bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11686: The Myocardial Infarction and Cardiac Arrest Risk Calculator is an Accurate Discriminator of Major Adverse Events Following Elective Hip and Knee Surgery
Authors: Peterson Brandon , Ghahramani Mehrdad , Harris Stephanie , Suchniak-Mussari Kristen , Bedi Gurneet , Bulathsinghala Charles , Foy Andrew
Published: April 2024

Background:
The 2014 ACC/AHA guidelines on perioperative evaluation recommend differentiating patients at low-risk (<1%) versus elevated-risk (≥1%) for cardiac complications to guide appropriate preoperative testing. Among the tools recommended for estimating perioperative risk is the National Surgical Quality Improvement Program (NSQIP) Myocardial Infarction and Cardiac Arrest (MICA) risk calculator. The NSQIP MICA risk calculator showed good discriminating power when introduced in 2011, but has yet to be externally validated. The aim of the study was to investigate whether the NSQIP MICA risk calculator could accurately discriminate the incidence of major adverse events following elective hip and knee surgery.

Methods:
We reviewed 1,098 consecutive, elective orthopedic surgeries performed at Hershey Medical Center from January 2013 through December 2014, including 412 total hip replacements and 686 total knee replacements. Sufficient data were present to estimate risk using the NSQIP MICA risk calculator in 1,091 patients. Major adverse events were defined as myocardial infarction, cardiac arrest, or death within 30 days of surgery. A receiver operating characteristic curve was plotted from the estimated risk and adverse outcomes data.

Results:
Eight out of 1,091 procedures (0.7%) were complicated by a major adverse event. The mean estimated risk for adverse events using the NSQIP MICA risk calculator was 0.54% with a standard error of 0.018%. There was no significant difference (p=0.59) when comparing the observed versus expected incidence of major adverse events by chi-square test. The area under the curve (AUC) was determined to be 0.85 with a 95% confidence interval of 0.79-0.91 (see plot below).

Conclusion:
The NSQIP MICA risk calculator is a good discriminator of major adverse events following elective hip and knee surgery. Our study supports its use as a predictive tool for preoperative evaluation in this setting.
Abstract 11775: Initial US Experience With a Technician Supported Remote Interrogation System for Cardiac Implantable Electronic Devices in the Emergency Department and Perioperative Areas
Authors: Ahmed Imdad , Patel Amisha , Balgaard Timothy , Rosenfeld Lynda E
Published: April 2024

Introduction:
Patients (Pts) with cardiac implantable electronic devices (CIED)s often require device interrogation and interpretation in the Emergency Department (ED) or perioperative areas (OR) where personnel and equipment to perform this procedure are often not available. CareLink Express (CLE) (Medtronic, Inc.) is a new technician supported real time remote interrogation system designed to facilitate this process.

Objective:
The aim of this retrospective study was to assess the efficiency of CLE compared to traditional device management (TDM) and examine its findings.

Methods:
Data from the Medtronic deidentified database were used to assess CLE use and performance in the ED and OR from 01/2012 - 10/2014. All 7044 CLE transmissions from 136 US sites originating in the ED or OR, were compared to 217 TDM requests in 5 geographically diverse US sites where, prior to CLE, CIED interrogations and interpretations were performed by calling an industry representative to the ED or OR.

Results:
Compared to TDM, CLE resulted in a 78% reduction in the time to device interrogation and interpretation: (100±140 min to 22+14 min, P<0.0001). It improved response time and consistency in both the ED: 82+103 min to 23+18 min P<0.01, and OR: 127+181 min to 16.5+9.5 min P<0.0001. Overall, actionable events (arrhythmia, device/lead abnormalities) (AE) were found infrequently (ED AE: 9.9%; OR: 4.1%). AE were found in only 13.6% of Pts with a perceived shock and 6.5% of those presenting with syncope. AE were much more common in Pts with suspected abnormal device function (30.4%) or audible alerts (52.6%). Pts not enrolled in a remote monitoring system were almost 3 times more likely to have an AE identified than those enrolled in such a program (23.9% vs 8.2%, p<0.0001) and the presence of an older CIED system was associated with an increased likelihood of finding an AE with CLE use (7.4% in year 1 vs 31% after 10 years).

Conclusions:
The large number of Pts with CIEDs, and the opportunity to quickly and predictably identify the minority with high risk/life-threatening AE from the low risk majority, strongly support CLE as an attractive tool to save time, and improve resource utilization, especially in sites such as the ED and OR which are expensive and place a high priority on efficiency.
Abstract 11781: α1-syntrophin Mutation Identified in Drug-induced Long-QT Syndrome Increases Late Sodium Current
Authors: Choi Jong-Il , Wang Chaojian , Pitt Geoffrey S
Published: April 2024

Introduction:
Drug-induced long-QT syndrome (diLQTS) is an acquired disorder, often due to drug block of IKr, especially in genetically susceptible patients with subclinical mutations in the IKr-encoding KCHN2. Recent data suggest that the late sodium current (INa-L) augments the proarrhythmic effect of IKr inhibition, but few mutations in the cardiac NaV1.5 Na+ channel complex have been associated with diLQTS.

Hypothesis:
We hypothesized whether a novel SNTA1 mutation (p.E409Q) found in a patient with diLQTS increases INa-L, thereby providing a mechanism for diLQTs in this patient.

Methods:
Electrophysiological studies were performed in HEK293T cells co-expressing human NaV1.5/nNOS/PMCA4b with either wild-type (WT) or SNTA1 mutants (A390V-previously reported mutation in congenital LQTS; and E409Q), and in adult rat ventricular cardiomyocytes, which were infected with adenoviruses expressing either the WT or one of the two SNTA1 mutants.

