bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11571: Whole Exome Sequencing in Familial Hypobetalipoproteinemia
Authors: Tada Hayato , Kawashiri Masa-aki , Nohara Atsushi , Inazu Akihiro , Mabuchi Hiroshi , Yamagishi Masakazu
Published: July 2021

Background:
Whole exome sequencing (WES) has shown ~30% success in the diagnosis of Mendelian disorders. Few data exists regarding clinical application of WES for the molecular diagnosis of familial hypobetalipoproteinemia (FHBL), which is characterized as extremely low LDL cholesterol level.

Methods:
WES was performed on 36 individuals including 32 patients exhibiting low LDL-C (less than 70 mg/dl) primarily, and 4 unaffected family members from 23 families. We filtered out the following variants: 1) Benign variants predicted by SnpEff; 2) Minor allele frequency (MAF) > 1%; 3) Segregation unmatched for the autosomal codominant pattern; 4) C-score < 10 calculated using in silico prediction software named Combined Annotation Dependent Depletion.

Results:
Among 181,404 variants found in those individuals, we found 48,786 nonsense, missense, or splice site variants, of which 14,415 were rare (MAF ≤ 1% or not reported). Filtering assuming autosomal codominant pattern of inheritance combined with the use of C-score, we identified heterozygous mutations in 7 families, and homozygous or compound heterozygous mutations in 4 families within the coding region of APOB gene, eight of which were novel (c.394A>T/p.Lys132*, c.1902_1903delTC/p.Ser634fs, c.2702T>G/p.Met901Arg, c.2946delC/p.Ser982fs, c.4437G>C/p.Leu1479Phe, c.4439_4440delTT/p.Phe1480fs, c.11283C>A/p.Cys3761*, c.11433dupT/p.Glu3812fs). Moreover, we identified compound heterozygous mutations in 1 family within the coding region of PCSK9 gene, one of which was novel (c.1301G>A/p.Arg434Gln).

Conclusion:
WES combined with integrated variant annotation prediction successfully identified causative mutations in patients with FHBL either with APOB gene mutation(s) or PCSK9 gene mutation(s) in 12 among 23 families (52%). Although such comprehensive approach is useful to determine true causative mutations, other strategies are needed to identify novel causative genes, which could potentially lead to the development of novel pharmacological target for dyslipidemia.
Abstract 11616: Effect of a Lifestyle Weight Loss Intervention on Visceral Fat and Glycemic Control Among Individuals With and Without Type 2 Diabetes
Authors: Nam Soohyun , Nam Soohyun , Dobrosielski Devon A , Stewart Kerry J
Published: July 2021

Background:
Though a high amount of visceral fat is associated with insulin resistance, which can lead to type 2 diabetes (T2D) and cardiovascular diseases (CVDs), less is known about whether lifestyle modification (weight loss diet and exercise) induced changes in visceral fat are associated with improvements in glycemia.

Methods:
We randomized 77 individuals aged 35-65 years with T2D or pre-diabetes to 6-months of weight loss diet (D); or D combined with supervised moderate-intensity exercise training (D+E). Study measures were total abdominal, visceral and subcutaneous fat volumes by magnetic resonance imaging, aerobic fitness expressed as VO
2
peak during treadmill testing, body mass index (BMI), and HbA1c levels from blood samples.

Results:
Of 77 subjects (mean age, 54.8±7.8 years; mean BMI, 34.5 ± 4.7 kg/m
2
, women, 77.9%; Whites-65%, Blacks-34%, Asians-1%), n=37 had T2D and n=40 had pre-diabetes. At 6 months, both D and D+E groups improved from baseline (p<0.05 for all) but did not differ in their changes for body weight (D: -6.04 ± 4.54 kg; D+E: -6.68 ± 4.48 kg, p= 0.61 for the group differences in change), abdominal total fat (D: -101.93 ± 68.67 cm
2
; D+E:-104.16 ± 72.37 cm
2
, p= 0.92), visceral fat (D:-25.53 ± 39.44 cm
2
; D+E:,-23.24 ± 35.62 cm
2
, p=0.85), HbA1c (D:0.04 ± 0.46%; D+E:0.03 ± 0.63%, p=0.96), and VO
2
peak (D: 2.26 ± 3.92 ml/kg/min ; D+E:3.71 ± 2.65 ml/kg/min, p=0.11). In a multivariate analysis, adjusting for baseline visceral fat, T2D status, body weight loss and increases in aerobic fitness, a reduction in HbA1c (β=-0.49, p =0.007) was associated with a reduction in visceral fat (R
2
=0.34, p=0.02).

Conclusion:
The key finding was that diet or diet plus exercise-mediated reductions in visceral fat was associated with reduced HbA1c among individuals with T2D or pre-diabetes. These data contribute to growing body of evidence of the benefits of reducing abdominal obesity, in this case, resulting in better glycemic control in T2D and pre-diabetes.
Abstract 11719: “I Have to Live Like I’m Old” - Young Adults’ Perspectives on Managing Hypertension: A Multi-Center Qualitative Study
Authors: Johnson Heather M , Warner Ryan , LaMantia Jamie
Published: July 2021

Introduction:
In the U.S., young adults (18-39 year-olds) have the lowest hypertension control rates among hypertensive adults. The objectives of this multi-center study were to explore young adults’: 1) experiences receiving a hypertension diagnosis, 2) attitudes and beliefs about self-management and antihypertensive medication, and 3) opinions about their healthcare system’s hypertension education materials.

Methods:
Young adults (18-39 year-olds) with a known diagnosis of hypertension were recruited by the Wisconsin Research and Education Network. Two focus groups (one per age range: 18-29 years, 30-39 years) were conducted in three Midwestern practices (academic, rural, and urban clinics). Content analysis was performed.

