bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11192: Correlation of the Predictive Ability of Early Warning Metrics and Mortality for Cardiac Arrest Patients Receiving in-Hospital Cardiopulmonary Resuscitation
Authors: DeVoe Barbara , Roth Anita , Maurer Gregory , Lesser Martin , Pekmezaris Renee , Tamuz Michal , Makaryus Amgad N , Hartman Alan , DiMarzio Paola
Published: April 2024

Introduction:
The Modified Early Warning System (MEWS) is a tool to help monitor patients and improve how quickly a patient experiencing a sudden decline in clinical status receives clinical care.

Hypothesis/Aims:
We assessed the risk factors that may be associated with hospital survival following cardiopulmonary resuscitation (CPR) in response to cardiac arrest (CA). In this study, we also examined the role of Modified Early Warning Score (MEWS) implementation on patients’ survival.

Methods:
Retrospective chart review of all patients who were treated with CPR after experiencing in-hospital CA (n=417) was conducted between January 2007 and December 2013, at a tertiary care hospital in the New York metropolitan area. The investigators determined survival rate for these patients and evaluated their MEWS on admission and during the 4 hours preceding the CA. Multivariable logistic regression was used to adjust for possible confounding factors. Specifically, we analyzed the relationship between MEWS and risk factors such as age, gender, type of electrographic cardiac rhythms, return of spontaneous circulation (ROSC) and MEWS using logistic regression.

Results:
Only 60% of the patient charts reviewed (256/417), indicated a return of spontaneous circulation (ROSC) following CPR. The overall survival rate, defined as survival to hospital discharge, was 21%. Strong predictors for survival were ventricular fibrillation (VF) (p<.0001) and ventricular tachycardia (VT) rhythm (p<.0001). MEWS values at hospital admission (p<.005) and patients of younger age (p<.005) were also significantly associated with survival to hospital discharge. In contrast, gender and MEWS prior to CA were not significantly associated with survival.

Conclusions:
Survival following CPR in response to in-hospital cardiac arrest is significantly associated with VF and VT rhythms and age. Moreover, MEWS at admission was significantly associated with survival, suggesting that higher MEWS scores at admission may be an important predictor of survival. MEWS monitoring may be an effective tool in identifying significant changes in a patient’s vital signs prior CA.
Abstract 11233: Trends in Coronary Revascularization and Ischemic Heart Disease-Related Mortality in Israel
Authors: Blumenfeld Orit , Nhamnih Wasef , Shapira-Daniels Ayelet , Haklai Ziona , Lotan Chaim , Shohat Tamy , Shapira Oz M
Published: April 2024

Introduction:
This study investigated national trends in percutaneous coronary angioplasty (PCI), coronary artery bypass grafting (CABG) and ischemic heart disease (IHD)-related mortality in Israel.

Methods:
Using ICD-9 and 10 codes we linked 5 Israeli national databases: the Centers for Disease Control National PCI and CABG Registries, Ministry of Health Hospitalization Reports, Center of Bureau of Statistics and the Ministry of Interior Mortality Report to assess the annual PCI and CABG volume, procedural mortality, co-morbidities and IHD-related mortality between 2002 and 2014. Time trends were analyzed using linear regression, assuming a Poisson distribution.

Results:
A total of 341,056 revascularization procedures (PCI-298,390, CABG-42,666) were performed during the study period. The volume of PCI increased by 9% from 2002 to 2008 (378.0/100K to 423.2/100K) and then steadily decreased to 378.5/100K in 2014 (p=0.70 for the trend). CABG volume decreased by 58% (109.0/100K to 45.8/100K) from 2002 to 2012 leveling during the last 3 years to 46.3/100K (p<0.0001). The PCI/CABG ratio increased from 3.6 in 2002 to 8.5 in 2012, slightly decreasing to 8.2 by 2014 (P<0.0001). In-hospital procedural mortality remained stable (PCI- 1.2-1.6%, p=0.34, CABG- 3.7-4.4%, p=0.29) despite a significant change in patient characteristics. During the study period, annual IHD-related mortality decreased by 46% (84.6 to 46/100K, p<0.001).

Conclusions:
We observed a dramatic change in coronary revascularization procedures type and volume with a parallel marked decrease in IHD-related mortality in Israel. Improvement in medical treatment, better patient selection related to data derived from large-scale clinical trials and adherence to appropriateness criteria, as well as improved procedural techniques and technology may account for these changes.
Abstract 11330: E/e’ is a Powerful Predictor of Survival After a First-Ever Non-ST Elevation Myocardial Infarction
Authors: Lin Andrew , Kwan Christopher , Sippel Joanne , Guppy-Coles Kristyan , Hammett Christopher , Thomas Liza , Atherton John J , Prasad Sandhir B
Published: April 2024

Introduction:
Significant LV diastolic dysfunction is associated with a poorer prognosis following acute MI. The ratio of early mitral inflow velocity to mitral annular early diastolic velocity (E/e’) is a strong non-invasive correlate of LV filling pressures. Septal E/e’ >15 has been well-validated as a predictor of survival in patients with STEMI, with limited data for patients with NSTEMI.

Aim:
To assess the prognostic significance of E/e’ measured early after a first-ever NSTEMI. We hypothesised that a septal E/e’ >15 would predict poorer survival following NSTEMI.

Methods:
Data analysis on 332 consecutive patients who underwent coronary angiography for a first-ever NSTEMI at a single large tertiary referral centre from January 2013 to December 2014. Transthoracic echocardiography was performed within 24 hours of admission. Outcomes data were obtained from a statewide registry, with the primary endpoint being all-cause mortality.

