bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13147: The Internally Translated Isoform of Connexin 43, GJA1-20k Rescues Cx43 Trafficking and Reduces Arrhythmias in the DSG2 Mutant Model of Arrhythmogenic Cardiomyopathy
Authors: Palatinus Joseph A , Valdez Steven , Whisenant Claire , Kleber Andre G , Saffitz Jeffrey E , Shaw Robin M
Published: April 2024

Introduction:
Arrhythmogenic cardiomyopathy (ACM) is an inherited condition caused by mutations of junctional proteins resulting in heart rhythm abnormalities, heart failure and sudden cardiac death. ACM subjects exhibit a loss of normal trafficking of the gap junction protein Connexin 43 (Cx43) to the intercalated disk. Our group has previously demonstrated that the Cx43 gene, GJA1, undergoes internal translation to form multiple truncations of the full-length protein. The 20 kilodalton isoform, (GJA1-20k) is required for trafficking of Cx43 gap junction channels, and exogenous expression of GJA1-20k increases trafficking of full length Cx43 to the membranes and the intercalated disk. Here, we hypothesize that GJA1-20K will reduce dysrhythmias by improving trafficking of Cx43 to the intercalated disc in a mouse model of ACM.

Methods:
Desmoglein 2 (DSG2) homozygous knock-out mice, producing a typical ACM phenotype, were injected with a viral vector containing either GJA1-20K-GFP or GFP alone at four weeks of age along with wild-type littermate controls. Echocardiography was performed every four weeks and Telemetry was recorded at ~18-19 weeks of age to record cardiac electrical activity over a continuous 12 hour period. At 20 weeks, the mice were sacrificed, and hearts were harvested for further analysis.

Results:
Compared to WT littermates DSG2-KO mice that received a GFP viral vector demonstrated over a 100 fold increase in mean number of PVCs observed over a 12 hour period (2 vs 371 respectively p=0.0005). Mice that received the GJA1-20k viral vector in contrast demonstrated significantly fewer PVCs than their GFP treated littermates 43 vs 371. (analysis of variance of Log(#PVC) p =0.015 N = 6-7 mice/group). Quantitative immunofluorescence analysis of hearts confirmed an increase in Cx43 localization at the intercalated disk (as measured as a percent of N-Cadherin-Cx43 colabeling) in mice treated with GJA1-20k relative to GFP (25% vs 6% respectively N= 7 images/mouse and 3 mice/ group) t-test p=0.0009).

Conclusions:
Our data indicate that GJA1-20K significantly reduces the number of PVCs and recovers Cx43 trafficking to the intercalated disk in a mouse model of ACM. Our results point to a therapeutic option for the treatment of ACM related arrhythmias.
Abstract 13196: Highly Active Antiretroviral Therapy-related Complications And Associated Genetic Susceptibility Variants In Hiv-infected Patients With Pre-existing Heart Failure: A 7-year Prospective Cohort Study
Authors: Ma Kevin Sheng-Kai
Published: April 2024

Introduction:
HAART-associated metabolic syndromes have been reported, without such risk and genetic markers in patients with pre-existing heart failure (HF) being addressed.

Hypothesis:
We hypothesize that compared with HIV-infected patients without HF undergoing HAART, patients with pre-existing HF are at higher risk of long-term HAART-related metabolic complications, which is associated with genetic variants.

Methods:
In this prospective cohort study 172 HIV-infected patients were recruited and followed-up since 2013. Demographic and medical records such as weight, BMI, drug use, lab data of blood and urine, HAART regimens, Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) CVD risk scores, were recorded. Multivariate regression model was used to derive risk of adverse outcomes following HAART in HF patients, compared to matched-patients without HF. GWAS was conducted in HF patients to investigate genetic variants associated with adverse events susceptibility.

Results:
After matching on baseline, HAART was effective for both patients with or without HF, at a similar viral load (r=0.001, P=0.69) and CD4 count (r=-0.06, P=0.48). D:A:D (R) (r=0.002, P=0.97) and D:A:D (F) (r=0.04, P=0.62) CVD risk scores were comparable in patients with and without HF. Patients with HF presented with higher risks of subsequent T2DM (r = 0.24, P=0.01) and increased total cholesterol (r=0.23, P=0.006), LDL (r=0.18, P=0.04), and uric acid (r=0.35, P=0.004), compared to those without HF. Four independent SNPs in ABCG2 (rs717620), PNPLA3 (rs738409), CYP2A6 (rs28399433), and CYP2B6 (rs2279345) reached genome-wide significance for their associations with HAART-related complications in patients with HF, including ABCG2 for subsequent advanced stages CKD (eGFR < 30), PNPLA3 for increased HDL levels, CYP2A6 for increased BUN levels, and CYP2B6 for hematuria.

Conclusions:
HAART was equally effective for HIV management in HF patients, and did not result in more subsequent cardiotoxicities, compared with those without HF; however, increased risk of T2DM, and increased levels of CHO, LDL, and uric acid during follow-ups, were observed. Genetic susceptibility variants associated with HAART-related complications in HF patients were demonstrated.
Abstract 13662: Superior Vena Cava Blood Up-Regulates RNA Expression of Vascular Remodeling Pathways in Lung Endothelial Cells
Authors: Spearman Andrew D , Gudausky Todd M , Foerster Susan R , Konduri Girija G , Ramchandran Ramani
Published: April 2024

Introduction:
Pulmonary arteriovenous malformations (PAVMs) are common sequelae of single ventricle congenital heart disease (CHD), yet their pathogenesis are poorly understood. Clinical observations indicate that superior vena cava (SVC) blood induces PAVMs, whereas hepatic vein (HV) blood prevents and resolves PAVMs. Using paired SVC and HV blood samples from children with single ventricle CHD, we previously identified multiple protein differences between HV and SVC serum. To determine whether HV and SVC serum differentially impact gene expression in lung endothelial cells, we compared mRNA levels after incubation with HV and SVC serum.