Results:
In total, 35 young adults (mean: 30 [5.2] years old, 65% female, 47% Black, 45% with at least 1 year of college) identified barriers to managing hypertension. Emergent themes overlapped across ages and geographic regions. A majority of respondents were surprised and angry about a hypertension diagnosis; they expected to develop hypertension, but at a much older age. A hypertension diagnosis altered their “young” self-identity. Suggested behavior changes and antihypertensive medications made them feel “older” in health status. Young adults requested more resources for blood pressure self-monitoring to provide greater autonomy. Contrary to our hypothesis, most young adults disliked using social media or text messaging to support self-management; electronic patient portals were considered more personal, decreasing the risk of peers seeing their hypertension communications. Current hypertension education materials were described as not addressing young adults’ health questions; focus group respondents provided topics of interest.

Conclusions:
Targeting interventions to young adults’ unique needs are important next steps to improve healthcare delivery and hypertension control for young adults.
Abstract 11790: New and Old Cardiovascular Disease Risk Models to Predict Events in HIV Infected Patients
Authors: Raggi Paolo , De Francesco Davide , Zona Stefano , Stentarelli Chiara , Carli Federica , Malagoli Andrea , Maniscardi Marcella , Bellasi Antonio , Guaraldi Giovanni
Published: July 2021

Background:
The high incidence of cardiovascular events in HIV infected patients creates the important challenge of performing an accurate risk assessment and initiating treatment in the most appropriate patients. The new Pooled Equations (PE) recommended by the recent ACC/AHA guidelines have not been tested in HIV infected patients and compared with the older Framingham Risk Score (FRS).

Method:
Cohort of 2,550 HIV infected patients (34% women) followed prospectively for a total of 10,695 patient-years. We compared the 10-year risk of events of 7.5% with PE versus a FRS level of 6%, for the dual purpose of assessing the validity of the new algorithm in HIV and verify whether lowering the threshold of the older algorithm may be equivalent to the new method.

Results:
Mean age was 49.7+/-7 years, and mean HIV exposure was 16.6+/-6 years. Total follow-up was 10,695 patient-years and 67 non-fatal myocardial infarctions and 2 CV deaths were recorded. PE>7.5% and FRS>6% predicted (44/69 and 49/69) and missed (25/69 and 20/69) the same number of true events. The Net Reclassification Index showed that PE>7.5% is weaker than FRS>6% to predict events (7% fewer events predicted) but better to predict non-events (14% more cases predicted to not occur). Table 1 shows the recommendation for statin therapy according to PE and FRS compared to current clinical practice within our institution: the 2 algorithms were not superior to what is currently implemented at our institution.

Conclusions:
In HIV infected patients the new PE>7.5% algorithm performs similarly to a FRS>6% to predict events but is better than the older algorithm to predict non-events. Neither model is superior to clinical practice as a method to select patients who should receive risk reduction therapies. (p-value for comparison of recommended vs actual statin prescription)
Abstract 11818: Mitral Valve Repair for Secondary Mitral Regurgitation In Non-ischemic Dilated Cardiomyopathy is Associated With Left Ventricular Reverse Remodelling and Increase of Forward Flow
Authors: Kamperidis Vasileios , van Wijngaarden Suzanne E , van Rosendael Philippe J , Regeer Madelien V , van der Kley Frank , Sianos Georgios , Ajmone Marsan Nina , Bax Jeroen J , Delgado Victoria
Published: July 2021

Introduction:
It remains unclear whether surgical or transcatheter mitral valve repair for secondary mitral regurgitation (MR) in patients with non-ischemic cardiomyopathy reverse the underlying left ventricular (LV) pathophysiology. Accordingly, the present study evaluated the effect of mitral valve repair on LV performance in this subset of patients.

Methods:
Seventy-six patients (65±14 years old, 43% male) with non-ischemic cardiomyopathy and moderate to severe chronic secondary MR treated successfully with transcatheter or surgical mitral valve repair were evaluated. Transthoracic echocardiography was performed at baseline, discharge and 6-months post-repair.

Results:
After mitral valve repair, LVEF and LV global longitudinal strain (GLS) corrected for LV end-diastolic volume remained unchanged over time (p=0.90 and p=0.96 respectively). In contrast, LV forward flow increased significantly over time (stroke volume index: from 20±7 to 29±8 and 26±8 ml/m2, p<0.001; cardiac index: from 1.50±0.44 to 2.36±0.60 and 2.01±0.48 L/min/m2, p<0.001) (Figure). In addition, LV end-diastolic and end-systolic volume index significantly reduced over time (from 87±42 to 70±33 and 75±39 ml/ m2, p<0.001; and from 60±35 to 50±30 and 53±36 ml/ m2, p=0.004, respectively). These changes were independent of the type of repair.

Conclusions:
Surgical and transcatheter mitral valve repair for secondary MR in patients with non-ischemic dilated cardiomyopathy improved LV forward flow and induced LV reverse remodelling but did not change LV systolic function.
Abstract 11918: The Interplay of Ethnicity and Education With the American Heart Association’s Life’s Simple 7 Metrics: The Baptist Health South Florida Employee Study
Authors: Ogunmoroti Oluseye , Das Sankalp , Utuama Ovie , Younus Adnan , Rouseff Maribeth , Parris Don , Guzman Henry , Ben Taleb Ziyad , Bahelah Raed , Osondu Chukwuemeka U. , Aneni Ehimen , Aziz Muhammad , Oni Ebenezer , Tran Thinh , Maziak Wasim , Feldman Theodore , Agatston Arthur , Veledar Emir , Virani Salim S. , Nasir Khurram
Published: July 2021

Background:
Healthcare disparities are a major public health concern. It is known that ethnicity and educational status independently predict health outcomes. Higher numbers of the American Heart Association's (AHA) ideal Life’s Simple 7 metrics (LS7) are associated with better cardiovascular health. In this study, we investigated the interplay of ethnicity and education on the attainment of ideal cardiovascular health (ICH) among employees of Baptist Health South Florida (BHSF), a large nonprofit health care organization.