Results:
At a median follow-up time of 36 months, death occurred in 41 (12%) patients. Septal E/e’ was >15 in 66 patients (20%) and was associated with excess mortality (log-rank statistic 17.7, P<0.0001) (Figure 1). On univariate Cox regression analysis, E/e’ >15, age >80 years, diabetes, chronic kidney disease, LVEF, left atrial volume index >34ml/m
2
and tricuspid regurgitation peak velocity >2.8m/s were associated with the primary endpoint. On multivariate analysis, E/e’ >15 was an independent predictor of all-cause mortality (HR 2.30, 95%CI 1.24-4.33, p=0.028), as was chronic kidney disease (HR 2.73, 95%CI 1.32-5.66, p=0.007) and LVEF (HR 0.96, 95%CI 0.93-0.98, p=0.001). Furthermore, E/e’ >15 showed incremental prognostic value when added to LVEF.

Conclusion:
E/e’ is a powerful, independent predictor of survival following a first-ever NSTEMI. It is superior, in this setting, to most clinical variables and other echocardiographic parameters of diastolic dysfunction, and has additive prognostic value over LVEF.
Abstract 11439: A Role of Esophageal Cancer Related Gene-4 for Atrial Fibrillation
Authors: Yu Hua , Huang Li , Fan Xinrong , Cheng Jun , Li Pengyun , Fan Xuehui , Zeng Xiaorong , Dang Xitong
Published: April 2024

Introduction:
Epidemiological studies have shown that the incidence of atrial fibrillation(AF), the most common type of arrthymia, is more than doubled in cancer patients than that in general population, and
reciprocally
that the incidence of tumor is ten times higher in AF patients than in non-AF patients. However, the molecular link between tumor and AF remain obscure. Esophageal Cancer Related Gene-4 (Ecrg4), a newly-discovered tumor suppressor gene that is highly expressed in atria and conduction systems of heart, has been shown to function as a ‘sentinel’ molecule in tissue homeostasis, meaning that the presence of Ecrg4 calls for no actions, whereas the loss of Ecrg4 upon injury causes the activation of pro-inflammatory cascade and proliferative responses including fibrosis.

Hypothesis:
Since injury-induced loss of Ecrg4 in tumor leads to systemic inflammation and increased fibrosis that are well-known inducing factors to AF, we hypothesize that Ecrg4 in heart plays a critical role in the pathogenesis of AF.

Methods:
The expression of Ecrg4 was evaluated by IHC, IF, and RT-PCR. Canine AF model was established by rapid right atrial pacing at 600 beats/min. for 6 hours.

Results:
The expression of Ecrg4 was higher in atria and conduction systems than that in ventricles of rat heart by IHC, which was confirmed by RT-PCR. In neonatal rat cardiomyocytes, the expression of Ecrg4, localized in perinucler region and in the ER, is higher in atria than in ventricles. Knock-down Ecrg4 expression by siRNA in atrial cardiomyocytes significantly shortened the duration of action potential. Moreover, in a canine AF model, the expression of Ecrg4 in both Sinus node and left atria was significantly down-regulated compared to that in control animals.

Conclusions:
Expression of Ecrg4 is high in atria and heart conduction systems and down-regulated in AF, suggesting that Ecrg4 may play a critical role in the pathogenesis of AF.
Abstract 11443: Higher Leptin Levels are Associated With Reduced Left Ventricular Mass and Left Ventricular Diastolic Stiffness in African American Women: Insights From the Genetic Epidemiology Network of Arteriopathy (GENOA) Study
Authors: Kamimura Daisuke , Suzuki Takeki , Wang Wanmei , Deshazo Matthew D , Hall John E , Winniford Michael D , Mosley Thomas H , Butler Kenneth R , Hall Michael E
Published: April 2024

Background:
Leptin has been associated with left ventricular (LV) hypertrophy and heart failure in some epidemiologic studies while other studies have demonstrated a beneficial effect on cardiac remodeling and function. We hypothesized that leptin may play a role in protecting the heart from developing LV hypertrophy and stiffening.

Methods and Results:
We evaluated 1172 African Americans with preserved LV ejection fraction (EF >50%) from the Genetic Epidemiology Network of Arteriopathy (GENOA) Study (mean age 62.9 years, 72% women). LV diastolic stiffness was assessed by echocardiography using the diastolic wall strain (DWS) indicator. Associations between leptin levels and indices of LV structure and function were evaluated using generalized estimating equations (GEE) approach with Gaussian distribution accounting for clustering in siblings. All models were adjusted for possible confounders including age, body mass index, systolic blood pressure, blood pressure lowering medication, coronary heart disease, current smoking status and estimated glomerular filtration rate and stratified by sex because leptin levels were three times higher in women than men (p <0.001). After adjustment, higher leptin levels were associated with lower LV mass and less LV diastolic stiffness (p <0.05, for both) in women, while there were no statistically significant associations between leptin levels and LV structure and function in men. In women, there were interactions between leptin levels and body mass index quartiles on LV mass and LV diastolic stiffness (p <0.05, for both). Higher leptin levels were associated with lower LV mass and LV diastolic stiffness more in obese rather than in lean women (Figure).

Conclusions:
Higher leptin levels were associated with lower LV mass and LV diastolic stiffness in obese African American women. Leptin may play an important role in protecting the heart from developing precursors to heart failure in obese African American women.
Abstract 11579: Physical Activity versus Body Mass Index and Prevalence of Peripheral Arterial Disease
Authors: Dwivedi Aeshita , Rockman Caron , Guo Yu , Stein Rich , Adelman Mark , Berger Jeffrey S
Published: April 2024

Introduction:
Physical activity and body mass index (BMI) are independently associated with peripheral arterial disease (PAD). However, their relative significance and combined association with PAD remain unclear.