Hypothesis:
We hypothesize that HV serum induces gene expression associated with endothelial quiescence, whereas SVC serum promotes genes expression associated with vascular remodeling.

Methods:
HV and SVC blood were collected in the cardiac catheterization lab from children with single ventricle CHD and Glenn circulation. HV and SVC serum (10% concentration) were incubated with human pulmonary microvascular endothelial cells (PromoCell) for 48 hours. After RNA isolation and reverse transcription, mRNA levels of 84 target genes were quantified using Qiagen RT
2
Profiler Angiogenesis Array (PAHS-024Z). Statistically significant differences in expression were identified with absolute fold difference >1.2 and p < 0.05.

Results:
Samples from 8 patients (63% male, median age 40 months [25.75, 45.25]) were included. Fifteen genes were differentially expressed, including 2 over-expressed with HV treatment (ANGPTL4 [+1.78 fold] and FGF1 [+1.46]) and 13 over-expressed with SVC treatment. Multiple processes were up-regulated in the SVC cohort: VEGF signaling (VEGFR2 [-1.21 fold], NRP1 [-1.42], VEGFR1 [-1.49]), EC adhesion/migration (ITGB3 [-1.40], EFNA1 [-1.40], EFNB2 [-1.39]), angiopoietin-TIE signaling (TIE2 [-1.31]), pericyte signaling (PDGF-A [-1.50], monocyte recruitment (CCL2 [-2.09]), and matrix remodeling (MMP2 [-1.65], FN1 [-1.33]).

Conclusions:
SVC serum up-regulates multiple vascular remodeling pathways in lung microvascular endothelial cells, potentially representing a pathologically activated endothelial phenotype. In contrast, HV serum promotes endothelial quiescence.
Abstract 13668: Out-of-Pocket Health Spending and Subjective Financial Hardship in Atherosclerotic Cardiovascular Disease and Heart Failure in the United States
Authors: Wang Stephen Y , Valero Elizondo Javier , Nasir Khurram , Khera Rohan
Published: April 2024

Introduction:
Financial burden from healthcare expenses in families with members with CVD like ASCVD and HF have focused on studying either the costs incurred by patients or their subjective challenges with paying medical bills. We evaluated the full extent of financial toxicity of healthcare on patients with CVD, which has implications for cost-based quality measures and designing interventions.

Methods:
All families with ≥1 member with ASCVD or HF in the Medical Expenditure Panel Survey (MEPS), 2014-18, were included. Objective financial hardship (OFH) was defined as annual out-of-pocket medical expenses exceeding 20% of annual income. Expenses included care costs and insurance premiums. Subjective financial hardship (SFH) was defined as self-reported problems with paying medical bills, medical bills being paid over time or inability to pay medical bills.

Results:
There were 10,390 families in MEPS with ≥1 member with ASCVD, representing 21 million families nationally, and 783 families in MEPS with ≥1 HF member, representing 1.7 million families nationally. Among families with ASCVD, 12.4% (95% CI 11.5% - 13.3%) experienced OFH, and 26.6% (25.4% - 27.7%) reported SFH. Collectively, 35% (33% - 36%) experienced either OFH or SFH, but only 4.4% (3.9% - 4.8%) experienced both (Fig A). Similarly, in HF, 43% families experienced at least one form of financial burden, but fewer experiencing OFB rather than SFB burden (14.1% vs 35.5%), and only 6.1% (95% CI 3.9% - 8.4%) experienced both. There patterns were consistent across key subgroups, but younger age and high income were associated with discordant OFH and SFH (Fig B).

Conclusions:
In 2014-18, nearly 50% of families with ASCVD or HF experienced financial hardship from medical expenses, but a focus on objective or subjective measures alone would have captured only half the burden. Measurements of financial toxicity and a study of mechanisms would need to assess factors underlying both objective and subjective measures.
Abstract 13701: Short Term Outcomes of Takotsubo Cardiomyopathy in Patients With Right Ventricular Dysfunction in the US Veteran Affairs Healthcare System
Authors: Alqam Bilal , Habash Fuad , Gheith Zaid , VALLURUPALLI SRIKANTH , Maskoun Waddah
Published: April 2024

Introduction:
Takotsubo cardiomyopathy is characterized by significant transient left ventricular dysfunction that is not due to obstructive coronary artery disease, but concurrent right ventricular (RV) dysfunction has been described previously. The aim of our study was to investigate the rates and outcomes of patients diagnosed with Takotsubo cardiomyopathy with RV dysfunction in the Veteran Affairs (VA) system.

Methods:
We performed a retrospective study using chart review for patients diagnosed with Takotsubo cardiomyopathy between 2005 and 2018 in the VA national database. We included patients who met the Mayo Clinic diagnostic criteria for Takotsubo cardiomyopathy. We collected data for demographics, clinical course, and outcomes.

Results:
276 patients (70% males) were included. Median age was 64 years, 18.5% were known to have coronary artery disease, 34.8% had Diabetes and 58.1% had hypertension. 96.3% of patients had apical variant of Takotsubo cardiomyopathy. Biventricular dysfunction was identified in 14.1% of patients; of those 71.8% were identified as new RV dysfunction in which 92.3% were apical. There was no significant difference in the in-hospital mortality rates between patients with new biventricular dysfunction compared to patients with normal RV function or old RV dysfunction (10.7% vs 8.1%, p = 0.63). There was also no significant difference in 30-day mortality rates between patients with new biventricular dysfunction compared to patients with normal RV function or old RV dysfunction (4.2% vs 1.8%, p = 0.45). Similar findings were observed when patients with previous RV dysfunction were excluded. On follow up echocardiogram 96.3% of patients who survived had full recovery of their RV function.