Methods:
The data collected during BHSF annual voluntary wellness examination included age, gender, race, ethnicity and education. We assessed cardiovascular health using the LS7 metrics. Components of the LS7 metrics (smoking, physical activity, body mass index, diet, total cholesterol, blood pressure, and blood glucose) were categorized into ideal, intermediate and poor, according to AHA criteria. Study participants who met 6-7 ideal metrics were considered to have attained ICH.

Results:
The study population consisted of 9056 individuals (Mean age 43 ± 12 years, 74% women). Among employees with postgraduate education, 12% of white employees met the ideal for 6-7 LS7 metrics, 15% for Hispanic and 4% for Black employees. For employees with college degrees, the prevalence of 6-7 ideal LS7 metrics was 14%, 16% and 8% for white, Hispanic and black employees respectively (Figure). Overall, the odds of meeting 6-7 ideal LS7 metrics was lower for Hispanic and black employees compared to white employees of similar education (Table). These differences were especially large in those with high school education or less.

Conclusion:
Minorities are at an increased risk of poor cardiovascular health particularly those with the lowest educational achievement. Comprehensive workplace wellness programs that target these groups will improve cardiovascular health and employee productivity, in addition to saving health care costs.
Abstract 11926: An Intensive Heart Health Intervention Can Improve Diet Quality and Reduce Cardiovascular Risk Factors in Individuals Residing in Rural Environments
Authors: Kang JungHee , Biddle Martha J , Lennie Terry A , Moser Debra K
Published: July 2021

Introduction:
Kentucky consistently ranks in the top ten for worst health outcomes in the U.S. Fifty four Kentucky counties are in Appalachia, the region with the nation’s worst social, environmental and health conditions. U.S. Preventive Services Task Force recommends that adults who are overweight or obese and have additional cardiovascular disease (CVD) risk factors be offered intensive behavioral counseling that includes a healthy diet to promote CVD prevention.

Purpose:
To investigate whether an intensive self-management intervention for CVD risk reduction (HeartHealth) improved diet quality and risk factors in persons living in rural Appalachian Kentucky.

Methods:
A sample of 719 adults (age 53±14 years, 74% female, 43±19 years living in Kentucky, 87% overweight or obese) with two or more CVD risk were enrolled in the 12-week HeartHealth intervention that included strategies to improve diet to promote CVD risk reduction. Diet quality was measured by healthy eating index (HEI) calculated from food frequency questionnaires with higher HEI score indicating more healthy diets. The intervention was delivered in small groups using culturally appropriate approaches. Paired t-tests were used to compare HEI scores and CVD risk factors pre- and post-intervention.

Results:
HEI total score increased 8% from 63.3±11.6 to 68.5±11.4 (p<0.005). HEI scores for total fruit; whole fruit; total vegetable; legumes, orange and dark green vegetables; whole grain; and milk increased by 31%, 28%, 7%, 20%, 15%, and 3% ,respectively, post intervention when compared to the baseline (p<0.05). Diet quality for saturated fat; and calories from solid fats, alcoholic beverages and added sugar also improved by 28% and 12%, respectively (p<0.005). Total cholesterol, systolic blood pressure, and hemoglobin A1C levels decreased from 191.8±37.8 to 187.5±36.9 mg/dL, 128.7±16.4 to 125.2±15.6 mmHg, and 5.77±0.96 to 5.70±0.90 %, respectively (p<0.005).

Conclusion:
An intensive behavioral counseling intervention promoted a healthy diet and reduced CVD risk in overweight or obese adults living in a rural socioeconomically distressed environment.
Abstract 11945: Indications and Outcomes Following Transvenous Extraction of ICD versus Pacemaker Leads
Authors: Black-Maier Eric W , Pokorney Sean D , Lewis Robert K , Christian Alexander , Greenfield Ruth A , Hegland Donald D , Daubert James P , Piccini Jonathan P
Published: July 2021

Introduction:
Percutaneous transvenous lead extraction of cardiovascular implantable electronic devices (CIEDs) is increasingly common. Although ICD leads are widely considered to be more difficult to extract than pacemaker leads, there are few direct comparisons.

Methods/Results:
Using a cohort of 368 consecutive patients undergoing lead extraction (dwell time >1 year) between 2005-2012, we compared baseline characteristics/outcomes in extractions involving pacing versus ICD leads. We defined major adverse events (MAE) as any events/complications that required procedural intervention, transfusion, or that resulted in death or serious harm during index hospitalization. Median age was 60.6 yrs and 29.6% were women. There were 136 (37%) pacing lead extractions and 232 (63%) ICD lead extractions. Pacing leads had a longer dwell time (6.14 yrs [IQR 1.2-10.9
]
versus 4.4 yrs [IQR 1.1-6.4], p<0.001) and higher median LVEF (55% [IQR 35-55] vs. 30% [IQR 20-40], p<0.001) compared with ICD lead patients. Indications for pacing and ICD lead extractions included sepsis/endocarditis (21.3% vs. 24.6%, p=0.48), pocket infection (40.4% vs. 34.9%, p=0.29), and lead failure (15.4% vs. 38.8%, p<0.001). There were no significant differences between pacing and ICD lead extractions in median fluoroscopy time (5.5 vs. 8.5 minutes, p=0.86) or femoral bailout rate (4.4% vs. 5.2%, p=0.73). There were similar rates of all-cause MAE during index hospitalization (5.1% vs. 5.6%), death (2.2% vs 3.2%) and clinical success (97.0% vs. 97.0%, p=0.55) in pacemaker and ICD extractions, respectively.