Results:
In HEK293T cells, there was no significant difference in the peak INa densities at -30 mV among the WT and the mutants. However, INa-L (% of peak current) was increased in both mutants (0.58±0.10 in WT vs. 0.90±0.11 in A390V, p=0.048; vs. 0.88±0.07 in E409Q, p=0.023). In adult rat cardiomyocytes, peak INa densities at -40 mV were similar among the WT and the mutants. INa-L was significantly increased in E409Q-SNTA1, not in A390V-SNTA1 compared to WT-SNTA1 (0.49±0.14 in WT vs.0.94±0.23 in A390V, p=0.099; vs. 1.12±0.24 in E409Q, p=0.019).

Conclusions:
We demonstrated that a novel SNTA1 mutation is likely causative for diLQTS by augmenting INa-L. These data suggest the mutation of the NaV1.5-interacting α1-syntrophin is a potential mechanism for the genetic susceptibility in patients with diLQTS, thereby expanding the concept that mutations within congenital LQTS loci can cause diLQTS.
Abstract 11806: Not Glycemic Control Using Sitagliptin But Lipid Control is Associated With Change in Coronary Atherosclerosis in Patients With Type 2 Diabetes -A Serial Integrated Backscatter Intravascular Ultrasound Study
Authors: Nozue Tsuyoshi , Fukui Kazuki , Koyama Yutaka , Fujii Hiroyuki , Kunishima Tomoyuki , Hikita Hiroyuki , Hibi Kiyoshi , Miyazawa Akiyoshi , Michishita Ichiro
Published: April 2024

Introduction:
Dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherogenic effects in an animal model. However, clinical usefulness of DPP-4 inhibitors, particularly effects of these drugs on coronary atherosclerosis has not been fully evaluated.

Hypothesis:
We assessed the hypothesis that sitagliptin, a DPP-4 inhibitor, has beneficial effects on coronary atherosclerosis beyond its hypoglycemic action.

Methods:
A prospective, open-labeled, randomized multicenter study was performed at 6 Japanese centers. Twenty-eight patients with type 2 diabetes who have undergone elective percutaneous coronary intervention (PCI) were randomly assigned to either the sitagliptin group (group S) or control group (group C). Neither DPP-4 inhibitors nor glucagon-like peptide-1 analogues have been used in group C during study period. Non- PCI lesions were evaluated by integrated backscatter (IB)-intravascular ultrasound (IVUS) at the time of PCI and at 48-week follow-up. The primary end point was percentage change in plaque volume measured using grayscale IVUS and the secondary end point was changes in plaque compositions measured using IB-IVUS.

Results:
Grayscale IVUS analysis demonstrated that plaque volume tended to be decreased in both groups (group S: -1.7%; group C: -3.2%), but could not reach statistically significance. In addition, percentage changes in plaque volume did not differ between the 2 groups. On IB-IVUS analysis, a significant decrease in the lipid component (group S: from 200.1 to 179.8 mm3, p=0.02; group C: from 298.3 to 256.6 mm3, p=0.1) and an increase in the calcified component (group S: from 2.1 to 3.2 mm3, p=0.06; group C: from 2.3 to 4.8 mm3, p=0.04) were observed. Univariate and multivariate regression analyses showed that sitagliptin use did not correlate with a decrease in the lipid component, whereas percentage change in serum non high-density lipoprotein cholesterol (HDL-C) was an independent and significant predictor associated with change in the lipid component (β=0.454, p=0.04).

Conclusions:
Sitagliptin had no effects on coronary atherosclerosis in patients with type 2 diabetes. Not glycemic control but lipid control, particularly a decrease in non-HDL-C was associated with the reduction in lipid component.
Abstract 11924: Iso-osmolar Contrast Media Superior in Chronic Kidney Disease Patients Undergoing Coronary Angiography: A Meta Analysis of Current Evidence
Authors: Pandya Bhavi P , Gaddam Sainath , Pandya Shreya , El-Sayegh Suzanne , Kandov Ruben , Lafferty James
Published: April 2024

Background:
Coronary angiography is one of the most common causes of contrast-induced nephropathy. Adequate hydration and keeping the volume of contrast media to a minimum are class 1b recommendations for preventing contrast-induced nephropathy. Current data are insufficient to justify specific recommendations about iso- and low-osmolar contrast media, and no specific guidelines on use of different contrast media have been provided by ACCF/AHA/SCAI.

Objective:
We performed a systematic review and meta-analysis comparing the renal safety of iso-osmolar to low-osmolar contrast media in chronic kidney disease patients with stage 3 and above who underwent coronary angiography.

Methods:
Randomized trials comparing iso- to low-osmolar contrast media in chronic kidney disease stage 3 and above patients undergoing coronary angiography, and reporting contrast-induced nephropathy by a rise in creatinine of 25% from baseline were included in the analysis. Meta-analysis was done using a fixed effects size model and results were expressed in terms of Odds Ratio (OR) and 95% Confidence Interval (CI) after evaluating for interstudy heterogeneity using I
2
.

Results:
A total of 2,007 patients were included in 7 trials, in which 1,019 patients received iso-osmolar and 988 received low-osmolar contrast media. When compared to low-osmolar contrast media, use of iso-osmolar contrast media showed statistical significant benefit in terms of preventing contrast-induced nephropathy in chronic kidney disease patients (OR=0.75, [CI: 0.58, 0.96], p=0.02, I
2
=64%).

Conclusion:
In chronic kidney disease patients with stage 3 and above undergoing coronary angiography, use of iso-osmolar contrast media showed benefit in terms of preventing contrast-induced nephropathy compared to low-osmolar contrast media.
Abstract 11930: Sex Differences in Cardiac Troponin and the Risk of Death or Major Cardiovascular events in Men and Women With Diabetes and Coronary Artery Disease
Authors: Everett Brendan M , Brooks Maria , Vlachos Helen , Chaitman Bernard R , Frye Robert L , Bhatt Deepak L
Published: April 2024

Background:
Circulating cardiac troponin T concentrations are higher in men than in women, but the biological causes and clinical implications of this observation are poorly understood.

