bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10325: A Typology of Self-Care Among Older Workers With Coronary Heart Disease (CHD)
Authors: Dickson Victoria , Warren Nicholas , Jun Jin , D'Eramo Melkus Gail
Published: April 2024

America’s workforce is aging. As a result, health problems associated with aging, like CHD present new health challenges. Self-care is essential to cardiovascular health, but how self-care behaviors vary among older workers with CHD has not been explored.

Objective:
To identify self-care types of aging workers with CHD and identify the characteristics and work-related determinants of self-care types.

Methods:
In a sample of 125 older workers with CHD, 2-step cluster analysis was used to identify patterns of similarity among self-care behaviors on the maintenance scale of the Self-Care of Heart Disease Index and the General Adherence Scale.

Results:
Self-care in the sample clustered best into three categories: experts, novices and inconsistent. Experts (n=34, 36.4%), reported the highest levels of self-care (89.2±6.3) and high self-efficacy (75.9±19.1). Novices (n=45, 45.5%), reported adequate self-care (74.3±8.2) but inadequate self-efficacy (59.5±20.2). Those labeled as inconsistent (n=18, 18.2%), had inadequate self-care (57.2±13.2) and marginal self-efficacy (64.6±18.7). Although all types reported medication adherence, experts were more likely to monitor symptoms, keep doctors’ appointments and engage in healthy behaviors (e.g, exercising,limiting alcohol). Those inconsistent in self-care were more likely to be overweight, not follow diet, limit alcohol or avoid cigarettes. Experts and novices were more likely to be in professional or managerial positions that afforded them increased job control. The model predicting self-care type was significant (
X
2
17.622, p=.001, Nagelkerke pseudo-

R
2

=.22); self-efficacy and length of time with CHD were the only significant factors. Higher level of self-efficacy was associated with an increase in odds that subjects would be typed as expert (OR = 1.045. Length of CHD diagnosis was predictive of self-care type (experts OR=1.479; inconsistent OR=1.800).

Conclusions:
This typology suggests that targeted self-care interventions should focus on improving self-efficacy in self-care within the context of work especially in those with new CHD or low job control. Strategies to motivate change in specific behaviors (e.g., diet and exercise) are particularly important.
Abstract 10458: Improved Outcomes of Cardiopulmonary Resuscitation in Rats Treated With Vagus Nerve Stimulation Through Cholinergic Anti-Inflammatory Pathway
Authors: Sun Peng , Yin Lu , Wang Jiangang , Zhao Shen , Yang Zhengfei , Qian Jie , Tang Ziren , Moon Joongbum , Wu Xiaobo , Jena Kline , Tang Wanchun
Published: April 2024

Introduction:
Studies have demonstrated that vagus nerve stimulation (VNS) reduces ischemia reperfusion (I/R) injury. In this study, we investigated the protective effects of VNS in a rat model of cardiopulmonary resuscitation (CPR). We further investigated whether the beneficial effects of VNS were dependent on the alpha 7 nicotinic acetylcholine receptor (α7nAChR).

Methods:
The animals were randomized into 4 groups (n=10 each): (1) CPR group (n=10): the rats underwent 8 mins of untreated ventricular fibrillation (VF) followed by 8 mins of CPR and defibrillation. The right vagus nerve was exteriorized but not stimulated.; (2) VNS group (n=10): the treatment was identical to the CPR group except that VNS was initiated at the beginning of precordial compression and continued for 4 hours after the return of spontaneous circulation(ROSC); (3) MLA group(n=10): the treatment was identical to the VNS group except that α7nAChR antagonist MLA (5mg/kg) was administered intraperitoneally (IP) 15 mins prior to VF; (4) GTS group(n=10): the treatment was identical to the CPR group except that α7nAChR agonist GTS-21 (5mg/kg) was IP injected 30 mins before VF. Blood gases, post resuscitation myocardial and cerebral function and the duration of survival were monitored in all animals.

Results:
There were no differences in mean arterial pressure among 4 groups. Significantly better post-resuscitation myocardial and cerebral functions and longer durations of survival were observed in VNS-treated animals, and these protective effects of VNS could be abolished by MLA and imitated by GTS-21 indicating that these beneficial effects might be dependent on a7nAChR (Figure *P<0.05 vs CPR, **P<0.01 vs CPR, ##P<0.01 vs MLA). In addition, VNS decreased the number of electric shocks and the length of CPR duration.

Conclusion:
VNS improves the outcomes after CPR and cholinergic anti-inflammatory pathway via α7nAChR plays an important role during CPR.
Abstract 10808: Clusterin Up-regulation and Akt Pathway Activation Are Key to GATA-4 Mediated Cytoprotection of Mesenchymal Stem Cells Against Ischemia Injury
Authors: Yu Bin , Yang Yueting , Wang Yi-gang , Millard Ronald , Ashraf Muhammad , Xu Meifeng
Published: April 2024

Clusterin (Clu) is a stress-responding protein with multiple biological functions, including the inhibition of apoptosis and inflammation. Our preliminary microarray studies show that clusterin was prominently upregulated in mesenchymal stem cells (MSCs) overexpressing GATA-4 (MSC
GATA-4
). Here, we directly investigate whether the upregulation of clusterin is involved in GATA-4 mediated cytoprotection.

Methods:
MSCs harvested from bone marrow of SD rats were transduced with GATA-4. The expression of clusterin in MSCs was documented by real-time PCR and western blotting. Simulation of ischemia was achieved by MSCs exposure to a hypoxic environment. Lactate dehydrogenase (LDH) released from MSCs was served as a biomarker of cell injury and MTT uptake was used to estimate cell viability. Mitochondrial function was assessed using mitochondrial membrane potential (ΔΨm) and caspase 3/7 activity.