Conclusions:
ICD leads are more commonly extracted relative to pacemaker leads, and this difference is driven by larger numbers of lead failure within ICD leads. Despite much longer dwell times, major adverse events were similar in pacing lead cases compared with ICD extractions.
Abstract 12007: Combination Therapy of Eicosapentaenoic Acid and Pitavastatin for Coronary Plaque Regression Evaluated by Integrated Backscatter Intravascular Ultrasonography: A Randomized Controlled Trial
Authors: Ando Kaoru , Watanabe Tetsu , Daidoji Hyuma , Otaki Yoichiro , Hashimoto Naoto , Kumagai Yu , Hashimoto Naoaki , Narumi Taro , Kadowaki Shinpei , Yamaura Gensai , Wanezaki Masahiro , Funayama Akira , Yashiro Yoshinori , Iwayama Tadateru , Nishiyama Satoshi , Takahashi Hiroki , Arimoto Takanori , Shishido Tetsuro , Miyamoto Takuya , Kubota Isao
Published: July 2021

Introduction:
High intensity statin therapy is established for secondary prevention of coronary heart disease (CHD). However, additional therapy is required to reduce residual risk in CHD patients with aggressive lipid-lowering therapy. Eicosapentaenoic acid (EPA) was reported to be beneficial especially in secondary prevention. The aim of this study was to investigate whether coronary plaque regression and stabilization are reinforced by additional administration of EPA to high dose pitavastatin (PTV) therapy.

Methods:
We enrolled 200 CHD patients who underwent percutaneous coronary intervention in 6 hospitals. Patients were randomly allocated to PTV group (PTV 4 mg/day, n=98) and PTV/EPA group (PTV 4 mg/day and EPA 1800 mg/day, n=102), and prospectively followed for 6 to 8 months. Coronary plaque volume and composition in non-stenting lesion were analyzed by integrated backscatter intravascular ultrasonography at baseline and follow up.

Results:
EPA / arachidonic acid (AA) ratio was significantly increased in PTV/EPA group compared to PTV group at follow up period. Plaque volume and lipid volume were significantly reduced in PTV/EPA group, but not PTV group. There was a significant inverse correlation between change in EPA/AA ratio and changes in plaque volume (r=-0.332, p<0.001). Plaque regression was defined as percent change in plaque volume more than -14.6% according to previous reports. A multivariate logistic analysis demonstrated that the additional administration of EPA was independently associated with plaque regression after adjustment of confounding factors. The prevalence rate of plaque regression was significantly higher in PTV/EPA group than in PTV group (50% vs. 24%, p<0.001).

Conclusions:
Additional administration of EPA to high dose PTV therapy significantly reduced coronary plaque volume, suggesting that combination therapy of EPA and PTV might reduce residual risk in CHD patients with aggressive lipid-lowering therapy.
Abstract 12032: Chronic Kidney Disease Augments Vein Graft Disease Through Interleukin-9-dependent Mechanisms
Authors: Zhang Lisheng , Brian Leigh , Mattocks Natalie K , Gurley Susan B , Freedman Neil J
Published: July 2021

Chronic kidney disease (CKD, glomerular filtration rate (GFR) <60 ml/min/1.73 m
2
) is a powerful independent predictor of cardiovascular events, and CKD increases the risk of vein graft occlusion in CABG patients by 62%. Because CKD impairs clearance of small proteins, we tested the hypothesis that CKD exacerbates vein graft disease by elevating serum levels of critical cytokines that promote neointimal hyperplasia. We modeled CKD in C57BL/6 mice with 5/6ths nephrectomy and modeled vein grafting with IVC-to-carotid interposition grafting. Two wk after 5/6
th
s nephrectomy, GFR was 60±10% less than in sham-operated (control) mice, as determined by FITC-inulin clearance (
p
<0.05); parallel mouse cohorts were used for either blood collection or vein grafting. Of 23 serum cytokines measured by a Luminex-based assay, the following were elevated in CKD (n=12) compared with control mice (n=9): IL-9 (5-fold), IL-12 (1.8-fold), MCP-1 (1.3-fold), TNF (1.3-fold), and RANTES (1.8-fold) (
p
< 0.0003 for each). Four wk after grafting, CKD (n=7) and control mouse (n=7) vein graft neointimas comprised predominantly smooth muscle cells (SMCs), of equivalent prevalence. However, vein graft neointimal area was 4±0.5-fold fold greater in CKD mice: 0.23±0.2 vs. 0.052±0.004 mm
2
(
p
<0.01). By quantitative immunofluorescence, vein grafts from CKD mice showed equivalent neointimal expression of NFκB p65 but ~2-fold greater neointimal activation of NFκB, as judged by phosphorylation of p65 on Ser536 and by expression of VCAM-1 (
p
<0.01). Vein graft protein levels of IL-9 and IL-9 receptor-α were 3.0±0.6- and 1.7±0.3-fold higher in CKD than control mice (
p
<0.01). We then treated CKD mice with IL-9-neutralizing (n=7) or isotype control IgG (n=7) for 4 wk after vein grafting. Control IgG did not affect vein graft neointimal area (0.19±0.02 mm
2
). However, anti-IL-9 IgG treatment reduced vein graft neointimal area 4-fold (to 0.044±0.004 mm
2
,
p
< 0.01), and reduced neointimal levels of phospho-p65, IL-9, and IL-9Rα by 40-50% (
p
<0.05). Of the 5 serum cytokines elevated by CKD, only IL-9 and IL-6 were reduced by anti-IL-9 IgG treatment: 26±3% and 70±20%, respectively (
p
<0.001). We conclude that CKD aggravates vein graft disease dramatically, in large part by elevating plasma levels of IL-9.
Abstract 12088: Low Computed Tomography Attenuation Value of Epicardial Fat is a Useful Marker for Coronary Stenosis
Authors: Sakamoto Aiko , Uehara Masae , Ishizaka Nobukazu , Ando Jiro , Nagai Ryozo , Komuro Issei
Published: July 2021

Background:
Epicardial fat volume (EFV) is recognized as an independent risk factor for coronary atherosclerosis. However, it remains unclear whether the computed tomography (CT) attenuation value of epicardial fat is associated with coronary stenosis.

Methods:
We analyzed the association of epicardial fat CT attenuation value (EFCTA) and EFV with obstructive coronary artery disease (CAD) in 355 patients (203 men; mean age, 68 ± 11 years) who underwent coronary CT angiography. EFCTA was calculated as the mean CT values of 5 regions of interest in epicardial fat.