Conclusions:
In patients diagnosed with Takotsubo cardiomyopathy with new RV dysfunction, there was no significant difference in mortality rates in the hospital or at 30-day follow up.
Abstract 13703: Outpatient Cardiac Rehabilitation Reduces Heart Failure Re-Hospitalization in Patient With Heart Failure With Reduced Ejection Fraction When Compared to Patients With Heart Failure With Preserved Ejection Fraction
Authors: EMMANUEL KELECHI , Lawal Halimat , Valenzuela Guillermo , Wert Yijin
Published: April 2024

Introduction:
Cardiac rehabilitation has been increasingly recognized as an integral part in the management of patients with congestive heart failure. It has been shown to improve the quality of life in this patient population. However, It is unknown how much cardiac rehabilitation reduces heart failure hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF).

Hypothesis:
We hypothesize that outpatient cardiac rehabilitation is associated with reduced re-hospitalization for heart failure symptoms in patients with heart failure with HFrEF when compared with patients with HFpEF.

Methods:
We retrospectively analyzed data from 128 heart failure patients enrolled in an outpatient cardiac rehabilitation center from January 2015 to December 2020. The number of heart failure re-hospitalizations was measured in each of these patients. A Student t-test was used to analyze the difference between the two groups, while fisher’s test or chi square was used to analyze categorical variables.

Results:
Among the 128 patients enrolled in the outpatient cardiac rehabilitation center, age 68.1+-14 years, 63 (57.1%) were males. There were 70 patients (54.6%) in the HFrEF group and 58 (55.28%) in the HFpEF group. Hospitalization for acute exacerbation of heart failure symptoms was lower in the patients with HFrEF when compared with patients with HFpEF (41.3% vs 70.69% p value <0.0009).

Conclusion:
Outpatient cardiac rehabilitation program is associated with reduced hospitalization for heart failure symptoms in patients with HFrEF when compared to patients with HFpEF.
Abstract 13731: Randomized Trial of CMR Guidance for Cardiac Resynchronization Therapy: Findings in Nonischemic Cardiomyopathy From an Interim Analysis
Authors: Bilchick Kenneth C , Gao Xu , Abdi Mohamad , Oomen Pim , Bivona Derek , Tallavajhala Srikar , Mazimba Sula , Mason Pamela K , Malhotra Rohit , Kramer Christopher M , Epstein Frederick
Published: April 2024

Introduction:
Cardiac resynchronization therapy (CRT) response rates in unselected cohorts are suboptimal. Cardiac magnetic resonance (CMR) provides high-quality imaging of strain and scar, and post-CRT CMR offers reliable assessment of left ventricular (LV) reverse remodeling.

Hypothesis:
Cardiac magnetic resonance (CMR) guidance for CRT will increase CRT response rates, particularly in nonischemic cardiomyopathy (NICM).

Methods:
Patients were randomized 1:1 to standard CRT or CMR guidance for CRT using circumferential strain from Displacement Encoding with Stimulated Echoes (DENSE) and scar (late gadolinium enhancement [LGE]) by CMR. The primary endpoint is the percent change in LV end-systolic volume (LVESV) calculated from CMRs before CRT and 6 months after CRT. A pre-specified interim analysis by cardiomyopathy type was performed after completion of enrollment of 45 of the projected 90 patients needed for adequate power.

Results:
Of 45 patients enrolled (age 65.9 +/- 10.3 years, 29% female), two patients did not undergo a CRT procedure, and the LV lead could not be placed in one patient. Of the remaining 42 patients, 26/42 had NICM and 21/42 were randomized to CMR guidance. In a linear regression model for the primary endpoint adjusted for baseline QRS duration (p=0.04) and cardiomyopathy type (p=0.01), a favorable trend for the intervention on response was noted (p=0.06). Box plots demonstrate a significant difference in the primary endpoint among NICM patients (p=0.03) and a favorable trend for QRS shortening (0.07) in NICM patients (Figure). In all patients (including ICM patients), the overall p-value for the intervention relative to the primary endpoint was 0.08.

Conclusion:
An interim analysis in CRT patients with NICM demonstrated a favorable effect of CMR guidance on LV reverse remodeling after CRT, as assessed with post-CRT CMRs. Enrollment is continuing to evaluate the effect of the intervention on the entire cohort and other endpoints.
Abstract 13739: Emergency Medical Services Calls During COVID-19: Bottleneck Explained
Authors: Al Amiry Alaa , Maguire Brian
Published: April 2024

Background:
During COVID-19 peak in 2020, EMS calls have surged unprecedently internationally, causing global disruption in EMS dispatch centers’ services and significant delays in emergency response worldwide. This negatively impacted the chain of survival for cardiac and stroke, and other emergencies. No studies yet have been done to examine this phenomenon globally.

Objectives:
This paper examines the interrelated effects of the unprecedented global increase of EMS calls, the effect of the COVID-19 crisis on responding to non-COVID-19 emergencies; mainly cardiac and stroke emergencies- among others, and the concurrent effects of having overwhelmed dispatch centers. We examined the bottleneck phenomenon that resulted in the disruption of EMS calls in different countries, and found three main factors: 1.EMS-related factors 2.Social-related factors 3.Patient-related factors. For better understanding, we also explained each factor based on the available literature.
Eligibility Criteria
: We examined the numbers of EMS calls internationally between March and June 2020, derived from published literature and news media. Only articles in English were selected, with certain keywords related to EMS calls, ambulance delay, stroke and cardiac arrest.

Results:
After applying the selection criteria, a total of 29 citations were chosen, and a pattern of knowledge resulted in the emergence of five themes: •EMS calls during COVID-19 •Reduced EMS operator response time •Ambulance response delays •Collateral mortality and morbidity among non-COVID-19 cases

•Total ambulance call time

Conclusion:
Over the course of COVID-19 progress, there was a global phenomenon of exponential increases in EMS calls, which is expected to impose a great pressure on EMS dispatch centers. Several factors contributing to the bottleneck of EMS calls are identified and explained. By understanding these factors and their collateral impact on EMS calls, we can implement better crises and disaster response plans. This is an informative paper to EMS decision makers worldwide.