Results:
(1) Clusterin expression was up-regulated in MSC
GATA-4
compared to control MSCs which transfected with empty-vector (MSC
Null
) (
Fig. A1 - A2
). MSC
GATA-4
were tolerant to 72 h hypoxia exposure; expressed as less LDH release and higher MTT uptake (
Fig. A3
). This protection was abrogated by transfecting with Clu-siRNA (
Fig. A4 - A5
). (2) Exogenous clusterin significantly decreased LDH release and increased MSC survival in hypoxic environment. Moreover, ΔΨm was maintained and caspase 3/7 activity was reduced by exogenous clusterin in a concentration-dependent manner
(Fig. B
). (3) p-Akt expression in MSCs was upregulated following pre-treated with clusterin, although there was no significant change in total Akt (
Fig. C1 - C2
). Moreover, cytoprotection mediated by clusterin (2μM/ml) was partially abrogated by Akt inhibitor LY294002 (5μMml) (
Fig. C3
).

Conclusions:
Up-regulation of clusterin and activation of Akt signaling pathway is involved in GATA-4 mediated cytoprotection consequent to hypoxia stress.
Abstract 10868: Prognostic Value of Fragmented QRS Localization for Myocardial Ischemia and Left Ventricular Dyssynchrony: Analysis Using Semiconductor Single Photon Emission Computed Tomography
Authors: Shimizu Masato , Fujii Hiroyuki , Yamawake Noriyoshi , Nishizaki Mitsuhiro
Published: April 2024

Introduction:
Fragmented QRS (fQRS) in 12-lead electrocardiography is reported to be a predictor of cardiac prognosis in ischemic heart disease. In contrast, certain studies have reported that fQRS is associated with cardiac resynchronization therapy response. However, few studies have evaluated the diagnostic performance of local fQRS using semiconductor single photon emission computed tomography (SPECT).

Hypothesis:
fQRS is a powerful indicator of anterior myocardial ischemia and left ventricular (LV) dyssynchrony.

Methods:
A total of 740 consecutive sinus rhythm patients with various cardiac diseases underwent SPECT with adenosine stress. The local fQRS was classified into I/aVL/V5-6 (lateral), II/III/aVF (inferior), and V1-4 (anterior). Cases with wide QRS (>120ms), obvious right bundle branch block, and where fQRS existed in multi-classes were excluded. A 17-segment model of myocardial perfusion SPECT was divided into 3 areas: anterior, inferior, and lateral. Each summed score at rest (SRS), under stress (SSS), and the difference (SDS) was calculated.

Results:
fQRS was present in 82 cases (lateral, 13; anterior, 15; inferior, 54) and analysis of variance showed that anterior SSS was significantly higher in anterior fQRS cases (p=0.012). Histogram bandwidth of LV contraction onset - a known dyssynchrony parameter - was significantly higher in lateral fQRS cases (p135 degrees and SD>43 degree, lateral fQRS had a high OR (7.91) with significant 95%CI (2.32-27.0) for indicating the condition.

Conclusions:
fQRS in anterior leads is a significant indicator of anterior wall ischemia; and fQRS in lateral leads is a significant indicator of LV dyssynchrony.
Abstract 10904: Undetectable Serum Cardiac Troponin I Does Not Preclude a Diagnosis of Giant Cell Myocarditis
Authors: Gilotra Nisha A , Minkove Nicole , Bennett Mosi K , Tedford Ryan J , Steenbergen Charles , Halushka Marc K , Judge Daniel P , Russell Stuart D
Published: April 2024

Introduction:
Giant cell myocarditis (GCM) is characterized by a fulminant and life-threatening course requiring prompt attention and advanced therapies. Suspicion for GCM is one of the only class I indications for performing an endomyocardial biopsy (EMB) for unexplained heart failure. GCM involves a polymorphous inflammatory cell infiltrate alongside myocyte damage, but may be missed due to the limitations of EMB. Elevated serum cardiac Troponin I (cTnI) is highly specific and sensitive for cardiac injury. Due to the destructive nature of GCM, cTnI would be expected to be elevated in this condition.

Hypothesis:
We hypothesized that cTnI level is not predictive of GCM on EMB.

Methods:
The Johns Hopkins Hospital EMB database was queried for acute myocarditis cases. Peak cTnI at time of presentation was obtained from the medical record.

Results:
Six patients with GCM were identified (Table 1). Peak cTnI values were: <0.06, 0.09, 0.32, 1.8, 15.48 and 26.68 ng/mL. The patients with cTnI of <0.06 and 0.09 ng/mL had evidence of extensive myocyte necrosis on biopsy. Five patients required mechanical circulatory support and/or orthotopic heart transplant, four of whom passed away during index hospitalization. Thirty-seven cases of non-giant cell myocarditis were identified (Table 2). cTnI ranged from undetectable to 192 ng/mL (median 0.47 ng/mL; interquartile range: 6.52 ng/mL).

Conclusions:
To our knowledge, no data exist on the role of cTnI in diagnosis and prognosis in GCM. Based on our experience, cTnI cannot be used as a screening tool or prognostic marker in GCM, nor should a negative or low-level troponin influence the decision to perform EMB.
Abstract 10920: Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis
Authors: Sroubek Jakub , Probst Vincent , Mazzanti Andrea , Delise Pietro , Castro Hevia Jesus , Ohkubo Kimie , Zorzi Alessandro , Champagne Jean , Kostopoulou Anna , Yin Xiaoyan , Napolitano Carlo , Milan David J , Wilde Arthur , Sacher Frederic , Borggrefe Martin , Ellinor Patrick T , Theodorakis George , Nault Isabelle , Corrado Domenico , Watanabe Ichiro , Antzelevitch Charles , Allocca Giuseppe , Priori Silvia , Lubitz Steven A
Published: April 2024

Introduction:
The role of programmed ventricular stimulation (PVS) in identifying Brugada syndrome patients at highest risk for sudden death is uncertain.