Methods and Results:
We measured cardiac troponin T with a high-sensitivity assay (hsTnT) in 684 women and 1601 men with type 2 diabetes (T2D) and stable ischemic heart disease (SIHD) who were enrolled in the BARI 2D trial. Median (IQR) hsTnT was higher in men [12.4 ng/L (8.7-20.8)] than in women [9.1 ng/L (6.4-15.6); P<0.0001] and a higher proportion of men (43.6%) than women (29.1%) were above the current established upper reference limit of 14 ng/L (P<0.0001). Sex remained a significant predictor of natural log normalized hsTnT after adjusting for a wide array of covariables, including age, race, insulin use, renal function, ejection fraction, and HbA1c. Within quintiles of hsTnT measured at baseline, the 5-year incidence of the composite cardiovascular outcome of myocardial infarction, stroke, heart failure, or death was consistently higher in women than in men (Figure 1). In sex-stratified Cox models adjusting for possible confounders, the increase in the relative risk of the composite endpoint across quintiles of hsTnT appeared similar in men and women (Figure 2).

Conclusions:
In the BARI 2D trial, women have lower baseline hsTnT concentrations, but higher absolute risk of myocardial infarction, stroke, heart failure, or death for a given concentration of hsTnT. These data raise the question of whether sex-specific cutoffs for cardiac troponin T should be considered.
Abstract 11944: Association of Heavy Alcohol Consumption With Risk of Heart Failure Stratified by Patient Characteristics
Authors: Whitman Isaac R , Agarwal Vratika , Dukes Jonathan W , Vittinghoff Eric , Dewland Thomas A , Marcus Gregory M
Published: April 2024

Introduction:
While cardiac systolic dysfunction secondary to chronic abuse of alcohol is well described, some evidence suggests a cardiovascular benefit of moderate alcohol consumption. It remains unclear if heavy alcohol consumption predicts congestive heart failure (CHF) in the general population. In addition, the patient characteristics that might influence this relationship remain unknown.

Methods and Results:
We randomly selected 1 million adults from the California Healthcare Cost and Utilization Project database (capturing all emergency department, ambulatory procedural, and inpatient healthcare encounters) from January 1, 2005 to December 31, 2009. After exclusions for missing demographic information (N=72,301, 7%) and prevalent CHF at study entry (N=69,512, 7%), 858,187 patients were included in the analysis. Analysis variables were defined using ICD-9 codes. During study follow-up, 4% (N=33,046) were coded with alcohol abuse and 12% (N=106,655) developed incident CHF. The mean age was 52 ± 21 years, 35% (N=299,884) were men, and 45% (N=384,204) were white. After adjustment for age, gender, race, hypertension, diabetes, coronary artery disease, chronic kidney disease, valvular heart disease, dyslipidemia, smoking, obesity, obstructive sleep apnea, and income, alcohol abuse was associated with a 70% increased risk of incident CHF (hazard ratio 1.69, 95%CI 1.49-1.91, P<0.001). This relationship was especially strong among younger individuals and those without hypertension (
Figure
).

Conclusions:
Alcohol abuse was associated with incident CHF in this diverse, population-based cohort. Interaction analyses suggest that the mechanism linking alcohol abuse to development of heart failure may resemble those intrinsic to age related comorbidities and hypertension. Younger individuals and those without hypertension may be disproportionately prone to the myocardial toxic effects of alcohol.
Abstract 11968: Uninterrupted Chest Compressions does not Improve Hemodynamics During and After Cardiopulmonary Resuscitation in Asphyxiated Newborn Pigs
Authors: Solevåg Anne Lee , Schmölzer Georg M , O’Reilly Megan , Lu Min , Lee Tze-Fun , Fortin-Pellerin? Etienne , Hornberger Lisa , Cheung Po-Yin
Published: April 2024

Introduction:
Since asphyxia is the most common cause of a need for newborn cardiopulmonary resuscitation (CPR) the primary focus of CPR should be effective ventilation. Any intervention that interferes with ventilation should be introduced with caution. Thus, in newborn CPR it is recommended that chest compressions (CC) and ventilation be synchronized with a pause after every 3rd CC to deliver one effective ventilation, i.e. a CC to ventilation (C:V) ratio of 3:1. However, this recommendation is based on physiological plausibility, not scientific evidence. In adult CPR uninterrupted CC has been shown to improve hemodynamics including coronary perfusion pressure (CPP) and outcomes.

Hypothesis:
In a newborn piglet model, we hypothesized that continuous CC and asynchronous ventilation (CCaV) would improve CPR hemodynamics and time to return of spontaneous circulation (ROSC) vs. 3:1 C:V CPR.

Methods:
Thirty-two intubated piglets (1-3d old) were instrumented with a catheter in the left common carotid artery, asphyxiated until cardiac arrest and randomized to 3:1 C:V CPR or CCaV (n=16 in each group). In both groups, manual CC were performed and a metronome was used to help achieve 120 events (90 CC and 30 assisted ventilations)min-1. CPR characteristics and time to ROSC were compared between groups with the Mann-Whitney U test. Lactate was determined from homogenized left ventricle (LV) tissue collected 4 h after ROSC.

Results:
At cardiac arrest, median (IQR) arterial pH was 6.6 (6.5-6.9), paCO2 78 (48-97) mmHg and lactate 18 (15-19) mmol/L with no differences between groups. Characteristics of CPR and post-CPR recovery are presented in Table 1.

