bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17156: No Major Change in Low-density Lipoprotein Cholesterol Goal Attainment in the United States From 2003 to 2012: A Time-sensitivity Analysis Using National Health and Nutrition Examination Survey Data
Authors: Toth Peter P , Palmer Michael K , Henriksson Karin M
Published: July 2021

Introduction:
Although use of lipid-lowering therapies (LLT) for treatment of dyslipidemia is increasing, there is little evidence that this has increased the percentage of patients achieving LDL-C goals of <100 mg/dL, <130 mg/dL, and <160 mg/dL for adults at high, intermediate, and low CHD risk, respectively (based on NCEP ATP III). We used reported LDL-C levels in the National Health and Nutrition Examination Survey (NHANES) to estimate proportion of the US adult population meeting LDL-C goals as a function of time (2003-2012).

Methods:
Coronary heart disease risk using NCEP ATP III criteria was assessed in adult participants in 2-yearly NHANES surveys from 2003-2004 to 2011-2012. The proportion of each risk group meeting LDL-C goals and the proportion receiving LLT were calculated.

Results:
Estimates for the US population were based on 11,256 observations from NHANES (2003-2012). No obvious change over time was observed in the distribution of risk, with 66%, 17%, and 17% of the population estimated to be at low, intermediate and high risk in 2003-2004 and 67%, 14%, and 19%, respectively, in 2011-2012. From 2003-2012, a statistically significant increase in the use of LLT was observed in low- (p<0.0001) and high-risk (p=0.008) groups (Figure). Although there was an increase in proportion of patients in the intermediate- and high-risk categories achieving LDL-C goals between 2003-2004 and 2005-2006, there was no significant improvement in LDL-C goal attainment in low- (p=0.89), intermediate- (p=0.41) or high-risk (p=0.09) groups over the entire period (Figure).

Conclusion:
Despite increased use of LLT, we observed no trend for improvement in LDL-C goal attainment in adults in the US population. Approximately 69 million adults (33% of the population) are at high or intermediate CHD risk, and many are not at their LDL-C goal, highlighting the need for more aggressive identification and treatment of patients at risk, objectives articulated by the ACC/AHA guideline.
Abstract 17184: Achievement Of LDL-cholesterol Reduction Targets is Associated With Reduced Cardiovascular Disease Risk Among Patients With Familial Hypercholesterolemia in a Large Electronic Medical Record Database
Authors: Cohen Sarah S , Kabagambe Edmond K , Shirey-Rice Jana , Hardin Jill , Monda Keri , Fryzek Jon P , Fazio Sergio , Denny Joshua C , Wei Wei-Qi , Lipworth Loren
Published: July 2021

Introduction:
Heterozygous familial hypercholesterolemia (FH) is common but under-recognized, with an estimated prevalence of 1:200-1:500 and an associated high risk of premature cardiovascular disease (CVD). Little is known regarding the association between change in low-density lipoprotein cholesterol (LDL-C) and long-term CVD risk in FH patients. We hypothesized that FH patients who achieved LDL-C
<
100 mg/dL or reduction ≥50% post-statin initiation would have reduced risk of non-fatal myocardial infarction (MI) or revascularization.

Methods:
Using Dutch Lipid Network criteria components, 174 “probable” and 125 “definite” FH patients with LDL-C measurements available before and after statin initiation were identified in the Vanderbilt de-identified electronic medical records (EMR) Synthetic Derivative database, 1996-2014. First non-fatal MI or revascularization was identified via validated EMR algorithm with positive predictive value=92%. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained from Cox regression models in relation to LDL-C levels (≥ vs. <50% reduction or
<
vs. >100 mg/dL post-statin), adjusted for age, race, sex, blood pressure, smoking, and body mass index.

Results:
Mean (+/- SD) LDL-C levels prior to initiation of statin therapy were 207 (+/- 31) for probable and 304 (+/- 124) mg/dL for definite FH patients. Similar proportions of patients attained ≥50% reduction in LDL-C after statin initiation in both groups (24.1% and 26.4%), while 22.4% achieved LDL-C
<
100 mg/dL in the probable group compared to only 4.8% in the definite group. Over median follow-up of 5.4 years, 34 probable and 19 definite FH patients experienced non-fatal MI or revascularization. The HR (95% CI) among those with post-statin LDL-C
<
100 vs >100 mg/dL was 0.59 (0.23-1.52) overall, with no evidence of effect modification by probable/definite FH status (likelihood ratio test (LRT) p-value=0.58). A similar pattern was observed for LDL-C change ≥50% vs <50% (HR (95% CI) 0.58 (0.24-1.38), LRT p-value=0.44).