Objective:
To investigate the utility of PVS to predict future cardiac arrests or ICD therapy for ventricular arrhythmias in Brugada syndrome patients.

Methods:
We performed a systematic review and pooled analysis of prospective observational studies of Brugada syndrome patients with no history of sudden cardiac arrest who underwent PVS. We estimated incidence rates and relative hazards of cardiac arrest or ICD shock.

Results:
We analyzed individual-level data from 8 studies, comprising 1312 patients who experienced 65 cardiac events (median follow-up of 38.3 months). A total of 527 patients were induced into arrhythmias with up to triple extrastimuli. Induction was associated with cardiac events during follow-up (HR 2.66, 95%CI 1.44-4.92, P<0.001). Event risks were inversely proportional to the number of extrastimuli causing induction (HR for each fewer extrastimulus protocol relative to individuals not induced 1.69, 95%CI 1.25-2.29, P<0.001). Annual event rates varied substantially by syncope history, presence of spontaneous type 1 ECG pattern, and arrhythmia induction (0.23%, 95%CI 0.05-0.68 [no induced arrhythmia with up to double extrastimuli]; 0.45%, 95%CI 0.01-2.49 [induced arrhythmia]) and highest risk occurring among individuals with syncope and spontaneous type 1 patterns (2.55%, 95%CI 1.58-3.89 [no induced arrhythmia]; 5.60%, 95%CI 2.98-9.58 [induced arrhythmia]; (
Figure
).

Conclusion:
In Brugada syndrome patients, arrhythmias induced with PVS associate with future ventricular arrhythmia risk. Induction with fewer extrastimuli is associated with higher risk. However, clinical risk factors are important determinants of arrhythmia risk, and lack of induction does not necessarily portend low ventricular arrhythmia risk particularly in patients with high-risk clinical features.
Abstract 10936: Rgs5 Protects Against Vagal Related Bradycardia and Atrial Tachyarrhythmia
Authors: qin mu
Published: April 2024

Background:
The regulator of G-protein signaling 5 (Rgs5), functions as regulator of G protein coupled receptor (GPCR) including muscarinic receptors, has potentially effect on atrial muscarinic receptor activated I
K,Ach
current.

Objective:
To elucidate the effect of regulator of G-protein signaling 5 (Rgs5) on vagal related bradycardia and atrial tachyarrhythmia (ATA) in mice.

Methods and Results:
In the present study, the Rgs5 knockout (KO) mice had decreased LF/HF ratio in spectral measures of heart rate variability, and provoked dramatically exaggerated bradycardia and significantly (P <0.05) prolonged sinus nodal recovery time in response to carbachol (0.1mg/kg, IP). However, cardiac transgenic of human Rgs5 (Rgs5TG) appeared to confer autonomic balance in terms of LF/HF ratio (1.01 ± 0.17), and found to be resistant to carbachol induced bradycardia (Fig.A
1-2
). Compared with those from wild-type (WT) mice, Langendorff perfused hearts from Rgs5KO mice had significantly (P <0.01) abbreviated atrial effective refractory periods (ERP) and increased susceptibility of ATA following administration of acetylcholine (1μM). Whereas Rgs5TG hearts showed significant longer ERP and less ATA inducibility than WT groups (P>0.05). In addition, whole patch clamp analyses of single atrial myocytes revealed that the acetylcholine-regulated potassium current (I
Kach
) was stronger in Rgs5KO than in WT mice. In atrial myocytes (n=8) from Rgs5TG mice, we found a smaller amplitude of I
K,ACh
(P>0.05), but the time of activation and deactivation was shorter than in WT mice (P<0.05)(Fig.B
1-4
). The expression levels of I
KACh
subunits Kir3.1 and Kir3.4 were similar among three groups (P>0.05).

Conclusion:
The results of this study indicate that as a critical regulator of parasympathetic activation in the heart, Rgs5 prevents vagal related bradycardia and ATA through negatively regulating the I
Kach
current.
Abstract 10987: Minimally Invasive Percutaneous Pericardial ICD Placement in an Infant Piglet Model: Head-to-Head Comparison With an Open Surgical Thoracotomy Approach
Authors: Clark Bradley C , Davis Tanya D , El-Sayed Ahmed Magdy M , Ishibashi Nobuyuki , Jordan Christopher P , Kane Timothy D , Kim Peter C , Krieger Axel , Nath Dilip S , Opfermann Justin D , Berul Charles I
Published: April 2024

Introduction:
Epicardial ICD placement in infants, small children, and patients with complex cardiac anatomy requires an open thoracotomy and is associated with increased pain, longer length of stay, and higher cost. We compared a surgical epicardial approach with percutaneous pericardial placement of an ICD lead system in an infant piglet model.

Methods:
Animals were randomized to undergo either epicardial placement by direct suture fixation through a left mini-thoracotomy or minimally invasive pericardial insertion with thoracoscopic visualization. Pericardial access was achieved through sub-xiphoid insertion of a pericardiocentesis needle followed by 7-French sheath insertion over a guide wire. An ICD lead (Medtronic) was passed through the sheath and fixed to the epicardium. In both groups, the lead was connected to an ICD generator placed within a sub-rectus abdominal pocket. Lead testing and defibrillation threshold testing (DFT) were performed. All piglets underwent a 2 week survival period followed by repeat lead testing and DFT prior to euthanasia.