Conclusions:
Despite a modestly higher number of CCmin-1 CCaV did not improve DBP, a proxy for CPP during CPR, or ROSC. Mean arterial blood pressure after ROSC was slightly lower and LV lactate higher following CCaV vs. 3:1 C:V CPR. The results confirm the assumption that extrapolating evidence from adults to newborns is inappropriate.
Abstract 11996: The Impact of Left Ventricular Diastolic Dysfunction on Instantaneous Wave-Free Ratio in Intermediate Coronary Stenosis
Authors: Ri Tonre , Arashi Hiroyuki , Yamaguchi Junichi , Shibahashi Eiji , Itani Ryosuke , Shimazaki Kensuke , Otsuki Hisao , Haruki Shintaro , Nakao Masashi , Kamishima Kazuho , Jujo Kentaro , Minami Yuichiro , Hagiwara Nobuhisa
Published: April 2024

Background:
Instantaneous wave-free ratio (iFR) is a new vasodilator-free index of the functional severity of coronary stenosis and reported to have a similar feature to coronary flow reserve (CFR) that is considered to reflect not only resistances of an epicardial stenosis but also microvascular resistances in myocardium. Previous studies reported that CFR was impaired in patients with left ventricular (LV) diastolic dysfunction which is thought to have an impact on microvascular circulation. However, there was no report examining the impact of LV diastolic dysfunction on iFR. Accordingly, the purpose of this study was to assess the relationship between iFR and LV diastolic dysfunction in comparison with fractional flow reserve (FFR).

Method and Results:
We examined consecutive 76 patients (with 107 stenosis) whose iFR, FFR and E/e’ were measured simultaneously. Patients with hemodialysis or left ventricular hypertrophy (defined as left ventricular mass index more than 116g/m2 (male) or 96g/m2 (female) in echocardiography) were excluded. LV diastolic dysfunction in the present study was defined as E/e’ more than 15. The mean age of patients with LV diastolic dysfunction (n=18, mean E/e’=19.3 ± 6.3) was higher than patients without LV diastolic dysfunction (n=58, mean E/e’= 10.1 ± 6.2). Other patients’ characteristics are shown in table 1. The mean iFR values in patients with LV diastolic dysfunction was significantly lower than that in patients without LV diastolic dysfunction, despite no significant differences were observed in the mean FFR values and % diameter stenosis (Table 2). iFR showed negative correlation with E/e’ (r=0.31, p=0.0012) (Figure 1), whereas, there was no correlation between FFR and E/e’ (data not shown).

Conclusion:
Our present results suggested that LV diastolic dysfunction affect the iFR values, but not FFR, in intermediate coronary stenosis. In patients with LV dysfunction, iFR may overestimate the severity of coronary stenosis.
Abstract 12087: KCa3.1 Channels Support Resting Potential and Proliferative Function During Store-Operated Ca
2+
-Entry in c-kit
+
Endogenous Cardiac Stem Cells
Authors: Vigneault Patrick , Naud Patrice , Davis Darryl R , Nattel Stanley
Published: April 2024

Introduction:
Adult hearts contain c-kit
+
endogenous cardiac stem cells (eCSCs). Cultured eCSCs express a wide range of ion channels, but cell culture is known to affect phenotype. Here we defined ion currents in freshly isolated c-kit
+
eCSCs and their potential functional role.

Methods:
eCSCs isolated from healthy and heart failure (HF, ventricular tachypacing X 2 wks) dog hearts were magnetically purified with c-kit antibodies. Ion currents and membrane potential were recorded with patch clamp.

Results:
Contrary to cultured c-kit
+
eCSCs, ion currents were barely detectable with Ca
2+
i
buffered (Fig A). Free Ca
2+
i
activated prominent I
KCa3.1
(TRAM34 sensitive, Fig B) in 82% of cells. I
KCa3.1
was reduced in eCSCs isolated from HF dogs (Fig C), along with corresponding KCNN4 mRNA (Fig D). Under perforated patch to maintain spontaneous physiological [Ca
2+
]
i
, eCSCs had a membrane potential (V
mem
) of -73±10 mV. Ca
2+
i
depletion with nominally 0 mM [Ca
2+
]
o
strongly depolarized the membrane. After passive Ca
2+
i
depletion, store-operated channel (SOC) mediated Ca
2+
entry (SOCE) caused a robust V
mem
hyperpolarization (from -21±4 to -79±7 mV, p<0.001). The SOCE effect on V
mem
was substantially reduced by both 2-APB (SOC inhibitor) and TRAM34 (Fig E). Inhibiting KCa3.1 (TRAM34, 0.1 μM) or SOCs (2-APB, 50 μM) in culture decreased c-kit
+
eCSCs proliferation by 21% (p<0.05) and 55% (p<0.001) respectively.

Conclusions:
In contrast to cultured eCSCs, voltage-dependent ion currents are virtually absent from freshly isolated c-kit
+
eCSCs. I
KCa3.1
is prominent and maintains V
mem
in the face of substantial Ca
2+
entry from SOCs. This Ca
2+
entry would normally depolarize the cell, reduce the gradient for Ca
2+
entry and turn off the Ca
2+
signal. We hypothesize that the Ca
2+
-mediated KCa3.1 K
+
-conductance increase is necessary to maintain V
mem
in the face of the Ca
2+
entry that activates eCSC proliferation, and that KCa3.1 channels may therefore play an important role in eCSC function.
Abstract 12113: Early Right Ventricular Response to Cardiac Resynchronization Therapy: Impact on Clinical Outcomes
Authors: Stolfo Davide , Tonet Elisabetta , Merlo Marco , Barbati Giulia , Gigli Marta , Pinamonti Bruno , Ramani Federica , Zecchin Massimo , Sinagra Gianfranco
Published: April 2024

Introduction:
Right ventricular (RV) dysfunction has been associated with a worse outcome in heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT). However, evidences on the RV response to CRT are controversial and there are no data regarding the early effects of CRT on RV function (RVF).

Hypothesis:
We sought to investigate whether CRT favorably influences the RVF acutely after implantation, impacting on long-term outcomes.