Key words:
EMS calls, COVID-19, Ambulance response time, Pandemic response, EMS access, Ambulance delay
Abstract 13748: Feasibility Of Quantitation Coronary And Aortic Valve Calcification In Virtual Non-contrast Images From Dual-energy Delayed Ct Scans In Patients With Severe Aortic Stenosis
Authors: Han Donghee , Tamarappoo Balaji , Kwan Alan C , Makkar Raj , Dey Damini , Friedman John , Berman Daniel S
Published: April 2024

Introduction:
Increased extracellular volume (ECV), is a prognostically important marker of myocardial fibrosis in patients with severe aortic stenosis (AS). ECV can be assessed during transcatheter aortic valve replacement planning CT (TAVR CT) scan by adding a dual-energy CT (DECT) delayed image. TAVR CT scans routinely include a traditional non-contrast scan (TNC) for coronary artery calcium (CAC) and aortic valve calcium (AVC) scoring. Virtual non-contrast (VNC) images, derived from the DECT could replace TNC for CAC and AVC scoring, and reducing radiation and scan time. We examined the adaptability of VNC as a substitute for TNC by comparing CAC and AVC scoring based on VNC from delayed DECT scans compared to TNC in severe AS patients.

Methods:
We enrolled 27 severe AS patients who underwent TNC CAC scan and delayed DECT scan as part of TAVR CT using a dual-source scanner (Somatom Flash, Siemens). VNC was reconstructed with postprocessing software (Syngo Dual Energy, Siemens). CAC was categorized as 0, 1-99, 100-399, 400-999 and ≥1,000. Severe AVC was defined as >2,200 for men and >1,200 for women.

Results:
Both CAC and AVC scores in VNC demonstrated excellent correlation with TNC (r=0.975 and 0.982). The CAC score was significantly lower in VNC compare to TNC (745.2 ± 923.6 vs. 1006.4 ± 1116.9, p<0.001). AVC score did not significantly differ between VNC and TNC (2000.8 ± 2791.6 vs. 1911.5 ± 2186.8, p=0.567). Three patients (3/27) were categorized to a CAC category one grade lower than TNC by VNC DECT (Figure). One patient with non-severe AVC by TNC was misclassified as having severe AVC by VNC (1/27) (Figure).

Conclusions:
VNC DECT underestimates CAC compared to TNC, but the differences in CAC score rarely resulted in categorical discordance in severe AS patients. VNC from DECT delayed scan for ECV assessment can assign patients to the correct cardiovascular risk categories based on CAC and performs adequately for clinically meaningful AVC scoring in severe AS patients.
Abstract 13754: Association of Cumulative Excess Adiposity With Heart Failure With Preserved and Reduced Ejection Fraction: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Wondmagegn Admasu Y , Echouffo Tcheugui Justin B , Zhang Sui , Sharma Kavita , Matsushita Kuni , Shah Amil M , Loehr Laura R , NAMBI VIJAY , Florido Roberta , Chang Patricia , Ballantyne Christie M , Coresh Josef , Ndumele Chiadi E
Published: April 2024

Background:
Prior studies suggest that obesity, measured at a single time point, has a stronger association with heart failure with preserved ejection fraction (HFpEF) than heart failure with reduced ejection fraction (HFrEF). Longstanding obesity is associated with both diastolic and systolic dysfunction, but there is scarce data on the association of cumulative adiposity with risks for HFpEF and HFrEF.

Hypothesis:
Higher cumulative adiposity is associated with increased risk for both HFpEF and HFrEF.

Methods:
We performed a prospective analysis of 8,895 individuals (mean age 63, 57% women, 19% Black adults) without HF or coronary heart disease (CHD) who attended ARIC Visit 4 (1996-99). We calculated cumulative excess body-mass index (BMI) years from age 25 to Visit 4 by centering the BMI variable at 25 kg/m2 at each of the first 4 ARIC visits and at age 25 (self-reported), and multiplying the average BMI by the number of years from age 25 to Visit 4. Cumulative excess BMI years were categorized into quartiles. The outcomes were cases of incident HFpEF (EF ≥50%) and HFrEF (EF <50%) during the period of HF adjudication in ARIC (1/1/2005-12/31/2019); we excluded those with HF prior to 2005. We used Cox models to calculate incidence rates and estimate hazard ratios (HRs) for the associations of cumulative excess BMI years with incident HFpEF and HFrEF, adjusting for covariates including incident CHD.

Results:
There were 554 HFpEF and 482 HFrEF events over 14 years of follow-up. Higher quartiles of cumulative excess BMI years were associated with greater incidence of HFpEF and HFrEF (Table). Compared to the lowest quartile, the highest quartile of cumulative excess BMI years was associated with greater risk for HFpEF (HR: 1.57, 95% CI 1.22-2.03) and HFrEF (1.50, 95% CI 1.13-1.99).

Conclusions:
Excess cumulative weight is associated with similarly increased risks of HFpEF and HFrEF, indicating the importance of obesity prevention for reducing the risks for different subtypes of HF.
Abstract 13785: Profile and Characteristics of Peripheral T Cell Receptor Repertoires in Patients With Rheumatic Heart Disease Through High-Throughput Sequencing
Authors: Zhang Lu , zeng kuan , Gao Minnan , Li Jianfen , Jiang Huiqi , Liu Congyong , Yang Yanqi
Published: April 2024

Introduction:
Valve damage in rheumatic heart disease (RHD) is caused by immune cross-reaction to A streptococci attacking heart valve tissue of the host in which T cell is thought to play a key role. However, the immunological mechanism of is still poorly understood. The aim of the present study is to assess T cell receptor (TCR) repertoires in patients with RHD in comparison with healthy individuals.

Hypothesis:
T cells play a key role in regulating cell mediated immune response associated with heart valve damage in RHD.