Results:
A total of 200 (56.3%) patients were judged to have obstructive CAD. There was a strong correlation between EFCTA and EFV (R=-0.618, P<0.001). EFCTA and EFV were significantly lower and higher, respectively, in patients with obstructive CAD (EFCTA, -93.0 HU [interquartile range, IR -101.0 - -84.6]; EFV, 110 mL [IR 83 - 146]) than in those without (EFCTA, -88.8 HU [IR -95.6 - -79.4], P<0.001; EFV, 89 mL [IR 68 - 122], P<0.001). In logistic regression analysis using age and gender as covariates, the lowest EFCTA quartile (<-98.8 HU) was significantly associated with obstructive CAD (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.68 - 6.34, P<0.001). Age- and gender-adjusted logistic regression analysis showed that the highest EFV quartile (≥138 mL) had a significant association with obstructive CAD (OR 2.59, 95% CI 1.35 - 4.96, P=0.004). When age, gender, body mass index, smoking, estimated glomerular filtration rate (eGFR), hypertension, dyslipidemia, diabetes, and quartiles of EFCTA and EFV were used as independent valuables, the association of the lowest EFCTA quartile, but not the highest EFV quartile, with obstructive CAD remained statistically significant (OR 2.48, 95% CI 1.05 - 5.85, P=0.038).

Conclusions:
Low EFCTA was significantly associated with obstructive CAD, independent of traditional cardiovascular risk factors, suggesting that EFCTA may be a novel marker for assessment of CAD.
Abstract 12089: Risk Factors for Major Complications in the Implantation of Epicardial Pacemakers in Neonates and Infants
Authors: Chaouki Ahmad S
Published: July 2021

Introduction:
Complications related to epicardial cardiac rhythm devices in infants have been reported though limited data are available regarding their incidence and associated risk factors.

Hypothesis:
Epicardial pacemakers carry a risk for significant complications which is associated with patient and device characteristics.

Methods:
Retrospective study of all patients at a single center receiving an epicardial pacemaker at ≤12 months of age at time of implant. Patient characteristics: weight, length, BSA, reason for implantation, prematurity, congenital heart disease and concomitant surgery were obtained. Device characteristics: height, width, length, thickness, mass and volume were also obtained. Wilcoxon Rank-Sum and Fisher’s exact tests were used to compare patient and device characteristics with and without major complications (any re-admission after implant). Using identified characteristics associated with complication, pre-implantation cutoffs for high and low risk for complications were established.

Results:
Eighty-six patients were identified, age 73 d (IQR 13-166); 12 (14%) had a major complication, 7 (8%) needed surgical intervention (6 for wound dehiscence and 1 for pericardial effusion) and 3 (3%) required whole system explantation. Younger age (9 vs 89 d, p=0.01), lower weight (2.91 vs 4.44 kg, p=0.004) and lower BSA (0.19 vs 0.24 m
2
, p=0.03) were associated with major complications. Other patient characteristics were not statistically different. Device height, thickness, mass, volume and dual vs. single chamber system did not differ between groups; however device width differed in patients with complications (p=0.02). Based on these data, a cutoff of >3 kg and ≥ 6 days of age was established as lower risk. Patients with weight ≤ 3 kg and/or <6 days old had an OR of 18.1 (3.6-91.2, p<0.001) for developing a major complication. Using this model resulted in a sensitivity of 83% and positive and negative predictive values of 38% and 97%, respectively.

Conclusions:
Young age and low weight at the time of implant are risk factors for major complications while device characteristics appear to play a minor role. Using weight and age cutoffs of 3 kg and 6 days respectively may predict patients at very low risk for developing major complications.
Abstract 12169: LDL-C Levels and Treatment Patterns Among Adults With Heterozygous Familial Hypercholesterolemia in the United States: Data From the CASCADE-FH Registry
Authors: deGoma Emil M , Ahmad Zahid S , O'Brien Emily , Kindt Iris , Shrader Peter , Newman Connie B , Pokharel Yashashwi , Rader Daniel J , Moriarty Patrick M , Gidding Samuel S , Duell P. Barton , Shapiro Michael D , Linton MacRae F , Ballantyne Christie M , Duffy Danielle , Baum Seth J , Hemphill Linda C , Neal William A , Hudgins Lisa C , Ahmed Catherine D , Wilemon Katherine A , Row Matthew T , Knowles Joshua W
Published: July 2021

Introduction:
In the US, LDL-C levels and treatment patterns of patients with familial hypercholesterolemia (FH) – a group prioritized for statin therapy in the 2013 ACC/AHA cholesterol guidelines – remain poorly described. In 2013 the FH Foundation launched the CAscade SCreening for Awareness and DEtection (CASCADE) of FH Registry, the only active US FH patient registry addressing this knowledge gap.

Methods:
We conducted a 2-year (2013-2015) cross-sectional analysis among 1,295 adults with heterozygous FH enrolled in the CASCADE FH Registry from 10 US lipid clinics.

Results:
Mean (SD) age at enrollment was 54 (16) years; mean age at FH diagnosis was 45 (19) years; 59% were female; and 80% were white. Mean pretreatment and post-treatment LDL-C levels were 256 (66) and 156 (71) mg/dl, respectively. At enrollment, 43% of patients were taking high-intensity statin therapy; 25% were not taking a statin; and 45% received >1 LDL-lowering therapy. Among FH patients on LDL-lowering therapy, 25% achieved an LDL-C <100 mg/dl, and 41% achieved a ≥50% LDL-C reduction (Table). Factors associated with a ≥50% LDL-C reduction included high-intensity statin use (adjusted OR 2.24, 95% CI 1.47-3.42) and use of >1 LDL-lowering therapy (1.94, 1.29-2.93) (Figure). Atherosclerotic cardiovascular disease (ASCVD) was present in 37%, of whom 44% achieved a ≥50% LDL-C reduction and 9% achieved an LDL-C <70 mg/dl. Conclusions: Despite the high prevalence of ASCVD, several care gaps exist for FH patients enrolled in the CASCADE US registry: lack of early diagnosis, insufficient use of high-intensity statin therapy, and failure to achieve adequate LDL-C reductions.
Abstract 12205: Prediction of Heart Failure Symptoms Using Framingham and ARIC Scores in Patients With Non Ischemic Risk Factors at 1 Year Follow up
Authors: Yang Hong , Negishi Kazuaki , Nolan Mark , Wang Ying , Khan Faisal , Marwick Thomas
Published: July 2021

Background:
The Framingham heart failure score (FHS) and ARIC heart failure (HF) risk calculator are risk prediction tools that might facilitate the targeting of prevention strategies in pts with HF risk factors. We sought to compare their performance of predicting new HF symptoms in pts with risk factors.