Methods:
Patients who successfully underwent CRT implantation from January 2005 to January 2014 were retrospectively analyzed. RV dysfunction was defined by a RV-fractional area change<35%. Post-procedural echocardiographic evaluation was performed at a median time of 2 days (IQR 1-6). Primary end-point was a composite of all-cause mortality and urgent heart transplantation.

Results:
A total of 194 patients with available pre- and post-procedural RVF assessment were included. Sixty-two (32%) presented an impaired RVF before procedure. Of them, 32% promptly normalized RVF following CRT. This occurred in parallel with a large improvement in pulmonary arterial pressure, mitral regurgitation, E/E’ ratio and diastolic function. Pre-implantation independent predictors of early RVF normalization were left-bundle branch block (p=0.034) and higher systolic blood pressure (p=0.026). Improvement in RVF was independently associated with a better long-term prognosis at multivariable analysis (HR 0.124; 95% CI 0.016-0.966, p=0.04), significantly increasing the accuracy of the long-term risk stratification compared to the baseline Cox model (p=0.04 at 48 months and p=0.048 at 96 months).

Conclusions:
Acute normalization of RVF can be observed after CRT along with hemodynamic improvement, resulting as independent predictor of transplant-free survival.
Abstract 12295: Utilization of Whole-Exome Sequencing to Identify Causative Mutations in Familial Congenital Heart Disease
Authors: LaHaye Stephanie , Corsmeier Don , Bowman Jessica L , Fitzgerald-Butt Sara , Zender Gloria , Bosse Kevin , McBride Kim L , White Peter , Garg Vidu
Published: April 2024

Congenital heart disease (CHD) is the most common type of birth defect, affecting ~8 out of every 1,000 live births, but there remains a limited understanding of the etiology for the majority of cases of CHD. Familial and population based studies have identified a strong genetic component to CHD, and familial cases of almost every type of CHD have been reported. The goal of this study was to identify pathogenic segregating variants in multiplex CHD families by whole-exome sequencing (WES). Target capture was performed using the Agilent SureSelectXT Target Enrichment kit, followed by WES on an Illumina HiSeq2500, on members from 9 families with Mendelian inherited CHD. Sequence alignment, post alignment processing, variant calling, and genotyping was performed with the Churchill pipeline. Tertiary analysis and annotation consisted of identifying rare (<1% mean allele frequency in the population) segregating variants, prioritizing by matching to a CHD gene list, and predicting pathogenicity via 12 different utilities. This strategy utilized a list of 69 CHD genes selected under strict criteria and allowed for prioritization of the variants. Predicted pathogenic mutations were identified in 3 of the 9 families. A splice donor site mutation was identified in
MYH11
(c.4599+1delC) in a family with autosomal dominant patent ductus arteriosus that is predicted to cause a 71 amino acid deletion, affecting functionality of the coiled-coil tail domain. A
GATA4
mutation, p.G115W
,
was identified in a family with autosomal dominant atrial septal defects (ASD) and is predicted to affect the transactivation ability of
GATA4
. A p.I263V mutation in
TLL1
was identified in a family with autosomal dominant ASD; as this mutation was located in the astacin-like metalloprotease catalytic domain it is predicted to affect the enzymatic efficacy of
TLL1
. In summary, our findings demonstrate the clinical utility of WES to successfully identify causative mutations in familial CHD and support the use of a CHD candidate gene list to allow for a more streamlined approach that enables rapid prioritization and identification of pathogenic variants from large WES data sets.
Abstract 12329: Novel High-Throughput ELISAs to Measure ApoC-III on ApoB-100, ApoA-I and Lp(a): Reduction in Lipoprotein-Associated ApoC-III Levels With Volanesorsen (ISIS-APOC-IIIRx) Antisense Therapy to ApoC-III in a Phase 2 Randomized Trial
Authors: Yang Xiaohong , Lee Sang-Rok , Choi Yun-Seok , Alexander Veronica J , Yang Qingqing , Witztum Joseph L , Tsimikas Sotirios
Published: April 2024

Background:
Elevated apolipoprotein C-III (APOC-III) levels are associated with hypertriglyceridemia and are causally associated with cardiovascular events. ApoC-III present on LDL and HDL particles predicts increased cardiovascular risk.

Objectives:
Traditional methods to detect apoC-III on LDL or HDL density fractions utilize labor-intensive immunoprecipitation of apoC-III and/or ultracentifugation methods. We developed high-throughput sandwich chemiluminescent ELISAs to detect apoC-III on individual lipoproteins in plasma.

Methods:
Monoclonal antibodies MB47, LPA4 and goat anti-human apoA-I were plated to capture apoB-100, Lp(a) and apoA-I lipoproteins, respectively, and the content of apoC-III on each was detected with an anti-apoC-III monoclonal antibody. ApoC-III-apoB-100, apoCIII-Lp(a) and apoC-III-apoA-I complexes were measured at baseline and day 57, 92 and 176 in 77 patients with hypertriglyceridemia treated with 100, 200, 300mg volanesorsen (ISIS-APOC-IIIRx), a generation 2.0+ antisense drug to apoC-III or placebo, for 85 days.

Results:
The ELISAs detected apoC-III-apoB, apoC-III-apoA-I and apoCIII-Lp(a) with high signal-to-noise ratios. Compared to placebo, a dose-response effect was noted with volanesorsen at day 92 with 84.2±10.1%, 80.7±16.6%, and 80.7±14.3% reductions in ApoC-III-apoB, apoCIII-Lp(a) and apoC-III-apoA-I, respectively (300 mg dose; p<0.001 for all), and return to baseline by day 176. Strong correlations in all assay measures were noted with changes in total plasma apoC-III and triglycerides.