Methods:
In the study, 21 subjects were enrolled, including 11 patients with RHD matching the diagnostic criteria of 2020 ACC/AHA guideline who accepted valve surgery, and 10 healthy individuals. The patient group had an average age of 52.5 years and 36.4% male. The healthy group had an average age of 37.1 years and 50% male. The TCR repertoires in all subjects were assessed by using high-throughput sequencing. Bio-informatics analysis was performed.

Results:
The overall immune characteristics of the patients and healthy individuals are obviously different. The TCR repertoire in the patients with RHD presented a significantly lower diversity than that in the healthy (D50-p<0.05) which implied that number of frequently expressed clonotypes were fewer in the patient group than that in the healthy group. The average fraction of the top 200 TCRs sequences was 20.95±8.89% in the patients which was significantly greater than that of 17.59±4.93% in healthy individuals (p<0.05), suggesting the TCR distribution in the patient group was more concentrated than in the healthy group. Heterogeneity of TCR repertoire was more pronounced in the patient group comparing to those in the healthy group (p<0.01). Both clonotype feature and TRBV-J combination feature of TCRs profile in the patient group demonstrated significant specificity for RHD(AUC>0.84, p< 0.05 and AUC>0.93, p< 0.05).

Conclusions:
TCR repertoires in patients with RHD is different from that in healthy individuals. The characteristics of TCR repertoires in patients with RHD indicated specific T cell response in the development of the disease,which provided clues to searching for biomarkers for early diagnosis of RHD and early blocking.
Abstract 13790: Long-Term Mortality After Acute Myocardial Infarction According to Presence of Modifiable Risk Factors
Authors: Puymirat Etienne , El Kharchi Mohamed , Tea Victoria , Ferrieres Jean , Schiele Francois , Simon Tabassome , Danchin Nicolas
Published: April 2024

Introduction:
Acute myocardial infarction (AMI) in the absence of modifiable risk factors (MRF) might have a poorer outcome.

Methods:
we assessed long-term survival in the FAST-MI program (3 nationwide French prospective surveys carried out 5 years apart from 2005 to 2015, consecutively including STEMI and NSTEMI patients ≤48 hours from onset, over 1-month periods), according to presence/absence of MRF (current smoking, hypertension, diabetes, obesity or hypercholesterolemia/statin use).

Results:
Of 13,310 patients included, 9,599 had no history of CAD, of whom 1503 (15.6%) had no MRF; they were older (66 ± 13 vs 64 ± 14 years, P<0.001) with similar GRACE score (141 ± 33 vs 140 ± 36, P=0.54) and LVEF (52 ± 11 vs 53 ± 11, P=0.17), were more frequently men (74 vs 70%, P=0.001) and had more often STEMI (63 vs 58%, P<0.001). Use of coronary angiography and PCI did not differ, 1-vessel disease was more common in patients without MRF (58 vs 52%, P<0.001); at discharge, statin (90 vs 90.5%; moderate/high dose 69 vs 67%), dual antiplatelet (84 vs 85%) and beta-blocker (85 vs 84%) use did not differ, while fewer received ACEi or ARBs (72 vs 75%, P=0.03). At a mean follow-up of 54 months, survival was higher in patients without MRF (88 vs 84%, P<0.001); NSTEMI patients (89 vs 81%, P<0.001), STEMI patients (88 vs 86%, P=0.21) (Figure). After adjustment on baseline variables, absence of MRF was not associated with long-term mortality (HR 0.88, 95%CI 0.72-1.09); however, when also including early management, LVEF and CAD extent in the model, absence of MRF was associated with lower mortality (HR 0.76, 95%CI 0.62-0.92, P<0.001).

Conclusion:
the management of patients with AMI is very similar, whether they have MRF or not. Long-term survival does not differ among patients with or without MRF. After taking into account early management, however, presence of MRF is associated with worse outcome, suggesting that more intensive treatment might be needed when AMI occurs in patients with documented risk factors.
Abstract 13793: The Impact of Right Ventricular Trabeculation in Patients With Left Ventricular Noncompaction
Authors: Kiss Anna Reka , Gregor Zsofia , Popovics Adrian , Grebur Kinga , Liliana Szabo , Dohy Zsofia , Kovacs Attila , Lakatos Balint , Merkely Béla , Vágó Hajnalka , Szucs Andrea
Published: April 2024

Right ventricular (RV) involvement in left ventricular noncompaction (LVNC) remains unknown. We aimed to describe the RV volumetric, functional, and strain characteristics and clinical features of patients with LVNC and good LV ejection fraction (EF) using cardiac magnetic resonance, to identify differences between LVNC patients with (RV-HT) and without RV hypertrabeculation (RV-NT) and to describe the relationship between RV and LV trabeculation and RV volume and function. One hundred Caucasian patients with LVNC and good LV-EF and 100 age- and sex-matched healthy controls were included in this retrospective study. Patients were further divided into two subgroups by the amount of RV indexed trabecular mass (RV-TMi). We measured the LV and RV volumetric, functional and TMi values using threshold-based postprocessing software and the RV and LV strain values using feature tracking and collected the patients’ LVNC-related clinical features. Patients had higher RV volumes, lower RV-EF and worse RV strain values than controls. A total of 22% of patients had higher RV-TMi values than the previously described reference range; furthermore, RV-HT patients had higher RV and LV volumes, lower RV- and LV-EF and worse RV strain values than RV-NT patients. We identified a strong positive correlation between RV- and LV-TMi and between RV-TMi and RV volumes and a significant inverse relationship between both RV- and LV-TMi and RV function. The prevalence of LVNC-related clinical features was similar in the RV-HT and RV-NT groups. These results suggest that some LVNC patients might have RV noncompaction with subclinical RV dysfunction, raising further questions about its prognosis.
Abstract 13808: Impact of Complex Percutaneous Coronary Intervention Features Among Patients With or Without Chronic Kidney Disease
Authors: Nicolas Johny , Cao Davide , Zhang Zhongjie , Sartori Samantha , Pivato Carlo Andrea , Tavenier Annerieke , Beerkens Frans , Camaj Anton , Razuk Victor , Jones Davis , Chiarito Mauro , Baber Usman , Sweeny Joseph , Krishnan Prakash , Sharma Samin K , Kini Annapoorna , Dangas George , Mehran Roxana
Published: April 2024

Introduction:
Among patients undergoing percutaneous coronary intervention (PCI), those with chronic kidney disease (CKD) sustain poor clinical outcomes. However, there is a paucity of data on the impact of complex PCI (CPCI) on long-term prognosis, according to the presence of CKD.

