessed using Welch two sample t-tests.

Results:
Of 456,071 unique cardiology encounters, 179,476 included AF with elevated stroke risk, 313,603 included CAD, and 225,476 included HF with EF ≤40%. There were 1,046 cardiology providers including 53% physicians and 52% women. Overall mean performance measure achievement was 87.7%. Mean performance scores for AF, CAD, and HF were 86.3%, 94.2%, and 78.9% respectively, and distributions are shown in the
Figure
. There was a modest difference in unadjusted overall performance between physicians and non-physician providers (88.0 vs. 87.2%, p = 0.005) and no difference between female and male clinicians (87.5% vs. 87.8%, p = 0.4)

Conclusion:
There was high achievement of three established VA outpatient cardiology performance measures with minimal differences by clinician training or gender. This may represent a ceiling effect. However, significant variation remained at the clinician level, indicating potential opportunities for quality improvement even for these well-established treatments.
Abstract 4140979: CD34
+
Cells Contributed to Cardiac Fibrosis Are Regulated by Hyperlipidemia
Authors: Guo Yan , Du Luping , Wang Xuyang , Guo Xiaogang , Xu Qingbo
Published: November 2024

Background:
Lipid metabolic alterations are emerging as significant mechanisms in the prognosis of cardiac remodeling induced by hypertension and could impact the therapies for cardiac fibrosis. The fatty acid transport/oxidation gene FABP4 acts as a metabolic and inflammation regulator, whose inhibition can attenuate kidney and renal interstitial fibrosis. However, its role in the heart remains unclear. Our study aimed to evaluate the density of FABP4 in patients and mouse model, and its association with cardiac fibrosis.

Methods and Results:
Single cell RNA sequencing of the heart and enriched Cd34-tdTomato
+
lineage cells in human and a murine model treated with angiotensin II were performed. Through the analysis of single-cell transcriptomes extracted from mouse hearts and human hearts tissues, we explored the transcriptomic landscape throughout cardiac fibrosis and revealed dysregulation of cardiac fibrosis, fatty acid transport/oxidation, and PPARγ signaling in the failing heart. We identified in which the FABP4
+
fibroblasts were increased in diseased tissues accompanied by the accumulation of lipid droplets and cardiac fibrosis. Using pseudotime analysis, inducible lineage tracing and bone marrow transplantation models, our study showed that hypertension can expedite the differentiation of non-bone marrow-derived CD34
+
cells into FABP4
+
fibroblasts, leading to lipid accumulation and cardiac fibrosis. Furthermore, the PPARγ/Akt/Gsk3β pathway plays a critical role in orchestrating the differentiation process. Interestingly, both in vitro and in vivo, partial depletion of CD34
+
cells using diphtheria toxin or pioglitazone treatment resulted in a notable reduction of FABP4
+
fibroblasts and triglyceride in heart, along with an improvement in cardiac function through the PPARγ pathway. Additionally, GW9662, a selective antagonist of PPARγ, markedly reduced cell lipotoxicity and cardiac fibrosis.

Conclusions:
Collectively, our study provides valuable insights into the cellular landscape of the fibrotic heart with hypertension, indicating that the differentiation of non-bone marrow-derived CD34
+
cells into FABP4
+
fibroblasts accelerates the lipid accumulation and progression of cardiac fibrosis via PPARγ pathway.
Abstract 4140993: Time-Restricted Feeding Alleviates Cardiac Aging through Gut Microbiota
Authors: Tai Shi , Fu Liyao , Yang Rukai , Zhou Shenghua
Published: November 2024

Background:
Time-restricted feeding (TRF) is an effective strategy for anti-aging management yet its prophylactic/therapeutic applicability against cardiac aging is unknown.