Conclusions:
Novel high-throughput ELISAs were developed to detect lipoprotein-associated apoC-III, including for the first time on Lp(a). Volanesorsen uniformly lowers apoC-III on apoB-100, Lp(a) and apoA-I. Ongoing studies with cardiovascular endpoints will define whether lipoprotein-associated apoC-III biomarkers have prognostic utility and/or can be targets of apoC-III-directed therapy.
Abstract 12336: Non-invasive Screening for Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis
Authors: Alkukhun Laith , Ahmed Mostafa , Baumgartner Manfred , Budev Marie , Dweik Raed , Tonelli Adriano
Published: April 2024

Introduction:
Pulmonaryhypertension (PH) is a common complication of idiopathic pulmonary fibrosis (IPF) that is associated with poor prognosis. Screening for PH in IPF patients proves to be challenging.

Hypothesis:
We hypothesized that combining several non-invasive studies can predict the presence of PH in IPF patients.

Methods:
We included 235 IPF patients who underwent right heart catheterization (RHC) as part of the lung transplant evaluation. We measured ECG and echocardiographic variables as well as the pulmonary artery (PA) diameter and ascending aorta (AA) diameters on chest CT. We recorded results of arterial blood gases (ABG), pulmonary function (PFT) and 6-min walk tests (6MWT).

Results:
Several variables were predictors of PH in IPF patients in univariate models including arterial oxygenation, 6MWT distance, worse right ventricular (RV) function, the QRS axis, FVC/DLCOc ratio, PA/AA diameter ratio and estimated RV systolic pressure. In multivariate analysis, RV function and PA/AA ratio remained predictors of PH (c-statistics 0.75 (0.65-0.84), accuracy 71.4%). Similarly, RV function, PA/AA ratio and QRS axis were independent predictors of precapillary PH (c-statistics 0.86 (0.76-0.92), accuracy 84.2%). A combination of PA/AA diameter ratio <1.1, a QRS axis <90° and normal RV function showed a negative predictive value of 85% for precapillary PH.

Conclusions:
There are significant differences in ECG, echocardiographic, chest CT, PFT and ABG parameters between IPF patients with and without PH. However, these noninvasive tests alone or combination are not accurate enough for PH screening in IPF.
Abstract 12348: Different Outcomes by First Documented Rhythm After Witnessed Out-of-Hospital Cardiac Arrest in Children
Authors: Hara Masahiko , Hayashi Kenichi , Kitamura Tetsuhisa
Published: April 2024

Background:
Preventing the tragedy of pediatric out-of-hospital cardiac arrest (OHCA) is an important public health problem, and further accumulation of evidence is needed to improve the outcomes after pediatric OHCA. However, little evidence is available about the prognostic differences by first documented rhythm.

Methods and Results:
We enrolled 3968 young (< 18 years old) witnessed OHCA patients between 2005 and 2012 from a prospective nationwide population-based cohort database in Japan. We assessed and compared the neurologically favorable one-month survival defined as Glasgow-Pittsburg cerebral performance category 1 or 2 by first documented rhythm (pulseless ventricular tachycardia/ventricular fibrillation [pVT/VF], pulseless electrical activity [PEA], and asystole). The number of OHCA patients with pVT/VF, PEA, and asystole were 556, 1249, and 2163, respectively. The proportion of overall neurologically favorable one-month survival in patients with pVT/VF, PEA and asystole were 36.5%, 5.0%, and 1.8%, respectively in all study population and 73.8%, 27.7%, and 13.8%, respectively in patients who achieved prehospital ROSC. Figure shows the relationship between time from collapse to first cardiopulmonary resuscitation (CPR) and the endpoint in total population with estimated probabilities of the endpoint (line) and the respective 95% confidence intervals (bands). The proportion of asystole increased as the time from collapse to CPR delayed whereas those of pVT/VF and PEA decreased (Trend p<0.001). Earlier initiation of CPR after pediatric OHCA resulted in higher achievement rate of prehospital ROSC (adjusted odds ratio 0.97, 95% confidence interval 0.95-1.00, p=0.025) which showed much better prognoses than those in total study population.

Conclusions:
The pediatric OHCA outcome differed by the type first documented rhythm. Shortening of time to first CPR is crucial for improving outcomes after pediatric OHCA.
Abstract 12461: Strength of Physician Recommendation Increases Home-based Exercise Participation in Patients With Coronary Heart Disease
Authors: Tintle Nathan L , Clark Jacob A , Dunn Maureen , Buursma Madison P , DeVon Holli A , Dunn Susan L
Published: April 2024

The majority of individuals with coronary heart disease (CHD) do not meet current exercise guidelines and less than half enroll in hospital-based cardiac rehabilitation (CR) exercise programs. Strength of physician referral can positively affect participation in a hospital-based CR program, but it is unknown how the strength of physician referral may impact home exercise in patients with CHD. It was hypothesized that the strength of physician recommendation would positively impact home exercise participation. A total of 251 patients with CHD completed the Cardiac Rehabilitation Exercise Participation Tool 3 months after hospital discharge. Participants were typical of the CHD population, with 165 being male (65.7%) and a mean age of 65 years (SD= 9.8). Of the total sample, 188 (75%) reported receiving physician referral for home exercise, with the mean strength of the referral being 2.9 (SD= 1.9) on a scale of 0 (none) to 5 (strong). One hundred twenty-two patients (48.6%) reported exercising 3 or more days a week at home. Logistic regression was used to evaluate the impact of the strength of physician referral on the likelihood that patients would participate in home exercise after hospital discharge. Covariates included age, sex, race, marital status, employment status, education level, insurance type, cardiac procedure type, history of CHD, history of depression, functional status, and exercise prior to hospitalization. Increased strength of physician referral was predictive of increased home exercise participation (adjusted OR 1.5, 95% CI [1.3-1.7], p< 0.001). Male sex was also predictive, with 58.4% of males, as compared to 40% of females, reporting home exercise (adjusted OR 1.9, 95% CI [1.0-3.6], p= 0.049). Exercise prior to hospitalization was a final predictor, with 58.4% of prior exercisers, as compared to 41.7% of non-exercisers, reporting home exercise participation after hospital discharge (adjusted OR 2.0, 95% CI [1.1-3.6], p= 0.03). These findings demonstrate the beneficial effect of a strong physician recommendation for home-based exercise in patients with CHD. Physician referral is particularly important for women and patients who have not exercised before a cardiac event, as they reported doing less exercise after discharge home.
Abstract 12511: Exercise Stress Test and Myocardial Perfusion Imaging Have Limited Diagnostic Reliability in Detecting Coronary Abnormalities in Children After Arterial Switch Operation for Transposition of the Great Arteries
Authors: Tsuda Takeshi , Bhat Abdul M , Baffa Jeanne M , Radtke Wolfgang , Robinson Bradley
Published: April 2024