Conclusions:
In this small sample of FH patients, lowering LDL-C to <100 mg/dL suggests a reduction in CVD risk, but few attained this LDL-C target. These results warrant further research in larger populations of this understudied condition.
Abstract 17188: Calcific Degenerative Mitral Disease vs Myxomatous Degeneration: Crystallizing the Differences
Authors: Lawrie Gerald M , Earle Nan R , Earle Elizabeth A
Published: July 2021

Introduction:
Myxomatous (M) and other non-M, non-ischemic valve pathologies are often all classified as “degenerative mitral valve disease.” We have seen at TEE and surgery a subgroup of older patients with normal or reduced leaflet area, leaflet cholesterol deposition, annular fibrosis and calcification and thickened chordae - at most only two are ruptured. We classify these pts as “calcific degenerative (D).”

Hypothesis:
Pts with D have different outcomes and require different techniques than pts with M.

Methods:
Since 1994, D and M have been recorded prospectively and separately; 205 patients had D pathology, 654 had M.

Results:
D pts were more often female: 63% (130/205) vs. M, 32% (209/654) p<0.0001; older : 69.20±11.34 vs. 60.86±13.42 years, p<0.0001; had a lower preop EF: 55.97±12.82 vs. 61.80±9.10, p<0.0001; smaller preop annular AP diameter: 41.59±5.60 vs. 44.36±4.00, p<0.0001; more concurrent AVRs: 8.8% (18/205) vs. M: 3.5% (23/654) p=0.0038; had fewer posterior chordal replacements: 4.06±1.54 vs. 4.67±1.53, p=0.0016 and smaller ring sizes D: 28.22±3.06 vs. M: 30.72±2.86, p<0.0001. Periop mortality was higher in D: 3.9% (8/205) in D vs 1.2% (8/654) of M pts, p=0.0293. Late 10-yr survival (Kaplan-Meier) was D, 37.94%, and for M, 71.3%, p<0.0001. Late 10-yr freedom from reoperation (Kaplan-Meier) was for D, 95.6% and for M, 93.2%, p=0.375. Late 10-yr freedom from significant mitral regurgitation (MR) (Kaplan-Meier) was for D, 79.9%, and for M, 85.9%, p=0.269. Cox regression for predictors of mortality identified age (relative risk (RR) 1.078, p<0.0001), sex (RR 0.715, p=0.0320) preop EF (RR 0.985, p=0.0220), concomitant CAB (RR 1.614, p=0.0058), posterior leaflet repaired (RR 0.581, p=0.0058) or both posterior and anterior leaflet repaired (RR 0.500, p=0.0150), and leaflet calcification, (RR 1.734, p=0.0440); for predictors of reoperation, age (RR 0.971, p=0.048) and sex (RR 2.914, p=0.040); and for a predictor of late MR, annuloplasty ring size (RR 1.242, p=0.0094).

Conclusions:
These data confirmed that the D group had distinct clinical and pathological features which can be identified preoperatively and intraoperatively. Leaflet resection is not successful in these patients. Reconstructive techniques are preferred.
Abstract 17214: Differential Relationships Between Serum Cholesterol Efflux Capacities Measured From Three Cell Models and Coronary Artery Disease Status in the Montreal Heart Institute Biobank
Authors: Rhainds David , Cecile Low-Kam , Marie Boulé , Sonia Alem , Ian Mongrain , Marie-Pierre Dubé , Guillaume Lettre , Jean-Claude Tardif
Published: July 2021