Methods:
To assess the effects of TRF on cardiac aging, male mice were randomized into the normal diet+ad libitum feeding (N-ALF), normal diet+TRF (N-TRF), high-fat diet+ALF (H-ALF), high-fat diet+TRF (H-TRF). Metagenomic sequencing was used to investigate the diversity, composition, and evolution of the gut microbiota. The metabolomics was employed to investigate the impact of TRF on the metabolic profile of feces. Using fecal microbiota transplantation, TRF has been validated to delay cardiac aging by optimizing gut microbial composition and function.

Results:
Compared to the H-ALF group, the H-TRF group showed that the expression of senescence markers p53 and p21 was reduced. In addition, the myocardial interstitial collagen deposition and the expression of collagen I and III were reduced by TRF. Moreover, TRF reduced left ventricular posterior wall dimensions at end-diastole, interventricular septal thickness at end-diastole, and myocardial diastolic function index E/e' in mice. These suggested that TRF delays high-fat diet-induced cardiac aging. Compared with the H-ALF group, the TRF group exhibited an increase in the alpha diversity of gut microbiota. At the phylum level, the abundance of the Bacteroides was increased by TRF. At the genus level, the abundance of Bacteroides, Parabacteroides, and Akkermansia was increased by TRF. There were 11 characteristic strains in the H-TRF group, six of these strains are closely related to the production of short-chain fatty acids (SCFAs). Function prediction of the differential genes showed an increase in the SCFAs pathway in the H-TRF. LC-MS profiling of feces showed that TRF can reduce the levels of l-tyrosine, l-tryptophan, phenylalanine, valine, indoxyl-sulfate, cholesterol-sulfate, and tetradecanedioic acid in the intestines from high-fat diet mice. TRF increased the levels of 16-oxo-heptadecanoic acid, propionic acid, butyric acid, 2-methylpropionic acid, acetoacetate, succinate, and acetoacetyl-CoA. Using the mice with HFD, those that received gut microbiota from H-TRF showed decreased levels of cardiac senescence markers. It was suggested that gut microbiota plays a crucial role in TRF improving cardiac aging.

Conclusions:
TRF improves high-fat diet-induced cardiac aging by optimizing the composition and function of gut microbiota.
Abstract 4140995: Ultrasonic Vaping Devices Heat at Lower Temperatures than Coiled E-Cigarettes, but can Cause Comparable Levels of Cardiac Fibrosis
Authors: Goyal Natasha , Wang Ping , Wang Zhong-Min , Kavuri Maansa , Derakhshandeh Ronak , Kumagai Kazukiyo , Springer Matthew
Published: November 2024

Background:
Coil-less ultrasonic vaping devices like Surge use an ultrasonic chip that vibrates at several million Hz, aerosolizing the e-liquid. They are advertised as emitting significantly lower levels of toxins than coiled e-cigs by heating to lower temperatures that produce fewer chemical breakdown products. We tested the hypothesis that ultrasonic e-cigs cause less adverse cardiac effects than coiled e-cigs.

Methods:
We exposed 3 groups of conscious Sprague Dawley rats (n=8/group) to aerosol from JUUL (Virginia Tobacco 5% nicotine), Surge (Rich Tobacco 18 mg/ml nicotine), or air. Pulsatile exposure consisted of 10 consecutive cycles, each consisting of 2s exposure to aerosol followed by 28s of clean air, over 5 min, for 9 weeks using a Gram Research universal vaping machine. Hearts were then isolated, sectioned, and stained for left and right ventricular fibrosis with Sirius Red. Temperature profiles for the Surge ultrasonic vaping device were obtained at the California Department of Public Health (CDPH) via a single point thermocouple probe.

Results:
Temperature profiles of Surge during one session of aerosol production (with airflow) showed temperatures not exceeding 132 degrees Celsius. (We previously reported that the USONICIG Zip ultrasonic vaping device with air flow heated to ~77 degrees Celsius; reported temperatures of coiled e-cigs are up to 300 degrees Celsius.) Fibrosis was significantly increased in the JUUL group compared to air (p=0.04). Mean fibrosis in the Surge group was comparable to that in the JUUL group (p=0.84) and was higher than air fibrosis but did not reach significance (p=0.15), potentially due to high variability of Surge values.