Results:
Minimally invasive pericardial placement was performed in 8 piglets and surgical epicardial placement in 7 piglets (3-4 kg) without procedural morbidity or mortality. Mean initial DFT was 10.5 Joules (range 3-28J) in the pericardial group and 10 Joules (range 5-35J) in the surgical group (p = N.S.). After the survival period, mean DFT was 12 Joules (range 3-20J) in the pericardial group and 12.3 Joules (range 3-35J) in the surgical group (p = N.S.). All lead and shock impedances, R-wave amplitudes, and ventricular pacing thresholds remained stable throughout the survival period and showed no significant difference between the two groups.

Conclusions:
Compared to surgically placed epicardial ICD leads, percutaneous pericardial placement shows a nearly identical ability to effectively defibrillate the heart and has demonstrated similar lead stability. This can provide a means of defibrillator implantation without the need for open chest approach and its attendant pain and morbidity. With continued operator experience, the minimally invasive method may provide a viable alternative to epicardial ICD lead placement in infants, children, and adults at risk for sudden cardiac death.
Abstract 11490: Increased Late Sodium Current Contributes to Excess Prolongation of Canine Ventricular Repolarization Induced by Dofetilide
Authors: Qiu Xiaoliang(Shawn) , Chauveau Samuel , Evgeny Anyukhovsky P , Rahim Tania , Jiang Ya-Ping , Harleton Erin R , Feinmark Steven J , Lin Richard Z , Rosen Tove S , Cohen Ira S , Rosen Michael R
Published: April 2024

Introduction:
Drugs are screened for delayed rectifier potassium current (IKr) blockade to predict QT prolongation and proarrhythmic potential, but recent in vitro cell studies have shown chronic exposure (hours) to some IKr blockers (e.g. dofetilide, D) prolongs repolarization by increasing late sodium current (INa-L) via PI3 kinase inhibition.

Hypothesis:
Chronic D administration to intact dogs prolongs repolarization by blocking IKr and increasing INa-L.

Methods:
We continuously infused D into 6 dogs (6-9 μg/kg bolus+6-9 μg/kg/h IV infusion) for 7h, maintaining D plasma levels within the therapeutic range(2.4±0.2 to 5.2±0.6ng/ml). Acute and chronic D effects on action potential duration (APD) were studied in canine left ventricular (LV) subendocardial slabs using microelectrode techniques.

Results:
D infusion increased QTc and repolarization time (RT) continuously from baseline to 7h (Table). The INa-L blocker lidocaine (2mg/kg bolus) reduced all variables at 6.5h>0.5h (Table) (e.g. QTc: 19±2% vs 8±1%, P<.05). Chronic, but not acute, D increased apico-basal dispersion of RT, and lidocaine significantly attenuated this effect (Table). In LV subendocardium in vitro, D superfusion (0.2 μM) increased APD at 90% repolarization (APD90) from 232±8ms at baseline to 303±7 at 0.5h (P<.05) and 372±6 at 6.5h (P<.05 vs .5h)(n=6). Lidocaine (20 μM) decreased APD90 by 8±1% at 0.5h and 23±1% at 6.5h (P<.05). In comparison, moxifloxacin (100 μM), an IKr blocker with no effect on INa-L increased APD90 from 216±3ms to 282±5 at 1h (P<.05), and 289±5 at 6.5h (P>.05 vs 1h). Lidocaine reduced APD90 equally by 8% at both 1h and 6.5h (P>.05 for 1h vs 6.5h).

Conclusions:
Chronic D prolongs ventricular repolarization by blocking Ikr and increasing INa-L. Acquired LQT during chronic D dosing may be attributable to the INa-L increase, highlighting the need to include time and INa-L in evaluating the PI3K inhibition-derived proarrhythmic potential of new drugs.
Abstract 11654: Association of Pulmonary Vein Diameters With Atrial Fibrillation Recurrence Following Ablation
Authors: Mints Yuliya , Gucuk Ipek Esra , Habibi Mohammadali , Chrispin Jonathan , Marine Joseph E , Rickard Jack , Spragg David , Zimmerman Stefan , Calkins Hugh , Nazarian Saman
Published: April 2024

Background:
Pulmonary vein (PV) isolation is commonly used for treatment of drug-refractory symptomatic atrial fibrillation (AF). Previous studies have reported contradictory results regarding the association of PV structure and AF recurrence following ablation. We sought to examine the association of PV diameter with AF recurrence following ablation.

Methods:
We conducted a retrospective cohort study of 132 patients with AF that had undergone initial PV isolation. Cardiac magnetic resonance angiography was performed prior to ablation, and pulmonary vein and left atrial dimensions were measured. In the presence of a left common PV trunk, the diameter of the superior vein branch was measured after the ostium. Recurrence of AF was documented using scheduled (6 and 12 months) and symptom-prompted electrocardiography.

Results:
The average age was 59.7±9.8 years. Of all patients 78.8% were male, 88.6% were Caucasian, and 45.5% had persistent AF. Atrial fibrillation recurrence was noted in 48 (36%) of patients at 1 year. Due to significant co-linearity among PV diameters within the same individual, the left superior PV (LSPV) diameter was used as a surrogate for all veins. In a multivariable Cox proportional hazards model adjusting for left atrial volume, AF persistence, age, and gender, LSPV diameter > 90
th
percentile (22 mm) was independently associated with AF recurrence (Figure, Hazard Ratio 1.89 ± 0.57, p=0.035).

Conclusion:
Increased PV diameter is associated with AF recurrence following PV isolation. Tools to improve the efficiency and permanence of electrical isolation for large diameter PVs will likely improve procedural efficacy.