Method:
Subjects ≥65 yo, with ≥ 1 HF risk (hypertension, type 2 diabetes, obesity, previous chemotherapy, family history of HF or previous cardiac history) were recruited from the local community. Absolute risk of incident HF risk was calculated using ARIC and FHS risk scores at baseline. Subjects underwent standard questionnaire, electrocardiogram, comprehensive echocardiogram and 6-minute walk (6MW) test. New HF based on Framingham criteria were assessed after a follow-up of 14±4 months.

Results:
Among 308 subjects (age 71±5 y; 50% men), median (IQR) 4 year risk of FHS and ARIC score were 4.0 (2-6.5) % and 6.2 (3.6-11.4) %, respectively. 19 participants developed new HF signs and symptoms (Framingham criteria). Compared with those remaining asymptomatic, those with new HF had higher ARIC score (p<0.001), more impaired GLS (p=0.036), larger left atrium volume (p=0.05) and left ventricular (LV) mass (p=0.049. They also had significant baseline 6MW test distance (p=0.003). There was no difference between their FHS score (p=0.325) and other conventional diastolic measures including LV ejection fraction, mitral E/A, e’ and E/e’ (p=0.108-0.804). AUC of ARIC and FHS were 0.74 (p=0.001) and 0.63 (p=0.057), respectively. The AUC of 6MW was 0.698 (p=0.005) (figure).

Conclusion:
The ARIC score appears to be more predictive than FHS score in prediction of new HF symptoms in non-ischemic stage A HF. 6MW test maybe used as an effective screening tool in community based process.
Abstract 12217: A Hierarchical Model for Stage B Heart Failure Screening- Results of a Classification and Regression-Based Decision Tree
Authors: Yang Hong , Negishi Kazuaki , Wang Ying , Nolan Mark , Marwick Thomas
Published: July 2021

Purpose:
In pts with stage A heart failure (SAHF), the identification of stage B HF relies on echo, but application of this to community based screening is limited by access and cost. We sought to use clinical characteristics and functional capacity to select at risk subjects for echo.

Methods:
308 asymptomatic subjects ≥65 years with the presence of ≥ 1 HF risk factor (hypertension, type 2 diabetes, obesity, previous chemotherapy, family history of heart failure and history of cardiac disease but not in HF) were recruited from the local community. All subjects underwent baseline risk quantification using ARIC risk score, functional assessment by 6 minute-walk test (6MW) and a comprehensive echocardiogram including conventional diastology and speckle tracking analysis for global longitudinal strain (GLS) and diastolic strain (DS). New HF was assessed at 14±4 m, based on 3 independent cardiologists using Framingham criteria. A classification and regression-based decision tree (CART) was built using baseline characteristics as independent variables.

Results:
In the CART model, a 3-level decision tree model was chosen to predict 19 pts (6%) who developed new HF at 1 year. The best predictor was 6MW followed by ARIC risk score (Figure). Using this model, 190 individuals (6MW≤330, or ARIC score>4.75%) were classified as high risk (9.5% events) and 118 (38%) were classified as low risk (0.8% events). GLS, DS and conventional diastolic measures (e’, E/e’) were significantly impaired in the high risk group (Figure). The AUC of the combined CART model with GLS was 0.72 (95% CI: 0.62-0.82, p=0.001) for new HF.

Conclusion:
Pts with SAHF with low HF risk and preserved exercise capacity have preserved LV function and a low event rate. GLS assessment in SAHF may be considered in pts with >4.75% 4 year risk, or 6MW≤330m.
Abstract 12286: Electrical Muscle Stimulation Improves Neurovascular Control and Exercise Tolerance in Hospitalised Advanced Heart Failure Patients
Authors: Groehs Raphaela V , Antunes-Correa Ligia M , Nobre Thais S , Alves Maria-Janieire N , Rondon Maria Urbana P , Pereira-Barretto Antônio Carlos , Negrao Carlos E
Published: July 2021

Introduction:
Advanced heart failure (HF) patients may stay for a long period of time in the hospital for the treatment of HF and prolonged inactivity causes complications that result in worsening of exercise tolerance. On the other hand, there is evidence that treatment with muscle low-frequency electrical stimulation (FES) provides important benefits for HF patients. This study investigated the effects of FES on neurovascular control and exercise tolerance in HF hospitalized patients.

Methods and results:
Thirty hospitalized patients for treatment of decompensated HF, functional class IV NYHA and ejection fraction ≤ 30% were consecutively randomised into two groups: 1) FES(n= 15; 54±2 years) and control(n= 15; 49±2 years). Muscle sympathetic nerve activity (MSNA) was directly recorded via microneurography and blood flow by venous occlusion plethysmography. Heart rate and blood pressure were evaluated on a beat-to-beat basis (Finometer). Exercise tolerance by six-minute walk test, quadriceps muscle strength by a dynamometer and quality of life by Minnesota Questionnaire. FES consisted of stimulating the lower limbs at 10 Hz frequency, 150 ms pulse width and 70 mA intensity for 60 min/day for 7 days/week for 10 consecutive days. The control group underwent electrical stimulation at intensity of 20 mA. Baseline characteristics were similar between groups, except age that was higher in FES group. FES significantly decreased MSNA burst frequency (49 ±5 vs. 35±5, P= 0.002) and burst incidence (61 ±6 vs. 49±7, P= 0.04). In addition, FES significantly increased leg blood flow (0.88 ±0.09 vs. 1.47 ±0.14, P<0.001) and muscle strength (13 ±1 to 21 ±2, P<0.001). No changes were found in control group. Walking distance (304 ±25 to 436 ±26, P<0.001 vs. 320 ±22 to 358 ±22, P= 0.001) and quality of life (69 ±5 to 26 ±3, P<0.001 vs. 70 ±3 to 45 ±3, P<0.001) improved in FES and control groups, respectively. However, these changes were greater in FES group.