Hypothesis:
We hypothesize that physical activity is associated with a lower odds of PAD across the BMI spectrum and that physical activity attenuates the prevalence of PAD in obese patients.

Methods:
We studied 3,250,350 U.S. adults who self-referred for PAD screening from 2003-2008 (Life Line Screening Inc., Independence, Ohio). Subjects completed a medical/lifestyle questionnaire. They were categorized into physically active or physically inactive based on their response in the questionnaire to whether they engaged in any type of vigorous leisure time exercise on a regular basis. All subjects were evaluated for PAD by ankle brachial index, with <0.9 considered abnormal. We divided participants into standardized BMI categories: underweight (< 18.5), normal weight (18.5-24.9), overweight (25-29.9), obese class I (30-34.9), class II (35-39.9), and class III (> 40). Multivariable logistic regression was used to estimate the odds of PAD among the BMI categories, based on physical activity.

Results:
Overall, mean age was 63.1 ± 10.5 years, 65.5% were female, and mean BMI was 27.7 ± 5.8 kg/m
2
. 41.5% were physically inactive. Average BMI was higher in the physically inactive versus physically active group (28.9 ± 6.3 vs. 27.0 ± 5.3, P<0.0001). Prevalence of PAD initially decreased and then increased with BMI and was attenuated with physical activity. Following multivariable adjustment, physical activity was independently associated with lower odds of PAD across the BMI spectrum (Table).

Conclusion:
Physical activity is associated with lower odds of PAD in underweight, normal weight, overweight and obese individuals. The higher prevalence of PAD with increasing BMI is attenuated with physical activity.
Abstract 11583: Liver Stiffness Assessed by Fib4 Index Predicts Mortality in Heart Failure Patients
Authors: Sato Yu , Yoshihisa Akiomi , Watanabe Shunsuke , Yokokawa Tetsuro , Miura Shunsuke , Sato Takamasa , Suzuki Satoshi , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Kunii Hiroyuki , Saitoh Shu-ichi , Takeishi Yasuchika
Published: April 2024

Background:
Liver dysfunction due to heart failure (HF) is often referred as cardiac or congestive hepatopathy. FIB4 index (age [years] х aspartate aminotransferase [IU/L] / platelet count [10
-9
/L] х radical alanine aminotransferase [IU/L]) is expected to be useful for evaluating liver fibrosis in patients with nonalcoholic fatty liver disease. It has been recently reported that liver stiffness assessed by transient elastography predicts adverse prognosis in HF patients. We aimed to investigate the impact of FIB4 index on prognosis of HF and compare the underlying cardiac function.

Methods and Results:
We analyzed 1268 HF patients who admitted to our hospital. Out of these patients, patients with hepatitis and chronic liver disease were excluded, and 1058 patients were finally analyzed. These patients were divided into 3 groups based on the FIB4 index: 1st, 2nd and 3rd tertile (n=353, each). In the follow-up period (mean 1047 days), 246 deaths (122 cardiac deaths and 124 non-cardiac deaths) occurred. In the Kaplan-Meier analysis, all-cause mortality progressively increased from 1
st
to 2
nd
and 3
rd
groups (12.2, 21.0 and 36.6%, P <0.001). In the Cox proportional hazard analysis, FIB4 index was an independent predictor of all-cause mortality in HF patients (hazard ratio 1.79, 95% confidence interval 1.29-2.49, P<0.001). In addition, we compared echocardiographic findings among the three groups. Left ventricular ejection fraction and right ventricular fractional area change did not differ among three groups. In contrast, the 3rd tertile, compared to 2nd and 1st tertiles, had higher levels of left atrial volume (92.5 vs. 82.8, and 74.9 ml, P < 0.01), mitral valve E/e’ (16.6 vs. 15.3, and 13.8, P < 0.01), inferior vena cava diameter (16.2 vs. 14.5, and 14.4 mm, P < 0.01) and right atrial area (20.9 vs. 17.4, and 17.6 cm
2
, P < 0.01).

Conclusion:
FIB4 index, a marker of liver stiffness, is associated with larger right and left heart volume overload, and higher mortality in HF.
Abstract 11595: Predicting Appropriate Shocks In Patients With Heart Failure: Patient Level Meta-analysis From SCD-HeFT and Madit II
Authors: Zeitler Emily P , Al-Khatib Sana M , Friedman Daniel J , Han Joo Yoon , Bardy Gust H , Bigger J. T , Buxton Alfred E , Moss Arthur J , Lee Kerry L , Steinman Richard , Dorian Paul , Hallstrom Alfred , Cappato Riccardo , Kadish Alan H , Kudenchuk Peter J , Mark Daniel B , Inoue Lurdes Y , Sanders Gillian D
Published: April 2024

Background:
Some patients implanted with a primary prevention implantable cardioverter defibrillator (ICD) due to heart failure receive an appropriate shock, but no precise tools exist to predict this outcome.

Methods:
Using patient level data from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), we identified patients with any appropriate ICD shock. A variety of clinical and demographic variables were included in a logistic regression model to predict appropriate ICD shocks (Table).

Results:
There were 1,463 patients randomized to ICD from the two included trials; 285 (19%) had ≥1 appropriate shock over a median follow up of 2.59 years. Compared with patients with no appropriate shocks, patients who received any appropriate ICD shock tended to have NYHA class II or III heart failure symptoms, beta blocker therapy, lower LVEF, wider QRS duration, and a single versus dual chamber ICD (79% of all patients had a single chamber ICD). Other comorbidities were similar between groups. Significant independent predictors of appropriate ICD shocks included NYHA class (NYHA II vs I: OR 1.65, 95% CI 1.07-2.55; NYHA III vs I: OR 1.74, 95% CI 1.10-2.76), LVEF based on one unit change (higher vs lower LVEF: OR 0.96, 95% CI 0.94-0.98), beta blocker therapy (presence vs absence: OR 0.96, 95% CI 0.94-0.98), and single chamber ICD (OR 1.67, 95% CI 1.13-2.45).