Objective:
To determine the prognostic impact of complex procedural features in patients undergoing PCI with and without CKD.

Methods:
Patients undergoing PCI at a tertiary-care center between 2012 and 2019 were stratified according to the presence of CKD and procedural complexity. A CPCI was defined by the presence of ≥1 of the following: stent length >60 mm, ≥3 stents, ≥3 lesions, ≥3 target vessels, bifurcation with ≥2 stents, or chronic total occlusion. The primary outcome of interest was major adverse cardiac events (MACE), a composite of death, myocardial infarction (MI) and target vessel revascularization (TVR) at 1 year.

Results:
Out of 15,071 patients, our study population consisted of 4,537 (30.1%) with CKD of whom 1,151 (25.4%) underwent CPCI, while 2,983 (28.3%) patients without CKD underwent a CPCI. The prevalence of traditional risk factors was similar among patients within the same group (CKD and no-CKD), irrespective of PCI complexity. Nonetheless, patients undergoing CPCI had more extensive coronary artery disease (i.e., higher syntax score, severe calcification, and longer lesion length). CPCI was associated with a higher risk of MACE at 1 year in both groups, though a greater risk was observed in those without concomitant CKD, mainly driven by a higher risk of MI and TVR (Figure 1). However, the risk of all-cause death was significantly higher among CKD patients undergoing a CPCI, and there was no significant difference between those with and without CPCI in non-CKD group.

Conclusions:
CPCI is associated with an increase in the risk of 1-year MACE among patients with or without CKD. The larger increase in the risk of MACE is observed in those without CKD, than those with CKD.
Abstract 13906: Excess Epicardial Fat Volume is a Novel Risk Marker for Cardiovascular Disease Risk Assessment, Beyond Coronary Artery Calcium Score
Authors: El Shahawy Mahfouz , Schultz Katelyn , Mohan Sukanya , Sabatini Antonella , Palmer Genevieve
Published: April 2024

Introduction:
Excess epicardial fat volume (EFV) is reported to be associated with cardiovascular structural and functional abnormalities.

Hypothesis:
The purpose of this study is to assess whether excess EFV is associated with structural and functional changes, regardless of coronary artery calcium score (CACS).

Methods:
2,892 untreated and asymptomatic subjects were screened for cardiovascular risk using the Early Cardiovascular Health Risk Scoring System (ECVHRS). The ECVHRS consists of 10 tests; 7 of which are vascular, and 3 are cardiac. The vascular tests are as follows: large (C1) and small (C2) artery stiffness, blood pressure (BP) at rest and post-mild exercise protocol (PME), carotid intima-media thickness (CIMT), abdominal aorta ultrasound, retinal photography, and microalbuminuria. The mild exercise protocol involves a 3-minute walk on a treadmill at 7% elevation and a speed of 2.5 miles per hour. The BP was measured at rest and immediately after completion of the 3-minute walk. An abnormal rise in BP-PME is defined as a systolic BP rise of ≥ 30 mmHg, a systolic BP ≥ 170 mmHg, or a diastolic BP ≥ 90 mmHg. The 3 cardiac tests are as follows: pro-BNP, electrocardiogram (ECG), and left ventricle ultrasound (LVUS). The ECG and LVUS were individually interpreted for abnormalities. Out of these 2,892 subjects, 328 were evaluated for CACS and EFV using a cardiac CT scan.

Results:
As seen in the table below, the subjects in Group 1 (n=35), with an excess amount of epicardial fat (EFV ≥ 94 cm
3
) averaging 151.63 cm
3
, were associated with statistically significant structural and functional abnormalities, as compared with Group 2 (n=22), with a normal average EFV of 70.77 cm
3
.

Conclusions:
Based on our data, we posit that it is time to think beyond CACS as the mainstay determining factor for CVD risk. In our study population, EFV has a greater influence and correlation with cardiac structural and functional abnormalities. Time to focus on assessing EFV on cardiac CT scan.
Abstract 13917: A Harmonized Meta-Analysis of the Associations of Steps per Day With Incident Cardiovascular Disease
Authors: Paluch Amanda E , Bajpai Shivangi , Bassett David R , Chernofsky Ariel , Carnethon Mercedes , Dooley Erin , Ekelund Ulf , Evenson Kelly R , Pettee Gabriel Kelley P , Galuska Deborah A , Jefferis Barbara J , Kraus William E , Larson Martin , Lee I-min M , matthews charles , Newton Robert L , Omura John D , Palta Priya , Pieper Carl , Rees-Punia Erika , Pompeii Lisa , Rippon Brady , Spartano Nicole L , Ramachandran Vasan S , Yang Shengping , Fulton Janet E
Published: April 2024

Introduction:
The goal of 10,000 steps/day is widely promoted. There is limited evidence, however, of the number of steps/day associated with risk of developing cardiovascular disease (CVD).

Hypothesis:
We hypothesize a dose-response association between higher device-measured steps/day with lower CVD incidence.

Methods:
The Steps for Health Collaborative conducted a meta-analysis of seven prospective studies with device-measured steps/day and followed participants for CVD events. Participants without CVD at baseline were included. CVD was defined as coronary heart disease, stroke, and/or heart failure. Data were analyzed at the study level. Study-specific associations of quartiles of steps/day with incident CVD was assessed using Cox proportional hazards regression models and summarized using random effects meta-analysis. Models were adjusted for age, race/ethnicity, sex, body mass index, device wear time, and study-specific indicators for education or income, smoking, alcohol intake, blood pressure, dysglycemia, and hyperlipidemia. Study heterogeneity was assessed using I2 statistic.