Conclusion:
FES improves MSNA and vasoconstriction and increases exercise tolerance, muscle strength and quality of life in hospitalised HF patients. These findings support the use of FES as an adjuvant therapy for patients hospitalised to achieve the stabilisation of HF.
Abstract 12302: Mortality and Readmissions After Heart Failure Hospitalization in a Community Based Cohort: Estimating Risk Using the Acute Decompensated Heart Failure National Registry (ADHERE) Classification and Regression Tree (CART) Algorithm
Authors: Win Sithu , Hussain Imad , Hebl Virginia , Redfield Margaret M
Published: July 2021

Background:
The Acute Decompensated Heart Failure National Registry (ADHERE) Classification and Regression Tree (CART) algorithm is an accepted method to assess a heart failure (HF) patient’s risk of inpatient mortality based on the patient’s systolic blood pressure (≥115 vs. <115 mmHg), blood urea nitrogen (BUN; ≥43 vs. <43 mg/dL), and creatinine (≥2.75 vs. <2.75 mg/dL) at the time of admission. Whether the ADHERE CART algorithm identifies risk of longer term poor outcomes and is predictive in patients with systolic (EF < 50%) or diastolic (EF ≥ 50%) HF in the community is unclear.

Methods:
We identified all hospitalizations for a primary diagnosis of HF occurring between 2000-2013 in a community-based cohort living within 40 miles of Rochester, MN. Outcomes including length of stay, in-hospital mortality, 30 and 90 day post-discharge mortality and readmission for any cause at 30 and 90 days were compared across the ADHERE CART risk groups using logistic regression for the entire cohort and separately for systolic (EF < 50%) and diastolic (EF ≥ 50%) HF.

Results:
See Table. We examined 5,918 heart failure hospitalizations among 3,628 individual patients. Distribution of hospitalizations across the risk categories is shown in table. Length of stay, in-hospital mortality, 30 and 90 day mortality and 30 and 90 day readmission rates all increased with increasing ADHERE risk categories. Similar results were obtained separately for systolic and diastolic HF.

Conclusion:
The ADHERE CART algorithm is simple, uses data universally available on admission, and identifies groups that differ substantially in their post-discharge adverse outcomes regardless of HF type (systolic vs diastolic) in the community. The ADHERE CART algorithm may inform clinical decision regarding advanced HF treatments, end-of-life planning and care transition services in patients hospitalized for HF in the community.
Abstract 12354: Cardiac STAT3 Activation in Subacute Phase of Myocardial Infarction was Required for the Suppression of Adverse Cardiac Remodeling
Authors: Enomoto Daichi , Obana Masanori , Miyawaki Akimitsu , Mohri Tomomi , Maeda Makio , Sakata Yasushi , Nakayama Hiroyuki , Fujio Yasushi
Published: July 2021

Backgroud:
Cardiac STAT3 plays crucial roles in cardioprotection against acute injury after MI. However, mutated gp130-induced continuous STAT3 activation resulted in serious cardiac damage in the subacute phase of MI. Here, we examined the biological significance of intrinsic cardiac STAT3 during subacute/chronic phase of MI in a time specific manner using tamoxifen inducible cardiac specific STAT3 knockout mice (iCKO).

Methods and Results:
MI was generated by ligating the left coronary artery in mice. Immunoblotting revealed that STAT3 was rapidly activated in the myocardium, and that its activation was sustained to subacute phase after MI. To clarify the impact of cardiac STAT3 in subacute phase of MI,
STAT3
gene was ablated by administering tamoxifen to α-MHC-MerCreMer/STAT3
flox/flox
for 14 consecutive days from post-infarct day 11. As control mice, α-MHC-MerCreMer/STAT3
wild/wild
mice were used. Importantly, MI-induced cardiac STAT3 activation was significantly decreased in iCKO mice at day 24. Intriguingly, the mortality was accelerated in iCKO mice compared with control mice, coincident with increased heart weight/body weight. Masson’s trichrome staining demonstrated that cardiac STAT3 ablation resulted in severe fibrosis (iCKO; 58.3±6.7%, control; 40.8±9.3%,
p
<0.01, n=7 for control, n=8 for iCKO). Moreover, Echocardiography clarified that cardiac function was deteriorated in iCKO mice (FS: iCKO; 20.6±4.1%, control; 29.1±6.0%,
p
<0.05, n=10 for control, n=11 for iCKO). In border area, marked myocardial injuries, including ROS production and hypertrophy, were observed in iCKO mice. Finally, immunohistochemistry revealed that capillary density was decreased in iCKO mice (iCKO; 1724.2±119.4 capillaries/mm
2
, control; 2110.5±77.7 capillaries/mm
2
,
p
<0.01, n=30 fields from 5 mice for each).

Conclusions:
Cardiac STAT3 ablation in subacute phase of MI aggravated cardiac remodeling. The augmentation of STAT3 activity could be a therapeutic strategy for the prevention from the onset of chronic heart failure.
Abstract 12368: Impact of Weight Trends on Long-term Outcomes After Atrial Fibrillation Ablation in Obese Patients
Authors: Bunch T J , May Heidi T , Bair Tami L , Jacobs Victoria , Crandall Brian G , Cutler Michael , Weiss J P , Mallender Charles , Osborn Jeffrey S , Anderson Jeffrey L , Day John D
Published: July 2021

Introduction:
Catheter ablation of atrial fibrillation (AF) is an established therapeutic rhythm approach in symptomatic patients. Obesity is a dominant driver of AF recurrence after ablation. Weight reduction strategies lower general AF burden and as such may be critical to long-term success rates after ablation.