Conclusion:
In this meta-analysis of patient level data from MADIT-II and SCD-HeFT, appropriate ICD shocks were significantly predicted by NYHA class, LVEF, beta blocker therapy, and single chamber ICD. There is a compelling need for a large, prospective study to better define the risk of appropriate ICD shocks in patients meeting criteria for a primary prevention ICD. Until such time, stratification of patients by these factors may better define risk for potentially mortal rhythm events that might be prevented by a primary prevention ICD.
Abstract 11607: Effects of Delayed Treatment With Inhaled Hydrogen on Oxidative Stress and Inflammatory Cytokines After Resuscitation in a Porcine Model of Cardiac Arrest
Authors: Yang Zhengfei , Yu Tao , Wen Cai , Zhai Xiaozhu , Peberdy Mary Ann , Ornato Joseph P , Tang Wanchun
Published: April 2024

Introduction:
Immediate treatment with inhaled hydrogen (H
2
) has been demonstrated to attenuate oxidative stress conditions and inflammatory cytokines in serum after resuscitation from cardiac arrest. However, early applying inhaled H
2
is not practical especially in out of hospital cardiac arrest because of the safety issue. In the present study, we investigated the effects of delayed treatment with H
2
on oxidative stress and inflammatory cytokines in a porcine model of cardiac arrest (CA).

Hypothesis:
Delayed inhalation of H
2
reduces proinflammatory cytokines but without effect on oxidative stress after resuscitation in a CA porcine model.

Methods:
Twenty male domestic pigs weighing 39±2 kg were studied. Ventricular fibrillation (VF) was induced electrically and CPR was initiated after 10 min of untreated VF. Animals were randomized into two groups immediately after successfully resuscitation: delayed inhalation of H
2
(DH group) or continuous inhalation of room air (C group). DH group animals were ventilated with 2% H
2
/21% oxygen from post-resuscitation 120 min (PR120) until PR240 min. Serum levels of oxidative product (8-iso-PGF
2α
) and proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and high-mobility group box protein 1 [HMGB1]) were measured by ELISA at baseline (BL), PR30, PR180 and PR360.

Results:
Serum levels of 8-iso-PGF
2α
in all the animals were significantly

increased at PR30 then decreased to the levels of BL after PR180. The levels of TNF-α, IL-6 and HMGB1 in serum of all animals were elevated after PR180. Although no significant differences in the levels of 8-iso-PGF
2α
were observed between both groups, the levels of TNF-α, IL-6 and HMGB1 were significantly lower in DH group animals when compared with those in C group (Figure).

Conclusions:
Delayed treatment with H2 attenuates proinflammatory cytokines but without effect on oxidative stress conditions after resuscitation.
Abstract 11635: Non-Alcoholic Fatty Liver Disease and Subclinical Atherosclerosis in Mexican Americans
Authors: Gill Clarence D , Vatcheva Kristina P , Pan Jen-Jung , Smulevitz Beverly , Fallon Michael B , McPherson David D , McCormick Joseph B , Fisher-Hoch Susan P , Laing Susan T
Published: April 2024

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome, whose criteria are risk factors for atherosclerotic CVD. We aimed to evaluate the prevalence of NAFLD, its association with subclinical atherosclerosis, and factors that may account for this association in Mexican Americans.

Methods:
In a population based cross-sectional sample (n=164) drawn from the Cameron County Hispanic Cohort in Texas, carotid intima media thickness (cIMT), an indicator of subclinical atherosclerosis, was measured by ultrasound. Abnormal carotid study was defined as mean cIMT >75
th
percentile for age and gender and/or plaque presence. NAFLD was defined as steatosis by ultrasound in absence of other causes of liver disease. Multivariable weighted regression analyses were performed to evaluate associations between NAFLD and cIMT.

Results:
Mean age was 50.3±1.8 years with 60% females. Mean BMI was 30.1 ± 0.4 kg/m2 with 61% meeting criteria for the metabolic syndrome. There was a very high prevalence of NAFLD (49%) among Mexican Americans. Subjects with NAFLD had greater BMI, abdominal obesity, fasting glucose levels, dyslipidemia, and tended to have diabetes or metabolic syndrome. A third of subjects with NAFLD also had evidence of subclinical atherosclerosis (33%). After adjusting for covariates, there was an independent association between NAFLD and increased cIMT, but only in younger subjects <55 years (p=0.02). Subjects who had both abnormal liver and carotid ultrasound studies tended to be obese, diabetic, and have the metabolic syndrome.

Conclusion:
There is a very high prevalence of NAFLD in this Mexican American cohort, with an independent association between NAFLD and subclinical atherosclerosis among younger subjects. Clustering of diabetes, obesity, and metabolic syndrome in this health disparity cohort, with increased risk of both liver disease and atherosclerosis, warrants attention and aggressive intervention.
Abstract 11738: Migraine With Aura, an Undescribed Complication of Catheter Ablation of Atrial Fibrillation
Authors: Kuehlkamp Volker , Gass Matthias , Stanciu Bogdan , Eigenberger Bernd
Published: April 2024