Recent clinical trials and Mendelian randomization studies suggest that raising HDL-cholesterol (HDL-C) concentration by itself is insufficient to lower cardiovascular (CV) risk, despite the established inverse relationship between HDL-C and cardiovascular risk. CV protection may derive from other characteristics of HDL. Such characteristics include the cholesterol efflux capacity of serum, the process by which HDL particles accept cholesterol from macrophages and other cell types. Recently, higher cholesterol efflux capacity was inversely associated with incident CV events over a >9 year period of follow-up, with a 67% risk reduction in the highest quartile of efflux. In our study, cholesterol efflux capacity was measured for 2000 patients from the Montreal Heart Institute Biobank as the ratio of pooled control serum. When comparing unadjusted cholesterol efflux values between 1000 controls and 1000 cases with previous myocardial infarction (MI), we observed significant decreases of efflux capacity in cases with J774 macrophages in basal and cAMP-stimulated conditions, with human HepG2 hepatocytes and with BHK cells expressing human ABCA1. In regression models of MI status against efflux variables, also adjusted for age, sex, HDL-C, triglycerides and statin use, the reduction in cholesterol efflux capacity in cases vs. controls remained highly significant for J774 cells in basal (p value = 5.8x10-11) and cAMP-stimulated conditions (p = 5.3x10-8), while the difference was lost with HepG2 cells (p=0.16) and was reversed for ABCA1-dependent efflux using BHK-ABCA1 cells (p=5.9x10-4). Thus, the relationship of cholesterol efflux capacity of serum HDL and cardiovascular status is heterogeneous, which suggest that the repertoire of cholesterol transporters expressed in cells and samples characteristics, such as the HDL proteome and lipidome, interact in a unique manner for each cell type. Future work will consist in identifying sources of such differences at the molecular level.
Abstract 17263: Cardiac Myosin Binding Protein-C Phosphorylation Mitigates Pressure-Overload Heart Failure Despite Alterations in Calcium Handling
Authors: Liu Yang , Rosas Paola C , Abdalla Mohamed I , Duonge Kevin W , Kidwell David T , Dusio Giuseppina F , Tong Carl W
Published: July 2021

Heart failure with reduced ejection (HFrEF) fraction exhibits both systolic and diastolic dysfunctions; therefore, treatments that improve contractility and lusitropy will be helpful. Cardiac myosin binding protein-C (cMyBP-C), which is a thick filament protein, can increase rate of cross-bridge cycling by its phosphorylation status to enhance contractility and lusitropy. Consequently, we hypothesized that cMyBP-C phosphorylation mitigates HFrEF by preserving systolic and diastolic functions. We tested our idea by challenging WT cMyBP-C(tWT), phosphorylation-deficient cMyBP-C(t3SA):S273A/S282A/S302A, and phosphorylation-mimetic cMyBP-C(t3SD):S273D/S282D/S302D mouse models with trans-aortic constriction (TAC) to induce pressure-overload HFrEF. Survival at 5 weeks showed notable differences (tWT 75.6±6.7% n=41, t3SA 53.4±6.7% n=68, t3SD 92.1±4.4% n=38, p=0.00037). Serial echocardiography showed that cardiac structure and function deteriorated for all mouse models. In comparison to tWT at post-TAC week-5, t3SA demonstrated ventricular dilation and reduced ejection fraction (EF); conversely, t3SD exhibited better preservation of diastolic function (smaller E/Ea, where E=blood flow Doppler and Ea=tissue Doppler of peak myocardial relaxation velocity). Electrically paced intact papillary muscles from t3SA and t3SD demonstrated slower intracellular calcium decay (smaller decay rate constant kCa). Western blotting showed: (1) decreased calcium-ATPase (SERCA2a) expression in t3SA and t3SD, (2) lowest ryanodine receptor (RyR2) expression in t3SD, and (3) decreased calcium calmodulin kinase-2 phosphorylation (pCaMK2) only in t3SD. These calcium handling protein alterations likely prevented stronger rescue by cMyBP-C phosphorylation mimetic. Thus, cMyBP-C phosphorylation mimetic mitigated TAC-induced HFrEF (better survival and preservation of diastolic function) despite depression of calcium handling proteins.
Abstract 17380: End-tidal Carbon Dioxide During Resuscitation is Associated With CPR Depth and Ventilatory Rate
Authors: Tonna Joseph , Clark Cabe R , Fogg Benjamin R , Youngquist Scott
Published: July 2021

Introduction:
End-tidal carbon dioxide (ETCO2) has been proposed as a physiologic marker of blood flow during CPR.

Hypothesis:
We hypothesized that ETCO2 values would be associated with initial rhythm, witnessed status, impedance threshold device (ITD) use, CPR quality measures and ventilatory rates (VR).

Methods:
Chest compression (CC) metrics, VR, and ETCO2 values from prehospital resuscitation attempts were averaged over each 1 min of resuscitation. When return of spontaneous circulation (ROSC) was identified, as evidenced by the cessation of CC and measurement of a blood pressure, we censored 1 min prior to the termination of CC to reduce the measurement of unrecognized ROSC physiology. Mixed effects models were used for analysis.