Figure.
The hazard ratio plot demonstrates that as the LSPV diameter increases, the hazard ratio of AF recurrence after PVI increases.
Abstract 11724: Premature Atrial Contraction Frequency is not Associated With Cerebral Infarcts: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Chen Lin Y , Agarwal Sunil K , Norby Faye L , Gottesman Rebecca F , Loehr Laura R , Soliman Elsayed Z , Mosley Thomas H , Folsom Aaron R , Coresh Josef , Alonso Alvaro
Published: April 2024

Background:
Premature atrial contractions (PACs) have been shown to predict incident atrial fibrillation (AF). However, the association between PAC frequency and risk of ischemic stroke is less well-characterized. We evaluated the cross-sectional association between PAC frequency and cerebral infarcts on brain MRIs in a sample of participants from the ARIC study, a community-based prospective cohort study.

Hypothesis:
We hypothesized that higher PAC frequency is associated with higher odds of cerebral infarcts.

Methods:
We included 323 (mean age [SD], 78.8 [5.1] years; 52.9% female) participants who underwent brain MRI scans, and ≥2 days of heart rhythm recording using the Zio
®
Patch (a non-invasive, 2-week continuous ECG monitor) in July 2013-March 2014. PAC frequency was defined as the number of PACs per hour, averaged over the entire monitoring period. Definitions of MRI-diagnosed brain infarcts are given in the Table . We used multivariable logistic regression to assess the association of PAC frequency tertiles with cerebral infarcts on MRI scans.

Results:
The mean wear and analysis time of the Zio
®
Patch were 13.1 [2.1] and 12.7 [2.3] days, respectively. Twenty-six (8%) participants had AF detected by the Zio
®
Patch. Higher PAC frequency was not associated with higher odds of cerebral infarcts (Table). A sex- and age-adjusted logistic regression modeling PAC frequency with a restricted cubic spline confirmed the lack of association with cerebral infarcts.

Conclusions:
Although PACs are a precursor to AF, and the risk factors for PACs are largely similar to AF, higher PAC frequency is not related to higher odds of cerebral infarcts. This finding suggests that the disorganized rhythm of AF or the presence of some other factor such as left atrial enlargement or dysfunction may be necessary for the pathogenesis of ischemic stroke.
Abstract 11913: Early Nonadherence With Dabigatran and Rivaroxaban in Patients With Atrial Fibrillation
Authors: Jackevicius Cynthia , Tsadok Meytal , Essebag Vidal , Atzema Clare , Eisenberg Mark J , Tu Jack V , Lu Lingyun , Rahme Elhame , Humphries Karin H , Ho P. Michael , Turakhia Mintu , Behlouli Hassan , Zhou Limei , Pilote Louise
Published: April 2024

Background:
Dabigatran and rivaroxaban are novel oral anticoagulants (NOACs) approved recently for stroke prevention in atrial fibrillation (AF). Although NOACs are more convenient than warfarin, their lack of monitoring, and for dabigatran, dosing frequency may predispose patients to nonadherence. Limited information is available on the adherence rates and related clinical outcomes for dabigatran and rivaroxaban in clinical practice.

Methods:
We conducted a population-based cohort study using administrative data of patients aged 65 years and over with AF, linking hospital discharge abstract and prescription claims databases in Ontario, Canada from April 2012 to March 2014. Nonadherence was measured as proportion of patients discontinuing dabigatran or rivaroxaban, defined as a gap in dabigatran or rivaroxaban prescription for ≥14 days within the first 6 months of therapy, and time to discontinuation. A multivariate Cox proportional hazards model was used to examine the association between drug discontinuation at any time, and the composite outcome of hospitalization for stroke, or death.

Results:
The cohort consisted of 15,857 dabigatran users and 10,119 rivaroxaban users, with women comprising 52% of each medication group. Mean age was 80.7±6.7 years for dabigatran, and 77.0±7.1 years for rivaroxaban patients. At 6-months, 36.5% of patients discontinued dabigatran (110mg: 37.4%; 150mg: 34.1%), while 32.1% of patients discontinued rivaroxaban. Median time to discontinuation was 240 days (IQR: 78-523) for dabigatran and 140 days (IQR: 52-283) for rivaroxaban. Risk of the composite outcome (stroke or death) was significantly higher for those who discontinued dabigatran [HR 1.78 (95% CI 1.62-1.95);p<0.0001] or discontinued rivaroxaban [HR 3.07 (95% CI 2.54-3.72);p<0.0001] compared with those who did not discontinue the medication.

Conclusions:
Within 6 months of initiation, discontinuation rates are high in clinical practice, with 1 in 4 patients discontinuing dabigatran, and 1 in 3 patients discontinuing rivaroxaban. There is an association between nonadherence with either dabigatran or rivaroxaban and significantly worse clinical outcomes following medication discontinuation.
Abstract 11940: Aortic Complications Associated With Pregnancy in Marfan Syndrome: The NHLBI GenTAC Registry
Authors: Roman Mary J , Whitworth Ryan E , Bavaria Joseph E , Devereux Richard B , Dietz Hal , Holmes Kathryn , Eagle Kim A , LeMaire Scott A , Morris Shaine A , Pyeritz Reed , Ravekes William J , Silberbach Michael
Published: April 2024

Background:
Definition of pregnancy risk in women with Marfan syndrome (MFS) has been confounded by ascertainment bias, lack of imaging data, small sample size, and inclusion of women without a known MFS diagnosis before a pregnancy complication. To lessen these limitations, we analyzed MFS women participating in the large GenTAC Registry.

Results:
Among 184 women in whom pregnancy information was available, 94 women (51%) had a total of 227 pregnancies (average 2.5, range 1-6). Compared to MFS women who never became pregnant, those with pregnancies were older at time of MFS diagnosis (27 vs. 13 years, p<0.0001) and at time of GenTAC enrollment (47 vs. 37 years, p<0.0001). When comparing ever-pregnant to never-pregnant women with MFS at the time of registry entry, higher historical rates of aortic dissection and prophylactic proximal aortic surgery were observed (24/94 [25.5%] vs. 13/90 [14.4%], p=0.068 and 15/94 [16.0%] vs. 4/90 [4.4%], p=0.014; respectively).