Catheter ablation (CAbl), requiring transseptal puncture, has emerged to a standard procedure in patients (Pts) with symptomatic atrial fibrillation (AF). Frequently a small right to left shunt can be observed with Valsalva maneuvers after the procedure. A recent meta-analysis suggests that migraineurs with aura are more than 4x more likely to have a PFO than the general population. We describe a hitherto unrecognized phenomenon following CAbl of AF (439 consecutive Pts, 1/2015 to 3/2016, mean age 63±11 years, 66.5% male gender). CAbl was performed using radio frequency current (RF, n=260, Navistar Thermocool
TM
, settings 20watt to 40watt, 43°C) or cryo-energy (CRYO, n=179 paroxysmal AF only, Arctic Front Advance
TM
, <-40°C to ≥-60°C). CAbl was performed during uninterrupted oral anticoagulation (OAC) with a vitamin K antagonists (n=128, INR >2) or with direct OAC (Dabigatran n=89, Rivaroxaban n=148, Apixaban n=73, Edoxaban n=1). After CAbl Pts underwent continuous ECG-monitoring, a neurologic evaluation followed the procedure immediately and was repeated after 24h. Pts were encouraged to report any complaints. Eight Pts (1.8%) had short lasting neurologic complaints and received, as part of the work-up, cerebral magnetic resonance imaging (MRI). Two Pts with transient neurologic deficits (vertigo n=1, Phenprocoumon, INR 2.4, speech disorders n=1, Rivaroxaban 20mg) had new small ischemic cerebral lesions. All 6 Pts (Dabigatran n=3, Rivaroxaban n=2, Phenprocoumon n=1, INR 2,1, RF n=2, Cryo n=4) with negative MRI had visual disturbances, followed by headache, as typically reported by migraineurs. One patient had a history of migraine with aura, five Pts never before had similar complaints. Pts with visual disturbances and headache continued to have similar complaints during the following 2 weeks. Follow-up of both patients with new ischemic lesions was inconspicuous.

Conclusion:
Recurrent migraine with visual disturbances occurred after CAbl of AF in about 1.5% of Pts with uninterrupted OAC who never had migraine before. It seems likely that the mechanism of visual disturbances followed by headache after CAbl of AF resembles the mechanism of migraine in patients with PFO. It is unknown whether migraine may become a chronic condition after CAbl of AF.
Abstract 11807: Phenotyping Family History of Coronary Heart Disease to Inform Risk Assessment for Cardiovascular Events in MESA
Authors: Patel Jaideep , Al Rifai Mahmoud , Patel Pradeep , Scheuner Maren , Shea Steven J , Blumenthal Roger S , Nasir Khurram , Blaha Michael J , McEvoy John W
Published: April 2024

Introduction:
The relationships between various family history (FH) of coronary heart disease (CHD) phenotypes and cardiovascular disease (CVD) events have not been fully explored.

Hypothesis:
The association between FH and CVD will differ by, 1) FH at any age vs. premature FH in a parent, sibling, or child, and 2) familial risk score strata (weak, moderate, or strong; see
Table
for details).

Methods:
We ascertained CVD events (CHD, angina, stroke, peripheral arterial disease [PAD], and heart failure [HF]) over a median of 10.1 years. Multivariable Cox models examined the association of FH with CVD events (individual and composite). The C-statistic assessed the prognostic impact of FH for predicting CVD when added to traditional RFs.

Results:
Of 6192 adults [mean (±SD) age 62±10 years, 48% men, 40% white] with information on FH, 36% reported any FH. Those with strong familial risk (n=1240) were more likely to be diabetic, overweight, smoke, or take medication for hypertension and dyslipidemia. Overall, 741 CVD events occurred. Compared to no FH, any FH was associated with incident CHD, angina, and composite CVD in adjusted models [hazard ratio (95% CI)]: 1.4 (1.1-1.8), 1.6 (1.2-2.1), and 1.3 (1.1-1.5), respectively]. Nearly identical results were obtained for premature FH (
Table
). Compared to weak familial risk, strong risk was also associated with CHD, angina and CVD. However, there was no association between FH of any type and stroke, PAD, or HF. FH status (any or premature) and familial risk score improved discrimination of CVD (p

=0.0005, p=0.005, and p=0.001, respectively). Familial risk score provided marginal discrimination over and above premature FH status (C statistic from 0.742 to 0.744, p=0.051).

Conclusion:
The association between FH and CVD risk differs depending on the number of affected family members, suggesting the value of detailed FH information to refine risk assessment. The predictive value of FH of CHD for non-coronary events is limited.
Abstract 11819: Impact of Dynamic Changes of Elevated Bilirubin on Survival in Patients on Veno-Arterial Extracorporeal Life Support for Acute Circulatory Failure
Authors: Freundt Miriam I , Lunz Dirk , Philipp Alois , Rupprecht Leopold , Hirt Stephan , Flitter David , Schmid Christof , Haneya Assad
Published: April 2024

Introduction:
Veno- arterial extracorporeal life support (ECLS) is an established method to stabilize acute circulatory failure by providing immediate gas exchange and peripheral tissue perfusion. Parameters and data on when to ideally wean circulatory support are limited.

Hypothesis:
Bilirubin levels may serve as indicator for readiness to wean ECLS. The purpose of this study was to evaluate the impact of dynamic changes of elevated bilirubin levels on survival in a large patient population on ECLS.

Methods:
We reviewed 502 consecutive cases of ECLS from 2007 to 2015. Bilirubin levels were recorded before implantation and then daily until six days after explantation. Bilirubin levels were statistically correlated with the primary outcome parameter 30-day survival and the secondary outcome parameters successful weaning and non-survival on ECLS. A multivariate regression analysis was performed to identify independent risk factors. Boxplots were generated to visualize dynamic changes in bilirubin levels.