Conclusion:
Temperature profiles of ultrasonic vaping devices are substantially lower than those of coiled vaping devices, with Surge being warmer than USONICIG Zip under airflow conditions. Despite lower temperatures, ultrasonic vaping devices cause a comparable level of cardiac fibrosis to conventional coiled vaping devices. Therefore, Surge does not avoid the increase in cardiac fibrosis that we have reported for coiled e-cigs and for smoke from tobacco or marijuana.
Abstract 4141027: Platelet Activation in Patients with Peripheral Artery Disease From 43 Sites: Assessment of Samples Transported by Overnight Mail
Authors: Stubblefield William , Sullivan Alexander , Amin Taneem , Boutaud Olivier , Cahill Katherine , Flaherty David , Matlock Brittany , Berger Jeffrey , Beckman Joshua
Published: November 2024

Background:
Platelet activation plays a key role in peripheral artery disease (PAD), but the relevant platelet activation mechanism in chronic limb threatening ischemia remains unclear. Moreover, multi-center study of platelet activation remains difficult due to methodologic limitations. We report the feasibility of a novel method to measure platelet activation using samples sent via overnight mail. The primary objective was to report baseline markers of platelet activation from samples sent by overnight mail compared to an age-matched population recruited locally without known atherosclerosis.

Methods:
Peripheral venous blood was drawn from 190 participants with severe peripheral artery disease at 43 sites in the BEST-CLI (Best Endovascular Versus Best Surgical Therapy in Patients with Chronic Limb Ischemia) Trial and shipped by Federal Express cold pack from study site locations within the continental United States to Vanderbilt University Medical Center. Fifty-six volunteers with and without diabetes were recruited locally as time and age-matched control subjects. Samples were collected using a platelet activation inhibitor. Thromboxane B2, dilysyl-malondialdehyde (MDA), p-selectin, WEDE 15, and SPAN 12 as markers of platelet activation were measured using liquid chromatography with tandem mass spectrometry and flow cytometry.

Results:
Compared with control subjects, patients from the BEST-CLI trial were more likely to be male (72.6% vs 51.8%, p<0.01), have prior atherosclerotic cardiovascular disease (22.1% vs 0%, p<0.01), and be prescribed aspirin (69.4% vs 35.7%, p<0.01) or clopidogrel (20.0% vs 0%, p<0.01). Thromboxane B2 (0.5 vs 2.9 ng/mL, p<0.01) and dilysyl-MDA (4.7 vs 9.7 ng/mg, p<0.01) were significantly higher in BEST-CLI patients than control subjects while p-selectin (592.0 vs 420.5 MFI, p<0.01) was lower. Levels of thromboxane B2 (figure 1A) and dilysyl-MDA (figure 1B) varied significantly and as expected across the range of antithrombotic prescription (p<0.01).

Conclusions:
Measurement of platelet activation after sample shipment on cold pack is feasible and yields reliable results that match expected clinical values.
Abstract 4141028: Predicting survival after percutaneous ventricular assist device for patients with cardiogenic shock: J-PVAD risk score
Authors: Kondo Toru , Yoshizumi Tomo , Morimoto Ryota , Imaizumi Takahiro , kazama shingo , Hiraiwa Hiroaki , OKUMURA TAKAHIRO , Murohara Toyoaki , Masato Mutsuga
Published: November 2024

Background:
Cardiogenic shock (CS) is a lethal condition and mechanical circulatory support is indicated if refractory to drug treatment. A recent report showed using Impella with standard care led to a lower risk of death in patients with acute myocardial infarction and CS. This finding may increase the clinical use of Impella, but prognostic models for patients after Impella are lacking.