Background:
Exercise stress test (EST) and myocardial perfusion imaging (MPI) are common non-invasive modalities to screen for occult myocardial ischemia, but their sensitivity and specificity in children are unknown.

Hypothesis:
EST and MPI have limited sensitivity and specificity in detecting occult myocardial ischemia in children.

Patients and Methods:
We retrospectively reviewed EST, MPI, and coronary angiogram in asymptomatic patients after arterial switch operation (ASO) for d-transposition of the great arteries (TGA) and examined the sensitivity and specificity of EST/MPI in detecting coronary abnormalities. Positive ECG findings for exercise-induced ischemia included ST-T depression > 2mm and exercise-induced ventricular ectopies. Positive MPI is defined as a perfusion defect. Data are shown as mean ± SD.

Results:
Thirty asymptomatic patients (20 male/10 female; 23 with intact ventricular septum and 7 with ventricular septal defect; ages 12.5 ± 4.4 years) had EST and 26 had simultaneous MPI. Respiratory quotient was 1.11 ± 0.07 and maximum oxygen consumption was 80.7 ± 15.0% predicted, suggesting mildly diminished aerobic fitness level. There was no exercise-induced arrhythmia. Twenty two patients had coronary angiogram (Table 1). Four patients with positive EST and/or MPI were confirmed to have coronary abnormalities by coronary angiogram, whereas 4 patients revealed variable degree of coronary obstruction despite negative EST/MPI including 1 patient who later developed life-threatening ventricular fibrillation. Three patients with positive EST or MPI showed no coronary abnormalities.

Conclusions:
A combination of EST and MPI has low sensitivity (50%; 4/8) and moderate specificity (79%; 11/14) in detecting coronary abnormalities after ASO. Thus, we recommend performing coronary angiography or equivalent coronary investigation in addition to EST/MPI in children after ASO to detect coronary abnormalities and myocardial ischemia.
Abstract 12552: A Novel Predictor of Weight Change During Hospitalization in Patients With Acute Heart Failure Syndromes in the Emergency Department
Authors: Otomo Fumie , Endo Mitsuaki , Akiyama Eiichi , Matsuzawa Yasushi , Konishi Masaaki , Suzuki Toru , Koga Shintaro , Saigo Sae , Inoue Mitsuho , Hibi Kiyoshi , Himeno Hideo , Umemura Satoshi , Kimura Kazuo
Published: April 2024

Introduction:
Recent data showed acute heart failure syndromes (AHFS) could occur without weight gain, and often be triggered by rather a redistribution of fluids to the lungs without systemic congestion. In this subtype of AHFS, excessive diuretic and vasodilator therapy as first-line decongestion therapy in the emergency department (ED) may lead to dehydration and hypotension, subsequently resulting in serous organ hypoperfusion. Therefore, an accurate assessment of body fluid status is essential in AHFS.

Methods:
We studied 196 consecutive AHFS patients (77±12 years, 54% men, left ventricular ejection fraction 37±15%), who discharged after restoration of clinical stability (length of hospital stay 18±8 days). We collected clinical, laboratory, imaging and weight information. Measurements of total body water (TBW) and extracellular water (ECW) using bio-impedance analysis (BIA) were performed immediately at admission to the ED. Patients were divided into 2 groups according to the median % weight change (%WC) during hospitalization.

Results:
Weight and brain natriuretic peptide levels significantly decreased following decongestion therapy (from 59.0±14.3 to 52.9±12.9 kg, and from 779 [508-1289] to 285 [151-547] pg/ml, respectively, both p<0.001). High-%WC group (≥9.4%) had lower systolic blood pressure (159±35 vs. 171±40 mmHg), and higher prevalence of day-time admission (79 vs. 54%), peripheral edema (82 vs. 43%) and pleural effusion on chest radiography (88 vs. 71%), and larger inferior vena cava diameter (20±5 vs. 17±5 mm) and lower tricuspid annular plane systolic excursion (14±4 vs. 16±4 mm) on echocardiography, and higher estimated glomerular filtration rate (eGFR) (58±29 vs. 46±21 ml/min/1.73m2), lower serum total protein level (6.5±0.6 vs. 6.8±0.7 g/dl), and higher ECW/TBW (0.423±0.015 vs. 0.405±0.013) compared with low-%WC group (p<0.01 for all). Multiple linear regression analysis revealed that pleural effusion, eGFR, and ECW/TBW were significantly associated with %WC. ECW/TBW correlated most strongly with %WC (r=0.61, p<0.0001).

Conclusions:
ECW/TBW helps enable emergency physicians to implement goal-directed treatment more rapidly and appropriately avoiding both dehydration and volume retention in AHFS.
Abstract 12610: Vascular Function and Vascular Structure are impaired in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Kishimoto Shinji , Higashi Yukihito , Noma Kensuke , Nakashima Ayumu , Hidaka Takayuki , Maruhashi Tatsuya , Kajikawa Masato , Iwamoto Yumiko , Iwamoto Akimichi , Oda Nozomu , Aibara Yoshiki , Kihara Yasuki
Published: April 2024

Background:
Endothelial dysfunction and abnormal vascular structure may be involved in the pathogenesis of chronic heart failure. The purpose of this study was to evaluate simultaneously the vascular dysfunction and structure in patients with heart failure with preserved ejection fraction (HFpEF).