Among the 94 MFS women with pregnancies, 10 (10.6%) experienced a pregnancy-related aortic complication (4 Type A and 3 Type B dissections, one coronary artery dissection, and 2 with significant [≥3 mm] aortic growth, 1 of whom required post-partum prophylactic surgery). Four of the aortic dissections, including all 3 Type B, and the coronary dissection occurred in the post-partum period. Only 3 of 7 women (43%) with an aortic dissection related to pregnancy were aware of their MFS diagnosis before pregnancy. Women with and without pregnancy-associated aortic complications did not differ in phenotypic features. The rate of aortic dissection was higher during pregnancy + post-partum period (3.5 per 100 person-years vs. 0.8 per 100 person-years, odds ratio 4.6 [95% confidence interval 2.1-10.1], p=0.0002).

Conclusions:
Pregnancy in MFS is associated with an increased risk of aortic dissection, both Types A and B, particularly in the immediate post-partum period, and more frequent prophylactic surgery. Lack of knowledge of underlying MFS diagnosis before aortic dissection is a major contributing factor. These findings underscore the need for early diagnosis, pre-pregnancy risk counselling, and multi-disciplinary peri-partum management.
Abstract 11953: Predictors of In-Hospital Mortality Among Left Ventricular Assist Device Recipients in the United States: A National Inpatient Sample Perspective
Authors: Mahmoud Ahmed M , Abbas Ali , Draganov Peter , Aranda Juan , Ahmed Mustafa
Published: April 2024

Background:
A remarkable increase in the rate of left ventricular assist devices (LVAD) placement has occurred in recent years. Despite increased utilization, there is a continued need to define the changing incidence of in-hospital mortality and their predictors.

Methods:
From 2009 to 2011, National Inpatient Sample database was utilized to include all adult patients with admission diagnosis codes of congestive heart failure and procedure codes for left ventricular assist device (37.66). Patients who underwent LVAD and IABP or OHT placement were excluded from the analysis. Information about demographics, insurance, year of admission, and hospital characteristics, comorbidities and acute in hospital complications were abstracted. Using in-hospital death as our outcome, variables that achieved statistical significance (p <0.05) using Chi square testing were included in a multivariable regression analysis.

Results:
A total of 4,869 patients had LVAD placement with a mean age was 56 (49-65) years. 57% of the patients were Caucasian and near half of the patients (46%) were on Medicare insurance. Ninety eight percent of the LVAD placement was performed in teaching hospitals. The overall mortality rate was 12.4%, with reduced mortality in 2010 and 2011 as compared to 2009. The presence of acute kidney injury (AKI) requiring hemodialysis (HD) was associated with the highest risk of in-hospital death [OR 21, CI 95% 14.4-30.8, p<0.001]. Other predictors of mortality included age, insurance status, end stage renal disease (ESRD), intubation and mechanical ventilation, pulmonary embolism, disseminated intravascular coagulopathy (DIC), severe liver disease and gastro-intestinal bleeding (GIB). Table 1

Conclusion:
In this nationwide analysis, overall in-hospital mortality occurred in 12% of the patients following LVAD placement. The presence of older age, low socio-economic status, AKI, ESRD, GIB and DIC are associated with worse outcome following LVAD placement.
Abstract 12101: Family History of Coronary Heart Disease and Coronary Artery Calcium in South Asians and 4 Other Racial/Ethnic Groups in the US: The Mediators of Atherosclerosis in South Asians Living in America study and the Multi-Ethnic Study of Atherosclerosis
Authors: Patel Jaideep , Cainzos-Achirica Miguel , Kandula Namratha , Kanaya Alka , Blumenthal Roger S , Nasir Khurram , Blaha Michael J , Joshi Parag H
Published: April 2024

Introduction:
High coronary heart disease (CHD) rates among South Asians (SAs) are not fully explained by traditional risk factors. The association of a family history of CHD (FH) with subclinical atherosclerosis as measured by coronary artery calcium (CAC) in SAs is unknown.

Hypothesis:
FH is significantly and independently associated with CAC presence and burden in SAs and other ethnicities.

Methods:
We included all participants aged 45-84 years from two community-based populations: the MASALA study of SAs and the MESA study of Non-Hispanic Whites (NHWs), African Americans (AAs), Chinese Americans (CAs), and Hispanics (HPs). All participants underwent baseline CAC scanning. FH was defined as a self-reported history of CHD in a first-degree relative. We used multivariable regression models to assess the association of FH with CAC (>0 and >100) and likelihood ratio tests to assess the incremental predictive ability of FH to identify CAC (>0 and >100) when added to the 2013 ACC/AHA ASCVD risk estimate in each racial/ethnic group.

Results:
Baseline demographics are shown in the table. NHWs, AAs, and HPs with a FH had a significantly higher proportion of CAC>0 and CAC>100 than those without FH. In unadjusted and multivariable analyses, FH was significantly associated with CAC burden in NHWs, AAs, and HPs, but not in CAs or SAs (Table). Similarly, FH significantly added to the ASCVD risk estimate in predicting prevalent CAC>0 and CAC>100 in NHWs, AAs, and HPs (p-values <0.01 for all), but not in CAs (p-value 0.151 and 0.362) or in SAs (p-value 0.778 and 0.216, respectively). In a sensitivity analysis, FH was significantly associated with very high CAC>400 in SAs, but not in CAs.