Results:
Reason for ECLS was cardiac arrest with ongoing resuscitation in 230 (45.8%), low cardiac output in 174 (34.7%) and inability to wean off cardiopulmonary bypass in 98 (19.5%) patients. 307 (61.2%) patients were weaned off ECLS, however, only 206 (41.0%) ultimately survived 30 days. Mean duration of ECLS was 3 (2-6) days, and survivors received significantly longer ECLS (5 vs 3 days,
p < 0.001
). Survivors had significantly lower bilirubin levels initially and on day 1 (
p = 0.003
and
p = 0.013
). Bilirubin started to rise notably from day 2 in all patients. In survivors bilirubin levels had trended down on the day of ECLS explantation and stayed at an acceptable level. However, in weaned patients and nonsurvivors bilirubin levels remained above baseline or even continued to rise during the recorded period.

Conclusion:
Down trending bilirubin levels on ECLS indicate improved chances of survival and may warrant weaning off support in hemodynamically stable patients.
Abstract 11846: Cardiac Mitofusin1 Level Predicts the Response to the Treatment of Heart Failure Among Patients With Idiopathic Dilated Cardiomyopathy
Authors: Watanabe Tohru , Shimizu Ippei , Jiao Shuang , Kashimura Takeshi , Yoshida Yohko , Hanawa Haruo , Ozaki Kazuyuki , Minamino Tohru
Published: April 2024

Medications targeting cardiac remodeling have become first-line therapy for heart failure. Some patients do not respond to the established treatment and described as non-responders. The prognosis of non-responders is poor and it is our urgent task to understand the underlying mechanism and find new therapeutic targets for this critical condition. In this context, it is essential to find biological markers of non-responding patients. Here we show that mitochondrial size and number in cardiomyocytes is significantly reduced, and this condition associates with a low mitochondrial fusion marker in the cardiac tissue of non-responders with idiopathic dilated cardiomyopathy (IDCM). We examined IDCM patients who underwent endomyocardial biopsy of intraventricular septum. Patients were classified as non-responders when their left-ventricular (LV) ejection fraction and LV end-diastolic dimension did not show more than 10% improvement by the follow-up echocardiogram performed in 7-15months after the biopsy. No differences in the medications and age were observed between the groups. Transmission electron microscopy showed a significant reduction in both the size and number of mitochondria in the cardiomyocytes of non-responders (n=5) compared to responders (n=6) (0.2077±0.025 vs 0.2785±0.022μm
2
; p<0.05, 250±32 vs 344±48 mitochondria/field; p<0.01). Quantitative PCR and immunofluorescence studies showed a significant reduction in mitofusin1, a critical regulator of mitochondrial fusion, but molecules involved in mitofission (
DNM1L
and
FIS1
) and mitophagy (
BNIP3
and
MAP1LC3A
) did not show difference between the groups. Studies with neonatal rat ventricular myocytes suggested that beta-1 adrenergic receptor mediated signaling pathway is critically involved in the regulation of
Mfn1
, and the suppression of
Mfn1
led to the significant reduction in mitochondrial respiration. We also found that cardiac
ADRB1
is markedly reduced in non-responders. These results indicate that cardiac mitofusin1 would become a biomarker for non-responders in IDCM patients. In addition, our results suggest that therapies targeting mitochondrial dynamics and homeostasis would become next generation therapy for heart failure patients.
Abstract 11868: Intracardiac Pressures Measured Using an Implantable Hemodynamic Monitor: Relationship to Mortality in Patients With Chronic Heart Failure
Authors: El Hajj Stephanie , Bennett Tom D , Zile Michael R , Kueffer Fred J , Baicu Catalin F , Abraham William T , Bourge Robert C , Stevenson Lynne
Published: April 2024

Introduction:
The use of implantable hemodynamic monitor (IHM)-derived pressure to facilitate management of chronic heart failure (CHF) has been shown to decrease ventricular filling pressures and reduce heart failure hospitalizations. However, whether IHM-derived pressures predict mortality rate is unknown.

Hypothesis:
Determine whether IHM-derived baseline estimated pulmonary artery diastolic pressure (ePAD) and change from baseline ePAD were independent predictors of all-cause mortality in patients with CHF.

Methods:
A retrospective analysis used data from three studies in CHF patients with an IHM (n=790). Baseline ePAD, mean of daily median ePAD from 0-14 days after IHM implantation, was related to mortality using a multivariable model including baseline and demographic data. Change in ePAD defined from baseline to 6 month and from baseline to 14 days prior to death or exit from study were related to mortality. Area under the pressure vs time curve (AUC) during 180 days prior to death or exit from study was related to mortality.

Results:
Baseline ePAD, independent of other covariates, was a significant predictor of mortality (Chi-square=36.7, HR=1.067, 95% CI=1.047, 1.089, p<0.0001)
(Fig. A).
Change in ePAD was a predictor of mortality. There was a significant relationship between change in ePAD from baseline to 6 months and mortality (HR=1.074, 95% CI=1.048, 1.100, p=0008). Change in ePAD = 3, 4, or 5 mmHg from baseline to 6 months was associated with a change in mortality risk of 23.8%, 32.9%, or 42.8% respectively
(Fig. B).
Change in ePAD from baseline to 14 days prior to death or exit from study was higher in patients that died 3.0±8 vs 1.7±10 mmHg, p=0.003). AUC in the 180 days prior to death or exit from study was higher in the patients that died (185±668 vs 17±482 mmHg.days, p=0.006).

Conclusions:
Implantable hemodynamic monitor -derived baseline ePAD and change from baseline ePAD were independent predictors of mortality in CHF patients.
Abstract 11871: Morphologic Features Predict Late Adverse Events in Uncomplicated Stanford Type-B Aortic Dissection
Authors: Sailer Anna M , Nelemans Patty , van Kuijk Sander M , Chin Anne S , Kino Aya , Chiu Peter , Fischbein Michael P , Dake Michael D , Miller D C , Schurink Geert W , Fleischmann Dominik
Published: April 2024

Introduction:
Medical treatment of uncomplicated Stanford type-B aortic dissection (AD) is associated with a high rate of late adverse events (AE). Endografting may prevent late complications, however, initial trials failed to demonstrate a survival benefit in the first two years. We hypothesize that morphologic features at the initial hospitalization are associated with AE and could aid in the risk stratification of patients with AD.