Methods and Results:
We measured flow-mediated vasodilatation (FMD) and nitroglycerine-induced vasodilation as indices of vascular function and intima-media thickness (IMT) as an index of vascular structure of brachial artery in 116 patients with HFpEF (66 men and 50 women; mean age, 61±14 yr) and 64 patients without HF (48 men and 16 women; mean age, 50±17 yr). There were significant differences in age, sex, blood pressure, N-terminal pro-brain natriuretic peptide, estimated glomerular filtration and prevalence of diabetes mellitus between the 2 groups. FMD was significantly smaller in patients with HFpEF than in patients without HF (3.6±2.5% versus 5.2±3.1%, P<0.001). Nitroglycerin-induced vasodilation was significantly smaller in the patients with HFpEF than in patients without HF (11.3±5.0% versus 13.3±4.9%, P=0.015). Brachial artery IMT were significantly larger in the patients with HFpEF than in patients without HF (0.34±0.07 mm versus 0.29±0.08 mm, P<0.001). After adjustment for age and sex, hypertension, diabetes mellitus, the associations remained significant between HFpEF and FMD (hazard ratio, 1.18; 95% confidence interval, 1.02-1.37: P=0.025) and brachial artery IMT (hazard ratio, 0.93; 95% confidence interval, 0.88-0.99: P=0.031) but not nitroglycerine-induced vasodilation (hazard ratio, 1.05; 95% confidence interval, 0.98-1.13: P=0.17).

Conclusions:
These findings suggest that both endothelial dysfunction and abnormal vascular structure contribute to the pathogenesis of HFpEF. Endothelial function and vascular structure may be potential therapeutic targets for HFpEF.
Abstract 12647: Race and Gender Differences in Post-Myocardial Infarction Angina Frequency and Rehospitalization Risk
Authors: Hess Connie N , McCoy Lisa A , Doll Jacob , Cohen David J , Peterson Eric D , Wang Tracy Y
Published: April 2024

Background:
Race and gender disparities in in-hospital treatment and outcomes of acute myocardial infarction (MI) patients have been described, yet little is known about race and gender differences in post-MI angina frequency and rehospitalization risk.

Methods:
Among 11,595 MI patients treated with PCI during the index hospitalization who survived the first year post-discharge in the TRANSLATE-ACS study (2010–2012), we examined 6-week and 1-year angina frequency stratified by race and gender. We used multivariable logistic regression to assess factors associated with 1-year unplanned rehospitalization and assessed for interactions between angina status, race, and gender.

Results:
Among 11,595 patients, there were 7,726 (66.6%) white males, 2,816 (24.3%) white females, 616 (5.3%) black males, and 437 (3.8%) black females. Comorbidities, including hypertension, diabetes, and heart failure, were most prevalent among black females, followed by black males, white females, and white males. Compared with white patients, black patients were significantly less likely to be angina-free at 6 weeks (female: 48.7% vs. 59.8%; male: 55.0% vs. 65.3%, both p<0.0001) and 12 months (female: 50.6% vs. 61.1%; male: 53.7% vs. 68.9%, both p<0.0001). As shown in the Figure, rates of 1-year unplanned rehospitalization were highest among black females (34.6%), followed by white females (31.3%), black males (30.0%), and white males (25.5%, p<0.0001). In the multivariable model, 6-week angina was the factor most strongly associated with 12-month unplanned rehospitalization (HR 1.40; 95% CI 1.28, 1.54; p<0.0001); this relationship was not modified by race or gender (both p
interaction
>0.05).

Conclusions:
Race and gender differences in post-MI angina frequency exist. Efforts to reduce post-MI rehospitalizations should target improvements in angina treatment.
Abstract 12651: Medication Adherence Mediates the Relationship Between Heart Failure Symptoms and Cardiac Event-Free Survival in Patients With Heart Failure
Authors: Wu Jia-rong , Moser Debra K
Published: April 2024

Background:
Heart failure (HF) symptoms such as dyspnea and ankle swelling are common and may precipitate hospitalization. Poor medication adherence is presumed to be associated with symptom exacerbations and hospitalization, yet how HF symptoms, medication adherence, and hospitalization are related remain unclear.

Objective:
The purpose of this study was to explore the relationships among HF symptoms, medication adherence, and cardiac event-free survival in patients with HF.

Methods:
We enrolled 219 patients with HF (male 65%, age 60±12). Patients’ demographic and clinical data were collected at baseline. Medication adherence was monitored using the Medication Event Monitoring System. HF symptoms were assessed using the Self-Care of Heart Failure Index. Patients were followed for up to 3 1/2 years to collect outcome data. Cardiac events (cardiac rehospitalization and mortality) were obtained by patient/family interview and hospital database review. Linear regression and survival analyses were used for data analyses.

Results:
HF patients who reported dyspnea or ankle swelling were more likely to have poor medication adherence (p = .05). Poor medication adherence was associated with worse cardiac event-free survival (p =.006). In Cox regression, patients with HF symptoms had 2 times greater risk for a cardiac event than patients without HF symptoms (p = .042). HF symptom was not a significant predictor of cardiac event-free survival after entering medication adherence in the model (p = .091), indicating mediation of the relationship between HF symptoms and outcomes by medication adherence (Figure).

Conclusion:
Medication adherence mediated the relationship between HF symptoms and cardiac event-free survival in this sample. It is important to develop interventions to improve medication adherence to reduce HF symptoms and high hospitalization and mortality rates in patients with HF.