Conclusion:
FH was strongly and independently associated with CAC burden in NHWs, AAs, and HPs; this association was weaker and non-significant in CAs and SA in the US. Understanding the reasons behind these findings will require evaluation in larger populations of CAs and SAs with detailed ascertainment of FH.
Abstract 12134: Relationship of Plasma Aldosterone Concentration to Cardiovascular Events Following Acute Coronary Syndrome in Patients Without Advanced Heart Failure
Authors: Pitts Reynaria , Gunzburger Elise , Kallend David , Olsson Anders , McMurray John J , Kittelson John , Schwartz Gregory G
Published: April 2024

Background:
Aldosterone may have adverse effects in myocardium and vessel wall, influencing cardiovascular (CV) risk. Mineralocorticoid antagonists reduce CV risk in patients with acute myocardial infarction (MI) complicated by heart failure (HF) or chronic heart failure with reduced ejection fraction (EF). It is uncertain whether aldosterone levels predict adverse cardiovascular outcomes in patients with acute coronary syndrome (ACS), but without advanced HF.

Methods:
The dal-Outcomes trial evaluated CV effects of the cholesteryl ester transfer protein inhibitor, dalcetrapib, after ACS. Patients with NYHA class II (with EF< 40%), III, or IV HF were excluded. In a subgroup of 4,073 patients, aldosterone was measured at randomization, 4-12 weeks after ACS. Primary outcomes, assessed over a median follow-up of 37 months, were coronary heart disease death, non-fatal MI, stroke, unstable angina, or resuscitated cardiac arrest; these occurred in 366 patients (9.0%). Hospitalization for heart failure, a secondary outcome, occurred in 72 patients (1.8%).

Results:
Baseline median aldosterone was 267 (IQR of 201, 371) pmol/L. Kaplan-Meier curves showed no difference in risk of a primary outcome across quartiles of aldosterone (Figure). Cox proportional hazards analysis, adjusted for demographic, clinical, laboratory, and drug treatment variables did not show a significant relationship of aldosterone to risk of a primary endpoint (for doubling of aldosterone, HR 0.95, 95% CI 0.81-1.12, p=0.55). However, after adjustment, a doubling of aldosterone was significantly associated with HF hospitalizations (HR 1.55, 95% CI 1.09-2.2, p=0.015).

Conclusion:
In patients with recent ACS but without advanced HF, aldosterone does not predict major ischemic CV events, but appears to mark an increased risk of HF hospitalization.
Abstract 12264: A Risk Score for the Prediction of Atrial Fibrillation in the Japanese Community: The Suita Study
Authors: Kokubo Yoshihiro , Watanabe Makoto , Higashiyama Aya , Nakao Yoko M , Watanabe Takuya , Takegami Misa , Kusano Kengo , Kamakura Shiro , Miyamoto Yoshihiro
Published: April 2024

Introduction:
Atrial fibrillation (AF) is the most common chronic arrhythmia and is a strong risk factor for all-cause mortality and stroke. However, there is no risk score for incident AF in non-Westerners.

Aim:
We aimed to develop and validate a risk score for AF incidence in a Japanese general population.

Methods:
A total of 6,906 participants (30-84 years old) initially free of AF were prospectively followed up for incident AF in the Suita Study. Standard 12-lead ECGs were obtained from all subjects in the supine position. Each record was coded independently by 2 well-trained physicians. Participants were diagnosed with AF if AF or atrial flutter was present on ECGs obtained during a biannual routine health examination or if AF was indicated as a present illness by either annual questionnaires responses or participants' medical records during follow-up. Cox proportional hazard ratios were analyzed after adjusting for cardiovascular risk factors at baseline. The model discrimination was evaluated by the area under the receiver operating characteristic curve.

Results:
In 88,663 person-years of follow-up, 253 incident AF events occurred. Age, sex, body mass index, valvular disease and/or heart murmur, systolic blood pressure, ischemic heart disease, smoking, and excessive drinking were associated with incident AF (C-statistic 0.73; 95% confidence intervals, 0.70-0.75). The risk scores for participants in their 30s, 40s, 50s, 60s, and 70s, sex (women), smoking 1~19 and ≥20 cigarettes/day, excessive drinking (4 units/day or more of alcohol), systolic prehypertension with overweight or obesity, systolic hypertension with normal weight/overweight or obesity, ischemic heart disease, and valvular disease and/or heart murmur were -6, 0, 6, 18, 27, -6, 2, 5, 5, 6, 5, 10, 7, and 12, respectively. Individuals scoring ≤19 and ≥40 points, for example, had ≤3.5% and ≥8.5% predicted probability of developing AF in 10 years, respectively.

Conclusions:
We developed a risk score to predict 10-year incident AF risk using variables that are easily available in healthy examination in Japan. This risk score can be useful for a person with higher risk of AF in order to consult a doctor and encourage lifestyle improvements before onset of AF.
Abstract 12421: Association Between Distance-to-index And Phenotype In Familial Hypercholesterolemia
Authors: Besseling Joost , Huijgen Roeland , Martin Seth S , Hutten Barbara A , Kastelein John J , Hovingh Gerard K
Published: April 2024

Introduction:
Familial hypercholesterolemia (FH) is a genetic disorder characterized by severely increased levels of low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease (CVD). Early identification of patients is warranted, to initiate preventive therapy. Genetic cascade screening has been exploited during the last two decades in the Netherlands. However, since the cascade starts with an FH patient with high clinical suspicion, the FH phenotype might deflate in family members with FH who are identified in subsequent steps of cascade testing. We set out to test this hypothesis.

Methods:
We analyzed heterozygous FH patients identified by the genetic cascade screening program in the Netherlands from 1994 to 2014. A cascade starts with identification of a genetically proven FH patient (“index patient”) followed by testing in first degree relatives. If a mutation is found in one of them, their first degree relatives are tested as well, and so on. The association between exposure (i.e. distance to the index [1st, 2nd, 3rd or 4th or more degree family member]) and primary outcome (i.e., LDL-C level) was evaluated using linear regression models. Second, we tested whether increasing distance-to-index was associated with decreasing CVD risk by means of Cox proportional hazard models. In all regression analyses we adjusted for potential confounders and family relations.