Aims:
To identify factors that predict in-hospital mortality in CS requiring Impella and to develop a new prognostic model.

Methods:
We used the dataset of the Japanese registry for Percutaneous Ventricular Assist Device (J-PVAD), which included all the cases treated with Impella in Japan. Two-thirds of the patients treated with Impella due to CS were randomly assigned to a derivation cohort, and the other third was reserved as a validation cohort. Using the derivation cohort, a backward stepwise logistic regression model was built to identify the factor associated with in-hospital mortality.

Results:
Of the total 1,715 patients in the derivation cohort, 989 patients were discharged alive and 726 patients (42.3%) died during hospitalization. From 28 variables available in the J-PVAD registry, 12 variables were independently associated with in-hospital mortality and applied for a component of the risk model; age, sex, body mass index, etiology of fulminant myocarditis, cardiac arrest in hospital, extracorporeal membrane oxygenation use, mean arterial pressure, lactate level, lactate dehydrogenase level, total bilirubin level, creatinine level, and albumin level (Table 1). The J-PVAD risk score was created by assigning scores to these components based on the coefficients (Table 1). An Example of predicted in-hospital mortality according to the J-PVAD risk score is shown in Table 2. The area under the receiver operating characteristics curve (AUC) of the J-PVAD risk score was 0.76 (95% confidence interval [CI] 0.73–0.78). The comparison of predicted and observed in-hospital mortality according to the 7th quantiles by the J-PVAD risk score showed good calibration (Figure A). In the validation cohort (n=726), the J-PVAD risk score showed good discrimination ability (AUC 0.77 [95%CI 0.74–0.81]) and calibration (Figure B).

Conclusions:
The J-PVAD risk score can be calculated using variables easily obtained in routine clinical practice. It helps the accurate stratification of the risk for mortality and facilitates clinical decision-making.
Abstract 4141048: Inflammatory biomarkers predict long-term all-cause mortality in males but not in females.
Authors: Nilsen Dennis , Aarsetoey Reidun , Poenitz Volker , Ueland Thor , Michelsen Annika , Aukrust Pal , Brugger-Andersen Trygve , Staines Harry , Grundt Heidi
Published: November 2024

Background:
α1-antichymotrypsin (SERPINA3), high sensitivity C-reactive proten (hsCRP) and Pentraxin 3 (PTX3) are acute phase proteins triggered by inflammation. Hepatocytes are a primary source of SERPINA3 and CRP, while PTX3 is produced by a variety of tissues including endothelial cells. These inflammatory markers are upregulated after an acute myocardial infarction (AMI). Comparisons of their long-term prognostic value in acute coronary syndrome (ACS) patients by gender are scarce. We aimed to assess their long-term prognostic utility in females and males, respectively, hospitalized for chest pain of suspected coronary origin.

Methods:
A total of 871 consecutive patients (39.0% females) with a median age of 72.6 years (females 77.3, males 69.1) were admitted in the study. Of these, 386 were diagnosed with an acute MI based on Troponin-T (TnT) levels >50 ng/L. Stepwise Cox regression models, applying normalized continuous log
e
/SD values, were fitted for the biomarkers with total mortality within 7 years as the dependent variable.

Results:
At 7-year follow-up, 332 patients had died; 44.1 % females vs. 34.1 % males (χ
2
(1) = 9.368; p = 0.0022). Blood samples were available for analysis of SERPINA3, hsCRT and PTX3 in 847, 868 and 795 patients, respectively. There was no significant differences between the means of the sexes for SERPINA3 (p = 0.20), hsCRT (p = 0.84) and PTX3 (p = 0.068), respectively.

None of the biomarkers predicted long-term outcome in females after multivariable adjustment (p=0.92, p=0.40 and p=0.57, respectively), but were good predictors in males [SERPINA3: HR 1.34 (95%CI 1.16-1.56), p=0.00001. hsCRP: HR 1.19 (95%CI 1.02-1.38), p=0.027. PTX3: HR 1.22 (95%CI 1.04-1.44), p=0.018]. Furthermore, the p-values for interaction would suggest a gender difference in the prognostic weighting, favoring SERPINA3 (p=0.015) and to a lesser degree hsCRP (p=0.074) and PTX3 (p=0.14).