Methods:
Eighty-three patients with acute uncomplicated type-B AD were retrospectively identified at two aortic centers in the US and EU. Multiple clinical and morphologic features - including true vs. false lumen blood supply - were identified on high-quality CT scans and followed. Multivariable Cox proportional hazards regression was used to evaluate the associations between candidate predictors and AE - defined as rapid growth, aneurysm formation (≥6cm), organ ischemia, and fatal or non-fatal aortic rupture, and develop an internally validated risk score.

Results:
AE were observed in 33 patients over a median 850 (IQR 247-1824) days follow up. Five significant predictors were identified in the multivariable model: Connective tissue disease (HR 2.94, 95% CI: 1.29 - 6.72, p= 0.01), circumferential extent of false lumen in angular degrees (HR 1.03, 95% CI: 1.01 - 1.04, p= 0.003), maximum aortic diameter in mm (HR 1.10, 95% CI: 1.02 - 1.18, p= 0.015), false lumen outflow in mL/min (HR 0.999, 95% CI: 0.998 - 1.000, p= 0.055), and number of intercostal arteries (HR 0.89, 95% CI: 0.80 - 0.98), p= 0.024). A model combining these five factors was constructed to calculate patient specific risk scores allowing stratification into high, intermediate, and low risk terciles. The model showed good discriminatory ability with an optimism-corrected c-statistic of 70.1%.

Conclusion:
Morphologic features predict late AE in uncomplicated type-B AD. If externally validated this may identify high-risk patients who benefit from early endografting.
Abstract 11877: Beta-blocker Dose Stratifies Both Mortality Risk and Circulating Procollagen Levels In African-Americans With Heart Failure
Authors: Duarte Julio D , Arwood Meghan J , Liko Ina , Mansour Ibrahim , Kansal Mayank , Stamos Thomas , Cavallari Larisa H , Desai Ankit A
Published: April 2024

Introduction:
While African Americans (AAs) have the highest prevalence of heart failure (HF) and HF mortality, insufficient data exists regarding the impact of HF medication on mortality in AAs. This study aimed to identify medication use practices associated with survival in a predominantly AA HF population.

Methods:
HF patients were prospectively recruited from, and followed within, the University of Illinois Health System from 11/2001 to 11/2015, when vital status was determined. Data were extracted from electronic health records and Social Security Death Index. Beta-blocker (BB), ACE-I, and ARB doses were categorized as high, medium, or low based on published HF trials. Associations between dose and all-cause mortality were assessed using a Cox proportional hazard model, adjusting for enrollment age, sex, race, ischemic or non-ischemic etiology, NYHA functional class, and concomitant HF medication use. Using linear regression (adjusted for the same covariates), doses were also compared with plasma procollagen N-terminal peptide type III (PIIINP) levels, a previously shown marker for cardiac fibrosis.

Results:
In total, 352 patients (75% AA, 50% female, 63% HFrEF: LVEF < 45%) consented to participate, with 84 dying by the end of data recording. Of those, 95% used BBs, 90% ACE-I/ARBs, and 19% ARAs. ACE-I/ARB dose was not associated with mortality (HR: 0.86, 95% CI: 0.62-1.17, P = 0.33). In contrast, increased BB dose was associated with reduced risk of death (HR: 0.64, 95% CI: 0.47-0.86, P = 0.003; Figure 1). This effect remained consistent when stratified by HFrEF or HFpEF. Higher BB (but not ACE/ARB) dose was also associated with lower circulating levels of PIIINP (N = 149 patients, P = 0.05), which still trended after further adjustment for BP and HR.

Conclusions:
These findings suggest that aggressive titration of BB dose, unlike ACE-I/ARB dose, may confer a mortality benefit in AA patients with HFrEF or HFpEF which may be mediated through decreased cardiac fibrosis.
Abstract 11894: Deficiencies of Water-soluble Vitamin Intake Predict Shorter Event-free Survival in Patients With Heart Failure
Authors: Lee Kyoung Suk , Park Jae-Hyeong , Moser Debra K , Dunbar Sandra B , Pressler Susan J , Lennie Terry A
Published: April 2024

Introduction:
Water-soluble vitamins play an important role in producing adenosine triphosphate and decreasing oxidative stress. Because water-soluble vitamins are not stored, inadequate dietary intake leads to water-soluble vitamin deficiencies, which may be associated with adverse health effects. Patients with heart failure (HF) are at risk for water-soluble vitamin deficiencies even if their water-soluble vitamin intakes meet dietary recommended intake as diuretics are routinely prescribed to this population. However, there are few studies, which have measured the relationship between deficiencies of water-soluble vitamin intake and outcomes in HF.

Purpose:
To determine whether deficiencies of water-soluble vitamin intake predicted event-free survival in patients with HF

Methods:
Using a prospective, observational study design, patients with HF were recruited from HF clinics. A total of 216 patients with HF (61years; 34.3% female; 53.7% NYHA I/II; 71.8% LVEF ≤ 40%) were included in this analysis. Four-day food diary analyzed by Nutrition Data System-Research software was used to determine water-soluble vitamin dietary deficiencies (i.e., 8 B vitamins and vitamin C). Event-free survival was defined as a composite endpoint of all-cause death, cardiac hospitalization, or emergency department visit for cardiac reasons. Monthly calls to patient or family and medical record reviews were used to determine event-free survival for 12 months.