Hypothesis:
Long-term outcomes after AF ablation will be better in obese patients with sustained weight loss.

Methods:
All patients that underwent an index ablation with a BMI recorded and >30 kg/m
2
and at least 3 years of follow-up were included (n=407). The group was separated and compared by weight trends over the 3 years (1. Lost >3% of index weight, n=141; 2. Maintained index weight ±3%, n=147; 3. Gained >3% of index weight at 3 years, n=119). Long-term outcomes included AF recurrence and a composite defined as major adverse clinical events, MACE (stroke/TIA, heart failure (HF) hospitalization, and death).

Results:
The average age was 63.6±10.4 years, 59.3% were male and 51.7% had paroxysmal AF. AF comorbidities include: hypertension (79.5%), heart failure (36.0%), sleep apnea (35.2%), diabetes (28.9%), and stroke/TIA (5.9%). Those that maintained their weight (HR: 1.45, p=0.05) and those that gained weight (HR 1.54, p=0.07) were more likely to have AF recurrence compared to those that lost weight. Similarly, MACE increased from 18.4% in those that lost weight at 3 years compared to 18.6% (HR 1.32, p=0.29) in those that maintained their weight and 26.5% in those that gained weight (HR 2.01, p=0.02). A small group of patients (n=5), lost >3% then gained it back and ultimately increased their weight by 3%. This group had the highest rates of AF recurrence (100%).

Conclusion:
Maintained weight loss is a critical component in reducing AF recurrence rates after index catheter ablation in obese patients. Sustained weight loss also results in a reduction in AF-related comorbidities and mortality.
Abstract 12387: Comparison of Brain Injury and Quantitative Eeg Measures After Ventricular Fibrillation and Asphyxial Cardiac Arrest
Authors: Li Yongqin , Wang Pei , Chen Bihua , He Mi
Published: July 2021

Introduction:
Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest. However, different mechanisms of cardiac arrest cause different morphologic patterns of brain injury. In the present study, we compared postresuscitation brain injury and characteristics of EEG between animals resuscitated from cardiac arrest induced by ventricular fibrillation (VF) and asphyxiation (AS).

Methods:
Thirty-two healthy adult Sprague-Dawley rats of both sexes were randomized to either VF or AS. For animals assigned to VF, cardiac arrest was induced through high frequency transesophageal cardiac pacing and untreated for 5 mins. After 2 mins of cardiopulmonary resuscitation (CPR), a 2-J biphasic defibrillation shock was delivered. For AS, cardiac arrest was induced by airway obstruction, and CPR was initiated after pulselessness was maintained for 5 mins. Serum level of S100B were measured at baseline, 2 and 4 hrs postresuscitation. EEG were continuously measured for 4 hrs and was quantified by information quantity entropy (IQE).

Results:
There were no significant difference in body weight, baseline heart rate, mean arterial pressure and ejection fraction measurement. All of the animals were successfully resuscitated. However, duration of CPR (72±28 s vs. 200±59 s, p<0.001) was significantly shorter in AS group. Figure 1 shows the S100B (A) and IQE (B) measurement before and after resuscitation. Brain injuries were severe while EEG measures were lower in the AS group during the postresuscitation period. This was associated with considerably lower 96 hrs survival rate (25.0% vs. 87.5%, p<0.001) compared with VF.

Conclusion:
In this rat model, both VF and AS cardiac arrests caused brain injuries. Compared with VF, AS caused more severe brain injury and associated with lower survival rate. Quantitative EEG analysis was prognostic for neurological outcome when mechanisms of cardiac arrest was different.
Abstract 12432: Temporal Trends over a Decade of Defibrillator Therapy for Primary Prevention in Community Practice
Authors: Marijon Eloi , Providência Rui , Bouzeman Abdeslam , Algalarrondo Vincent , Narayanan Kumar , Defaye Pascal , Sadoul Nicolas , Piot Olivier , Klug Didier , Gras Daniel , Fauchier Laurent , Bordachar Pierre , Babuty Dominique , Deharo Jean-Claude , Leclercq Christophe , Boveda Serge ,   on Behalf of the DAI-PP Investigators
Published: July 2021

Aims:
Technology and clinical practice surrounding the use of the primary prevention implantable cardioverter defibrillator (ICD) are in a state of constant evolution. Using a multicenter national registry, we evaluated temporal trends in characteristics and outcomes over a decade of ICD therapy.

Methods and Results:
Between 2002-2012, 5,539 consecutive patients (age 62.5±11 years, 84.9% male, 60.2% with coronary artery disease) implanted with a primary prevention ICD from 12 centers in France were enrolled. Information on characteristics and outcomes (including causes of death) were evaluated over a median follow-up of 994 days [466-1,667]. In addition to a shift in the type of devices implanted with a significant increase in cardiac resynchronization therapy-defibrillator (CRT-D) over time (43.6 to 60.4%, P=0.0001), an increase in mean age (from 61.5±11.6 to 63.2±10.9 years, P=0.0016), proportion of non-ischemic cardiomyopathy (31.0 to 44.7%, P<0.0001) and women recipients (11.4 to 15.8%, P=0.004) was observed. A total of 1,181 patients (22.3%) received ≥1 appropriate therapy, inappropriate therapies occurred in 355 patients (6.7%) and 826 patients (15.2%) died mainly from cardiovascular cause (407 patients corresponding to 49.3%). Annual mortality incidence (5.4 to 4.3%, P=0.05) and annual incidence of appropriate therapy (10.4 to 7.1%, P=0.0004, Figure) significantly decreased over the decade. By contrast, incidences of ICD-related complications increased over the decade (4.6 to 7.6%, P=0.003).

Conclusion:
Our findings demonstrate significant changes in patterns of use and outcomes in primary prevention ICD over the last decade with reductions in mortality, appropriate therapies, associated with an increase in complications.