Conclusion:
SERPINA3, hsCRT and PTX3 are good predictors of long-term all-cause mortality in males admitted with chest pain of suspected coronary origin, but were not shown to predict outcome among females of that population. The prognostic utility of the studied inflammatory biomarkers may essentially be related to males.
Abstract 4141054: Management of Severe Non-Rheumatic Mitral Stenosis in Pregnancy
Authors: Caplan Alex , Nelson Favour , henry Lucie , Lesser Henry , Carry Brendan
Published: November 2024

Introduction:
Physiologic changes in pregnancy can accentuate valvular pathologies. The modified WHO pregnancy risk classification categorizes severe mitral stenosis (MS) as mWHO Risk Class IV in which pregnancy is contraindicated. Literature on the management of MS in pregnancy is limited to rheumatic heart disease. Those that are non-rheumatic in nature are therefore difficult to characterize. To better understand these differences in management, we present a case of MS from pannus-overgrowth 10 years after bioprosthetic valve placement.

Our Case:
A 29-year-old primigravid female, with a history of traumatic rupture of the posterior papillary muscle managed by a 25mm Carpentier-Edwards bioprosthetic mitral valve was seen at 13-weeks. A multidisciplinary (MDC) meeting was held with maternal-fetal medicine (MFM) and cardiothoracic surgery. A TEE confirmed severe MS [MVA 1.3cm
2
, mean gradient 19.5 mmHg, and peak velocity of 2.6 m/s] as the result of pannus-overgrowth limiting mobility in 1/3 leaflets. She was not a candidate for balloon valvuloplasty given her bioprosthetic valve, or valve replacement due to the risks cardiopulmonary bypass. She opted to continue pregnancy with medical management. As expected, in the mid-second trimester blood pressure reached its nadir, and her heart rate increased; therefore, metoprolol was started. Exposure to β-blockers is associated with fetal growth restriction (FGR) and the MFM team performed serial growth ultrasounds for close monitoring. At 28-weeks, she developed dyspnea, and the β-blocker dose was titrated. At 32-weeks these symptoms worsened, and furosemide was started. She experienced palpitations, but remote cardiac monitoring was reassuring. The pregnancy was complicated by non-severe FGR and so the MDC decided to pursue a medically indicated planned vaginal delivery in the intensive care unit (ICU) at 35-weeks. Delivery was accomplished via assisted second stage of labor to avoid maternal Valsalva. The postpartum course was uncomplicated. As she desired future childbearing, she underwent successful mechanical valve replacement after 3-months.

Discussion:
For pregnant patients with MS, heart rate and volume optimization are of critical importance. β-blockers and diuretics are safe and effective in pregnancy and providers should initiate these therapies as needed. We highlight the importance of an MDC approach in patients with MS and confirm that pregnancy and vaginal delivery can be safe.
Abstract 4141066: Multimodal Data-Based Longitudinal Prognostic Model for Predicting Atrial Fibrillation Recurrence after Catheter Ablation in Patients with Patent Foramen Ovale and Paroxysmal Atrial Fibrillation
Authors: Duan Shoupeng , Wang Daijiao
Published: November 2024

Background:
Clinical studies on atrial fibrillation (AF) recurrence after catheter ablation in patients diagnosed with patent foramen ovale (PFO) and paroxysmal AF (PAF) are scarce. Here, we aimed to develop a nomogram model utilizing multimodal data for the risk stratification of AF recurrence following catheter ablation in individuals diagnosed with PFO and new-onset PAF.