Results:
The average number of water-soluble vitamin deficiencies was 1 (SD 1.24) with the range of 0 -7. There were 63 events during the median follow-up of 356 days. Multivariable Cox regression showed that each unit increase in the number of water-soluble vitamin deficiencies was associated with a 1.3-fold increase in risk for an event (95% CI 1.02-1.66), after adjusting for age, gender, NYHA functional class, reduced LV function (i.e., LVEF≤ 40%), N-terminal pro B-type natriuretic peptide, total comorbidities, and use of diuretics (yes/no).

Conclusions:
Deficiencies of water-soluble vitamin intake were associated with a shorter event-free survival in patients with HF. This result suggests a potential benefit to correcting water-soluble vitamin deficiencies in this population.
Abstract 11896: Percutaneous Left Atrial Appendage Closure is Reasonable Option for the Treatment of Patients With Atrial Fibrillation at High Risk for Cerebrovascular Events
Authors: Teiger Emmanuel , Thambo Jean-Benoit , Defaye Pascal , Hermida Jean-Sylvain , Gras Daniel , Klug Didier , Juliard Jean-Michel , Pasquie Jean-Luc , Rioufol Gilles , Lepillier Antoine , Elbaz Meyer , Horvilleur Jerome , Brenot Philippe , Babuty Dominique , Le Corvoisier Philippe ,   on behalf of FLAAC investigators
Published: April 2024

Introduction:
Percutaneous left atrial appendage (LAA) closure is an emerging alternative intervention for anticoagulant treatment in patients with atrial fibrillation and high risk of cerebrovascular events. Only few data are available on the prognosis of patients treated with this new interventional strategy.

Hypothesis:
The aim of the multicenter prospective French national LAA Closure registry (FLAAC) was to report the results of this procedure in daily practice in France.

Methods:
Patients referred from October 2013 to September 2015 to 36 French centers for percutaneous LAA closure were prospectively included in this observational registry. We report here the results of the 436 first patients with one year follow-up.

Results:
The mean (±SEM) age of the study population was 75.5 ± 0.4 years and 62.2 percent were men. Their average CHA
2
DS
2
-VASc and HAS-BLED scores were 4.5 ± 0.1 and 3.1 ± 0.1, respectively. Fifty-height percent of patients were treated with an Amplatzer
™
LAA Occluder and 42% with a Watchman
™
device. LAA closure was successful in 98.4% of patients (including 9 patients requiring two procedures with a different device). The mean follow-up period was 12.7 ± 0.2 months after implantation of the device and only one patient was lost to follow-up. In patients with successful device implantation, ischemic stroke and cerebral hemorrhage rates were 0.22 and 0.11% per month during the follow-up period. The survival rate was 91.1% (38 deaths/429), with 7 (1.6 %) deaths related or possibly related to the device or to the procedure. Other causes of death were cerebral ischemic and hemorrhagic events (0.2% and 0.7%, respectively), major non-cerebral hemorrhagic events (0.7%), known or suspected cardiovascular diseases (2.3 %) and other preexisting non-cardiovascular comorbidities (3.3%).

Conclusion:
In conclusion, this national prospective registry shows that LAA closure is mainly used in patients with very high risk of cerebrovascular events. In this population, this procedure appears to be a reasonable option in daily practice. The high percentage of deaths related to comorbidities suggests that patient global clinical status should also be evaluated to assess patient eligibility before the procedure.
Abstract 11938: Risk Factors for Subarachnoid Hemorrhage
Authors: Sundstrom Johan , Svennblad Bodil , Söderholm Martin , Söderberg Stefan , Eriksson Maria , Malfert Mauricio , Heller Susanne , Engström Gunnar , Wiberg Bernice ,   on behalf of the Swedish Cohort Consortium
Published: April 2024

Introduction:
Subarachnoid hemorrhage (SAH) is a devastating disease, with a high mortality rate and significant disability among survivors. Its causes are poorly understood.

Hypothesis:
We aimed to investigate risk factors for SAH using an adequately powered novel nationwide cohort consortium with uniform collection of clinical outcomes.

Methods:
We obtained individual participant data of 949,683 persons (330,334 women) who were between 25 and 90 years old and had no history of SAH at baseline, from 21 population-based cohorts collected during more than 50 years and geographically covering entire Sweden. Outcomes were obtained from the Swedish Hospital Discharge and Causes of Death Registries.

Results:
During 13,704,959 person-years of follow up, 2,659 first-ever fatal or non-fatal SAH instances were observed. In Poisson regression models with random effects for the cohort level, referencing the population distribution in Sweden year 2010, we observed an age-standardized incidence rate of 9.0 (95% confidence interval 7.4-10.6)/100,000 person-years in men and 13.8 (11.4-16.2)/100,000 person-years in women; rate ratio (RR) 1.45 (1.32 to 1.61) for women vs. men. The incidence rate increased exponentially with higher age, with a plateau of similar risk between ages 55 and 75. The RR was 8.28 (4.39 to 15.63) for age-group 85-89 vs. 25-29 years. Lower education level was associated with higher risk, RR 1.56 (1.27 to 1.96) for primary education vs. post-secondary education. Smoking was associated with a markedly increased risk, with an interaction between smoking and sex. Smoking conferred a RR of 1.66 (1.49 to 1.85) in men, and 2.63 (2.27 to 3.05) in women (p<0.01 for interaction). Hypertension was associated with a RR of 1.33 (1.22 to 1.45) for SAH. Several other risk factors were investigated.

Conclusions:
In this large population-based study, a nearly 50% higher risk of SAH was observed in women than in men. Besides higher age, smoking was the most powerful risk factor for SAH, with a markedly stronger effect in women than in men. Lower education was also linked to higher risk.