Results:
The meta-analysis included 16,906 adults (mean age 62 years; 51% women), with median follow-up of 6.3 years (limits 2.9-10.7 years) and 1370 (8.1%) CVD events. Medians of study-specific steps/day were 1,951 (first quartile, Q1), 3,823 (second quartile, Q2), 5,685 (third quartile, Q3), and 9,487 (fourth quartile, Q4). Compared with Q1, summary hazard ratios for CVD were 0.83 (Q2, 95% confidence interval 0.72-0.95), 0.68 (Q3, 0.58-0.80), and 0.60 (Q4, 0.47-0.78) (Figure). There was low to moderate heterogeneity; I2 values were 0% for Q2, 2% for Q3, and 37% for Q4.

Conclusions:
Higher steps/day were associated with progressively lower risk of CVD. Monitoring and promoting steps/day can be a simple, easy to interpret metric used for clinician-patient communication and population health to reduce the risk of CVD.
Abstract 13918: Prognostic Implication of Mitral Valve Disease in Patients With Hypertrophic Cardiomyopathy
Authors: Kim Dae-Young , Seo Jiwon , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Shim Chi Young
Published: April 2024

Introduction:
Hypertrophic cardiomyopathy (HCM) is a genetic disorder affecting not only the myocardium, but also the mitral valve (MV) and its apparatus.

Hypothesis:
MV disease would have a prognostic implication in patients with HCM.

Methods:
We reviewed MV function and structure in the indexed echocardiograms of 1,185 HCM patients (60 ±14 years, men 67%) who were included in a single-center longitudinal HCM registry. Patients were classified as obstructive (n=104) or non-obstructive (n=1,081) HCM. Clinical outcomes were defined as a composite of cardiovascular death, heart failure hospitalization, MV surgery or septal myectomy, and heart transplantation.

Results:
Overall, 278 patients (23.5%) showed at least mild mitral regurgitation (MR) on their indexed echocardiogram (Figure 1-1). MR, systolic anterior motion (SAM), and mitral annular calcification (MAC) were more prevalent in patients with obstructive HCM than in those with non-obstructive HCM. During a mean of 7.0 ± 4.0 years’ follow-up, Kaplan-Meier plots revealed that patients with MR showed poorer clinical outcomes (21.6% vs.7.3%, log-rank p < 0.001) than those without MR (Figure 1-2). A multivariate Cox model revealed that MR was independently associated with clinical outcome (hazard ratio 1.57, 95% confidence interval 1.04-2.35, p=0.030) along with female sex, chronic kidney disease, atrial fibrillation, obstructive type HCM, and diastolic dysfunction.

Conclusions:
MV disease is not uncommon in patients with HCM. MR, SAM, and MAC are more prevalent in patients with obstructive HCM. The presence of MR is associated with a poor prognosis in patients with HCM.
Abstract 13925: Non-Linear Modelling of Social Determinants of Health to Predict Cardiovascular Mortality Risk
Authors: Tano Mauricio E , Valero Elizondo Javier , Cainzos Achirica Miguel , Javed Zulqarnain , Mortazavi Bobak , Khan Safi U , Nasir Khurram
Published: April 2024

Introduction:
Community-level social determinants of health (SDOH) can facilitate the identification of vulnerable populations with poor health outcomes.

Hypothesis:
We assess whether machine learning methods utilizing area-level SDOH indicators can identify populations at higher risk for CV mortality.

Methods:
144 SDOHs were extracted from the SDOH database compiled, at a county level, by the Agency for Healthcare Research and Quality between 2009-2018. The Person’s correlation coefficient between SDOH with CV mortality was used to select 12 key SDOH (p < 0.05) and linear and nonlinear models were tested to build a predictive model for CVD mortality rates per 100,000 people for each county from SDOH. Datasets were randomly split in 80/20 for training and validation, and the accuracy of the models was compared in terms of mean relative error (MRE).

Results:
SDOH related to income (median household income), poverty (fraction population with a poverty ratio more than 2.00), and educational attainment (high school, BSc, MSc, doctorate) were the principal factors affecting CV mortality. Factors related to race/ethnicity, living conditions (children living with grandparents), and physical infrastructure (median household value and fraction of mobile homes) were also included in the model. The most performant regression method is the Bayesian optimized artificial neural network (Figure). The performance of linear models (linear elastic-networks, MRE = 17.6%; linear regression, MRE = 38.8%) was inferior to nonlinear models. Among nonlinear models, optimized Bayesian feedforward neural networks OBFNN presented the best performance (MRE = 9.7%).

Conclusions:
We developed a county-level risk score for cardiovascular mortality using 12 SDOH including demographics, income and poverty, education, and physical infrastructure. Future work should look at extending beyond CVD mortality and combining this SDOH-based score for patient-level cardiovascular risk.
Abstract 13944: Young, Non-Hispanic Black Males and Females Exhibit Divergent Peripheral and Cerebral Vascular Reactivity
Authors: Martin Zachary T , Akins John D , Patik Jordan C , Curtis Bryon M , Campbell Jeremiah C , Olvera Guillermo , Brothers Robert
Published: April 2024

Introduction:
In the U.S., cardiovascular and cerebrovascular diseases (CVD) remain more prominent in non-Hispanic black individuals than in other populations. Across most racial/ethnic groups, total CVD prevalence is ~10% lower in females; however, total CVD prevalence in black females (BF) is similar to that of black males (BM). Conversely, BM have ~23% higher age-adjusted stroke mortality compared to BF, a pattern not seen in other groups. While the mechanisms behind these race-by-sex differences are multifactorial, vascular dysfunction likely contributes. Our group and others have demonstrated reduced brachial artery and cerebrovascular vasodilation in black versus white individuals, though much of this work did not specifically address sex differences. To this end, we have recently investigated and reported divergent mechanisms of reduced cutaneous microvascular function in BM and BF; however, more work is needed to better understand whether such findings extend to other vascular regions.