Methods:
Patients with PFO and PAF who underwent catheter ablation at our hospital from January 2018 to June 2020 were consecutively enrolled. The identification of potential risk factors was conducted using the regression method known as least absolute shrinkage and selection operator. Subsequently, multivariate COX regression analysis was conducted to determine the independent risk factors, after which a nomogram scoring system was developed. The nomogram's performance was assessed via various statistical measures, including receiver operating characteristic curve analysis, calibration curve, and decision curve analysis (DCA).

Results:
The dataset was partitioned into the development cohort (n=102) and the validation cohort (n=43) using a 7:3 ratio. The constructed nomogram included four clinical variables: age, diabetes mellitus, lipoprotein (a), and right ventricular diameter. The area under the curve values of the development and validation cohorts at 1, 2, and 3 years post-catheter ablation were 0.911, 0.812, and 0.786 and 0.842, 0.761, and 0.785, respectively. Additionally, the nomogram demonstrated a significant correlation between the predicted and actual outcomes in the development and validation cohorts, indicating its excellent calibration. Lastly, the DCA findings suggested that the model had notable clinical applicability in predicting the likelihood of AF recurrence within 1, 2, and 3 years after catheter ablation.

Conclusion:
The incorporation of multimodal data in a nomogram visualization tool facilitates the concise representation of multimodal data, thereby enhancing the comprehension of the clinical status of patients with PFO and PAF following catheter ablation and providing accurate risk stratification at 1, 2, and 3 years post-treatment.

Trial registration:
This trial was registered in the Chinese Clinical Trial Registry

(ChiCTR2300072320).
Abstract 4141078: Hearing the Voices of Families: Barriers and Facilitators of Pediatric Cardiac Ambulatory Care During the COVID-19 Pandemic
Authors: Wenren Larissa , Perez Maria , Fried Kira , Noymer Rebecca , Engstrand Shannon , Folks Tiffany , Jenkins Kathy , de Ferranti Sarah , Saleeb Susan , Connor Jean
Published: November 2024

Background:
Social determinants of health (SDOH)
,
exacerbated by the COVID-19 pandemic, impact access to medical care.

Research Question:
Through descriptive qualitative inquiry, we explored barriers and facilitators to pediatric cardiology ambulatory care for patients with complex congenital heart disease (CCHD) during COVID-19.

Methods:
English- and Spanish-speaking caregivers of children with CCHD who missed at least one clinic visit during the first year of COVID-19 were recruited, with purposeful sampling of Black and Hispanic patients. Semi-structured interviews inquired about the impact of the pandemic, experience with telehealth and communication with providers, effects of SDOH, and perceived impact of their race/ethnicity on care. Content analysis summarized information and identified themes.

Results:
Interviews (19) were conducted: 14 in English (6 Black, 2 Hispanic, 2 White, 3 mixed race, 1 American Indian), and 5 in Spanish (5 Hispanic). Overarching themes were: Barriers to Care, Facilitators of Returning/Staying in Care, Impact of Diagnosis, and Recommendations for Improvement (Image 1). Despite challenges with finances and transportation, as well as concern for infection risk, the majority of caregivers preferred in-person care over telehealth due to physical exam, diagnostic testing, and interpersonal connection with providers. SDOH challenges including housing, transportation, and employment contributed to missing care. For some families, social vulnerability was exacerbated by their child’s CCHD diagnosis and then again by COVID-19. Universally, caregivers felt their child’s race/ethnicity did not affect the care they received. Spanish-speaking caregivers expressed their primary language as a barrier to care and their desire for more thorough explanations and teach-back from the medical team.