Results:
A total of 64,171 persons participated in the screening program, of whom 26,176 had molecularly defined heterozygous FH. Of these, 4,531 (17%) were index patients. The distance-to-index could be determined in 13,392 (61%) of the remaining FH patients. Mean (± standard error) levels of LDL-C modestly decreased with increasing distance-to-index: 211 (56), 199 (54), 189 (52) and 178 (51) mg/dL in 1st, 2nd, 3rd and 4th or more, respectively (p-for-trend: 0.005). The adjusted hazard ratio of increasing distance-to-index for CVD was 0.92 (95% CI: 0.82 - 1.03).

Conclusions:
To our knowledge, this is the first study ever investigating the association between distance-to-index and the phenotype of a monogenetic disorder. The absence of a strong association between distance-to-index LDL-C or and CVD risk in FH lends support for genetic cascade testing.
Abstract 12479: CHA2DS2-VASc Clinical Predictors Are Associated With Stroke in Patients With Acute Coronary Syndrome Independently of Atrial Fibrillation: A Systematic Review and Meta-analysis on 690.000 Patients
Authors: Guerra Federico , Scappini Lorena , Campo Gianluca C , Pavasini Rita , Capucci Alessandro
Published: April 2024

Introduction:
Stroke is a rare but serious complication of acute coronary syndrome (ACS), its incidence depending on well defined risk factors.

Hypothesis:
To test whether clinical variables included in the CHA2DS2-VASc score keep their predictive value even in patients with recent ACS, regardless of atrial fibrillation (AF) presence.

Methods:
Meta-analysis was performed according to the PRISMA guidelines. MEDLINE and EMBASE were searched using the following query: (“stroke OR embolism”) AND “acute coronary syndrome” NOT “atrial fibrillation”. At the end of the selection process, 21 papers (10 randomized clinical trials and 11 observational studies) were entered into the meta-analysis. The following variables were taken into account: heart failure, hypertension, age, diabetes mellitus, previous stroke, gender and previous vascular disease. RRs was used as the main effect size. Because of the large heterogeneity in studies’ characteristics, a random-effects model was used and each variable was tested separately for randomized clinical trials and for observational studies before entering the pooled analysis. The interaction between clinical features and presence of atrial fibrillation was tested by performing a random effect meta-regression.

Results:
The whole cohort included 690.309 patients. Median follow-up was 9 months. Advanced age and previous stroke resulted as the most important risk factors for stroke (RR 5.89. 95% CI 4.92-6.86 for advanced age and RR 2.83. 95% CI 2.36-3.38 for previous stroke), in accordance with the two-point value that both of them have in the CHA2DS2-VASc score. All other factors were positively associated with stroke, albeit RRs were lower (heart failure RR 1.57 95% CI 1.32-1.86; hypertension RR 1.19; 95% CI 1.13-1.26; female gender RR 1.26, 95% CI 1.18-1.36; diabetes mellitus RR 1.35, 95% CI 1.25-1.46; vascular disease RR 1.35, 95% CI 1.11-1.63). Although AF confirmed its association with stroke (RR 2.13, 95% CI 1.82-2.49), its interaction on aforementioned variables was not significant.

Conclusions:
All risk factors included in the CHA2DS2-VASc score are associated with stroke in patients with ACS, making it an useful tool for risk stratification in patients with ACS, regardless of AF presence.
Abstract 12508: Tuning the Heart Rate Recovery For Age
Authors: Sydó Nóra , Sydó Tibor , Gonzalez Carta Karina A , Murphy Joseph G , Merkely Béla , Allison Thomas G
Published: April 2024

Introduction:
Exercise parameters such as peak heart rate (HR) are generally adjusted for age, whereas HR recovery is generally given as an absolute value: < 13 bpm at 1 minute post-peak exercise being abnormal.

Hypothesis:
We analyzed a large cohort of patients to determine the impact of age on HR recovery (HRRec) and if the prognostic performance of HRRec is improved by adjustment for age.

Methods:
Non-imaging exercise tests performed on patients aged 30-79 years from 1993 to 2010 were included. Patients with known cardiovascular diseases were excluded. Patients were assigned to 5 groups according to age: 30-39, 40-49, 50-59, 60-69, and 70-79. Mortality was reported according to HRRec during the first minute of active recovery using Cox regression analysis. Mortality was determined from Minnesota and National Death Indices.

Results:
22,643 patients (64 % male) were included. The median HRRec in the age groups with IQR were as follows: 30-39: 20 [15-26]; 40-49: 19 [14-25]; 50-59: 18 [13-23]; 60-69: 15 [10-20]; and 70-79: 11 [6-16]. There were 1566 deaths (6.9%) over a mean follow-up of 11.8 ± 5.0 years. HRRec of 13 would fall at the 17
th
percentile for patients 30-39 years old, but this increased to the 20
th
, 27
th
, 40
th
, and 60
th
percentiles with increasing age group. The mortality in age groups according to HRRec is shown in the Figure. For age groups 30-39 and 40-49, the hazard ratio for mortality at a HRRec of 11-12 bpm (i.e. just below the standard of 13) versus patients with a HRRec of ≥ 20 bpm was > 2.0. For age 50-59 and 60-69, however, a HRRec of < 11 bpm is necessary to obtain a doubling of risk, and for age 70-79 a HRRec of < 9 bpm is necessary.

Conclusions:
HRRec decreases significantly with age. The performance of abnormal HRRec defined as < 13 bpm is inconsistent across age groups. To standardize the ability of HRRec to identify at least a 2.0-fold increased risk, lowering the cup-point to < 11 bpm for ages 50-59 and 60-69 and < 9 bpm for age 70-79 is required.