Hypothesis:
We tested the hypothesis that BF and BM would have divergent degrees of reduced peripheral and cerebral vasodilator responsiveness.

Methods:
Eleven BF and 15 BM (22 ± 4 vs. 23 ± 3 yrs) underwent testing for brachial artery flow-mediated dilation (FMD; conduit artery function) and post-occlusive reactive hyperemia (PORH; microvascular function), along with cerebrovascular reactivity (CVR) to rebreathing-induced hypercapnia.

Results:
FMD was greater in BF versus BM (9.10 ± 3.49 vs. 5.84 ± 2.78%;
P
= 0.02), even when normalized to baseline diameter or shear rate (
P
< 0.05 for both). BF had similar PORH when assessed as peak blood velocity (77.1 ± 19.9 vs. 79.4 ± 19.6 cm • s
-1
;
P
> 0.05) but lower peak blood flow (343.6 ± 169.8 vs. 495.4 ± 196.9 mL/min;
P
< 0.05) and blood flow AUC (133.6 ± 61.1 vs. 220.3 ± 130.7 mL;
P
= 0.04) relative to BM. CVR was greater in BF versus BM (0.024 ± 0.010 vs. 0.012 ± 0.006 cm • s
-1
• mmHg
-1
• mmHg
-1
;
P
< 0.01).

Conclusion:
These data suggest that young, BM have lower vascular reactivity than BF during some, but not all, tests of vascular function. More work in this area is needed to better understand the potential biological and social mechanisms influencing sex differences in vascular function and CVD risk in black individuals.
Abstract 13948: Patterns of Prescribing Sodium-Glucose Cotransporter-2 Inhibitors for Medicare Beneficiaries in the United States
Authors: Sangha Veer , Lipska Kasia , Lin Zhenqiu , Inzucchi Silvio E , McGuire Darren K , Krumholz Harlan M , Khera Rohan
Published: April 2024

Background:
Evidence from large randomized clinical trials supports the benefit of SGLT2is to improve cardiovascular and kidney outcomes in patients with type 2 diabetes mellitus (T2DM). In light of this evidence, prescription patterns of SGLT2i among US Medicare beneficiaries were evaluated.

Methods:
Antihyperglycemic medication prescribers were based on metformin prescribing in national Medicare part D prescriber data. The proportion of clinicians prescribing SGLT2i was assessed overall and across specialties in 2018, with changes assessed from 2014 to 2018. The relative use of SGLT2i was compared with other second-line antihyperglycemic medication classes, sulfonylureas and dipeptidyl peptidase-4 inhibitors (DPP4is), without known CV benefits.

Results:
Among the 232,523 unique clinicians who prescribed metformin for Medicare beneficiaries in 2018, 45,255 (19.5%) prescribed SGLT2i - varying from 72% of endocrinologists to 14% of cardiologists. Among clinicians who prescribed both sulfonylureas and SGLT2i, SGLT2i were prescribed to 33% (IQR 18%, 67%) the number prescribed sulfonylureas. Of 118,091 metformin-prescribing clinicians who also prescribed DPP4i, 39,511 (33.5%) used SGLT2i, with a median 50% SGLT2i prescription volume relative to DPP4i (IQR 33, 100). Between 2014-2018, the number of unique clinicians prescribing SGLT2i increased from 5-fold, from 9,048 in 2014 to 45,255 in 2018, and proportionate utilization of SGLT2i per prescriber relative to sulfonylureas also increased from 19% in 2014 to 33% in 2018 (P-trend <0.001).

Conclusions:
A vast majority of diabetes-treating clinicians did not prescribe SGLT2i to Medicare beneficiaries as recently as 2018. Moreover, prescriptions of sulfonylureas and DPP4is, which have no known cardiac or kidney benefits, were 3 and 2 times more frequent, respectively, than those of SGLT2is. These findings highlight opportunities to improve care and outcomes for patients with T2DM.
Abstract 13953: A Quality Improvement Initiative Increasing Early Discharges for Cardiovascular Surgery and Cardiology Patients on the Acute Care Cardiology Unit Was Associated With Reduced Hospital Length of Stay
Authors: Colyer Jessica H , Ring Lisa , Gallagher Sarah , Mullenholz Mary , Robison Jan , Rigney-Radford Kathleen M , Harahsheh Ashraf S
Published: April 2024

Introduction:
The discharge process in the acute care setting is a complex process composed of many parallel and sequential steps. Safe and timely discharges improve patient throughput. Early discharges off-load full ICUs and improve transitions to the outpatient setting. Review of our data demonstrated the majority of discharges occurred later in the day. We set out to improve our discharge times for cardiology and cardiovascular surgery (CVS) patients on our 26-bed inpatient acute care cardiology unit (ACCU)

Hypothesis:
Smart Aim: Increase the number of discharges between 6 am and 12 pm for cardiology and CVS patients on ACCU from 5 to 10 patients per month over 12 months and to sustain.

Methods:
We performed a Failure Mode Analysis to highlight the steps of the discharge process and identify opportunities for improvement. Our key drivers centered around education, documentation, and planning. Our interventions included: education of front-line staff, communication of discharge expectations, daily quality board rounds, hospital-wide collaboration emphasizing conditional discharges, and hospital IT improvements. Statistical process control charts were utilized to analyze the data.

Results:
The number of discharges between 6am and 12 pm more than doubled from a baseline of 5 (8%) to 12 (18%) patients per month with a centerline shift. As part of our process measures, appropriate conditional discharge usage linked to earlier discharges. Upgrades to our EMR discharge system further increased our timely discharges. Our efforts resulted in 22% reduction of hospital length of stay from 11.1 to 8.7 days without an increase in readmission rates suggesting that improved efficiency did not impact care quality.

Conclusions:
We successfully show how multidisciplinary collaboration and systems-based improvement can increase the number of safe, early discharges.