Conclusion:
While SDOH can hinder access to ambulatory cardiac care, trusting relationships with care teams facilitated engagement. Social vulnerability contributed to dynamic situations for families, especially during COVID-19, highlighting the need for routine SDOH assessment and support. English- and Spanish-speaking caregivers echoed the same challenges. Race/ethnicity was not felt to impact care received.
Abstract 4141107: Genome-wide association study of aortic stiffness derived from deep learning in CMR images of 45,789 individuals identifies loci linked with cell-matrix structure
Authors: Paliwal Nikhil , Henry Albert , Finan Chris , Davies Rhodri , Hughes Alun , Williams Bryan , Malarstig Anders , Lumbers Tom , Hingorani Aaron
Published: November 2024

Background:
Aortic stiffness is associated with increased risk of cardiovascular events. Deep learning on large cardiac magnetic resonance (CMR) imaging samples has enabled detailed characterization of cardiac shape and function for use in genome-wide association studies (GWAS), leading to improved understanding of genetic aetiology of cardiovascular diseases (CVDs).

Aim:
We present a novel CMR-based pressure-independent measure of aortic stiffness, identify genetic factors and biological determinants using GWAS analysis of CMR imaging data from the UK Biobank.

Methods:
A pre-trained neural network was used to segment CMR images of participants in the UK Biobank to quantify ascending aorta diameter, which together with contemporaneous systolic and diastolic blood pressure measurements were used to calculate a pressure-independent measure of aortic stiffness (

β
0

). The measurement assumes an exponential relationship between pressure and aortic diameter. We performed a GWAS on

β
0

in 45,789 participants of European ancestry, excluding individuals with a prior history of CVDs. We performed stepwise conditional joint analysis to identify conditionally independent lead variants, and then defined a locus based on a 500kb flanking region centered on the variant. For each locus, we evaluated and combined scores from four complimentary approaches: variant-to-gene, polygenic priority score, gene-based association test and nearest gene. Candidate gene with the highest aggregate score was identified as the putative effector gene. We performed a pathway enrichment analysis for putative effector gene to identify potential biological pathways involving

β
0

.

Results:
We identified 17 independent lead variants from the GWAS (Figure A). We were able to identify putative effector genes at 16 of 17 genomic loci (Figure B, one locus was not resolved). Among the putative effectors were
ELN
and
LTBP4,
genes implicated in elastin fiber formation pathway (p=1.9E-2);
ELN, HAS2
and
LTBP4
associated with extracellular matrix assembly pathway (p=7.5E-3), and
ULK4, ARHGAP24, ELN, HAS2, SVIL, ARHGAP22, CDH13, SMG6
, and
LTBP4
linked to regulation of cellular component organization (p=2.6E-2).

Conclusion:
A GWAS of CMR-derived aortic stiffness identified 17 independent loci, suggesting its links with genetic influences on extracellular matrix and cellular component organization. These findings provide insights into the determinants of aortic stiffness that may inform future mechanistic studies.
Abstract 4141113: Sex, Race and Age Group Disparities in Pericardial Diseases Related Mortality Rates; Data from CDC Wonder 1999-2022
Authors: Abdul Rehman Khawaja , Sohail Rohab , Niazi Muhammad Ahsen , Mumtaz Ramsha , Arshad Faraz , Javeid Javeria , Godil Ansab , Sani Salman , Aftab Sameen , Akram Bisma , Zafar Sabin , Zaman Maham , Muhammad Zarlish Qazi
Published: November 2024

Background:
Pericardial Diseases (PD) have become a significant cause of morbidity and mortality over the last two decades. They contribute secondarily to deaths associated with other primary illnesses and can present clinically as pericarditis, pericardial effusion, and hemopericardium. Despite treatment advances, U.S. mortality trends for PD are unexplored.

Aim:
This study aims to assess the trends in PD-related deaths in the United States from 1999 to 2022.

Methods:
PD-related deaths in adults aged 25 years and above were identified through CDC WONDER database from 1999 to 2022 from multiple causes of death. Crude mortality rates and age-adjusted mortality rates (AAMR) per 100,000 population were determined. Joinpoint regression was used to examine changes in trends and annual percentage change (APC) overall, and then stratified by sex, ethnicity, and age groups.

Results:
A total of 105,536 deaths occurred from PD between 1999 to 2022. Overall, AAMR related to PD decreased from 1999 (2.4) to 2012 (1.7) (APC -2.73 [95% CI, -3.09 to -2.36]), then gradually increased until 2019 (2.0) (APC 2.92 [95% CI, 1.57 to 4.29]), followed by a sharp increase until 2022 (APC 7.65 [95% CI, 4.42 to 10.99]). After an initial decline, APC in AAMR increased in women (4.36) starting in 2012, while in men, it decreased significantly until 2011 (-2.26), followed by a slight increase until 2016 (1.05), and then a marked increase from 2016 to 2022 (4.19). After an initial decline, AAMR increased among non-Hispanic (NH) Blacks (APC 5.42) and NH Whites (APC 4.95) starting in 2014, among Hispanics (APC 4.10) from 2012 to 2022, and among NH Asian or Pacific Islanders (APC 2.4) from 2007 to 2022. Mortality rates have been steadily increasing across all age groups over the last decade, with the highest increase seen recently in the 85+ age group (2017-2022 APC 9.09 [95% CI, 6.50 to 11.76]).

Conclusion:
PD-related mortality has increased over the last decade. Mortality among males, NH Blacks, and the 85+ age group has been growing at a faster rate than any of the other groups. These results highlight the need for further investigation into the factors contributing to the observed disparities and trends in PD mortality rates.
Abstract 4141118: Identifying PDK4 as A Metabolic Regulator in Pulmonary Arterial Hypertension: Insights from Bulk, Single-cell Transcriptomics Analysis and Clinical Validation
Authors: Yang Lingzhi , Huang Wei
Published: November 2024

Objective:
Pulmonary Arterial Hypertension (PAH) is a fatal disease with high mortality rates and late diagnosis, currently lacking complete cure. Metabolic abnormalities play a crucial role in the pathophysiological process of pulmonary vascular remodeling. This study aimed to identify metabolic-related genes that may play important roles in PAH and analyze their expression and function and the clinical significance.

Methods:
Transcriptomic data were retrieved from the GEO database, including tissue transcriptome data (GSE113439, GSE53408, GSE198618) and single-cell transcriptome data (GSE210248, GSE203274); "limma" and "DEseq2" packages were used to identify differentially expressed genes (DEGs); By WGCNA and Boruta algorithm, we identified feature genes related to PAH; Transcription factor network analysis was analyzed using the "RTN" package; Single-cell and single-nucleus transcriptome data were analyzed using the Seurat pipeline; Concentration of key genes’ protein level in PAH were evaluated using ELISA.

Results:
The study found increased glycolysis, disrupted carnitine shuttle pathway, enhanced fatty acid degradation, decreased oxidative phosphorylation, and augmented polyamine synthesis in PAH. PIGN, SLC25A24, RPL5, PIK3CA, PIK3CB, DNM1L, SETD2, TPH1, ITPR2, PRKAA1, PTPN11, and PDK4 were identified as metabolic-related genes associated with PAH. PDK4 was significantly increased in pulmonary artery endothelial cells (PAECs) and right ventricular tissues of decompensated right heart failure, mainly expressed in cardiomyocytes. PDK4 was significantly elevated in the PAH group (control group: 4.15 ± 0.53 ng/ml; idiopathic pulmonary arterial hypertension group: 5.28 ± 0.77 ng/ml, p-value <0.001), and showed linear correlations with mean pulmonary artery pressure (r=0.51, p=0.00033) and pulmonary vascular resistance (r=0.44, p=0.0019).

Conclusion:
This study provides important insights into the role of metabolic reprogramming and mitochondrial dysfunction in the pathogenesis of PAH, identifies 12 potential pathogenic regulatory factors related to metabolism, and suggests that PDK4 is strongly correlated with hemodynamic parameters of the disease, potentially participating in PAH and cardiac remodeling under right heart overload.