Results:
Monitor data from N=102 adult prehospital resuscitation attempts was available for analysis, providing 1,079 (1-min) epochs for analysis (median of 8 min/case, IQR 4-14). ETCO2 appeared at a median of 9 min (IQR 6-12) into resuscitation, measured from an endotracheal tube (78%), laryngeal tube (21%), and bag valve mask (1%). Median VR was 9 breaths/min (IQR 6-11). Average initial ETCO2 was 28 (95% CI 25-31) followed by an average rise of 0.8 mm Hg/min (95% CI 0.5-1.1), regardless of ITD use, initial rhythm, or witnessed status. In univariate analysis, ETCO2 was not associated with CC fraction, rate, or release velocity but was associated with CC depth (2.7 mm Hg/inch of depth, 95% CI 0.1-5.4), and VR (quadratic response, p<0.0001). Results held in multivariate analysis. In the narrow range of low VRs observed in our sample, increased VRs were associated with higher ETCO2 values between 0-17 breaths/min before falling at higher rates (FIGURE).

Conclusions:
Similar to others, we observed a linear association between ETCO2 and CC depth but a quadratic relationship between ETCO2 and VR during prehospital resuscitation. Improving CC depth and maintaining a VR of 10 breaths/min may optimize ETCO2 values in adults.
Abstract 17428: Impact of Asymptomatic Cerebral Microbleeds or Lacunar Infarction on Clinical Outcome in Patients With Coronary Artery Disease (CAD) Requiring Percutaneous Coronary Intervention
Authors: Hokimoto Seiji , Tabata Noriaki , Akasaka Tomonori , Sakamoto Kenji , Tsujita Kenichi , Yamamoto Eiichiro , Yamamuro Megumi , Sueta Daisuke , Kaikita Koichi , Kojima Sunao , Ogawa Hisao
Published: July 2021

Background:
Patients with coronary artery disease (CAD) are often complicated with cerebrovascular disease (CVD). Although there are many reports on the relation between stoke with symptomatic signs and CAD, there are few studies on cerebral microbleeds or lacunar infarction without symptomatic signs. The aim was to examine the prevalence of cerebral microbleeds or lacunar infarction without symptoms and clinical outcome in CAD patients.

Methods:
Among 1,091 consecutive CAD patients who required percutaneous coronary intervention (PCI), patients with non-lacunar infarction more severe than lacunar infarction or old cerebral hemorrhage by computed tomography (CT) or magnetic resonance imaging (MRI) were excluded. We analyzed CAD patients with cerebral microbleeds or lacunar infarction without overt neurological signs (ML group; n=98, 71males) compared with patients without cerebral findings of CT or MRI and stroke history as control (N group; n=762, 525males). Clinical endpoints were cardiovascular death, myocardial infarction (MI), stroke, unstable angina and urgent revascularization.

Results:
ML group had a high age (72.9±9.6 vs. 69.2±10.8ys; P=0.001), high incidence of diabetes mellitus (58.2 vs. 47.2%; P=0.042), peripheral artery disease (21.4 vs. 11.5%; P=0.005), and renal dysfunction (49.0 vs. 37.3%; P=0.025), and high levels of fibrinogen (435 vs. 402mg/dl; P=0.005), and high brachial-ankle pulse wave velocity (1975 vs. 1786cm/sec; P=0.001) compared with N group. Cardiovascular event rate was significantly higher in ML group than in N group (11.2 vs. 4.7%, P=0.008). Details in clinical outcome were as follows: cardiovascular death (ML group vs. N group, 0 vs. 0.9%; P=0.341), MI (1.0 vs. 0.5%; P=0.544), stroke (4.1 vs.0.7%; P=0.002), unstable angina (5.1 vs. 2.5%; P=0.140), revascularization (2.0 vs. 0.7%; P=0.498), respectively. Multiple regression analysis identified findings of microbleeds or lacunar infarction as a predictor of clinical events (OR, 2.830; 95%CI, 1.328-6.031; P=0.007).

Conclusions:
There was high incidence of brain MRI or CT findings without symptom in CAD patients. We should pay attention to the asymptomatic patients with microbleeds or lacunar infarction irrespective of overt previous stroke.
Abstract 17461: Clinical Significance of No Pulmonary Vein Potential at Redo-procedure After Catheter Ablation for Atrial Fibrillation
Authors: Kim Tae-Hoon , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam
Published: July 2021

Introduction:
Long-lasting pulmonary vein isolation (PVI) has been shown to be the key determinants for clinical outcome in both patients with paroxysmal and persistent atrial fibrillation (AF).

Hypothesis:
Although reconnected PV potential (PVP) has been regarded as a main mechanism of AF recurrence after catheter ablation, PVIs are well preserved in some patients at redo-procedure after recurrence. Therefore, we explored the characteristics and clinical outcome of the patients with negative PVP at redo-procedure.

Methods:
Among 1522 patients with AF who underwent catheter ablation, 143 patients (79.0% male, 56.1±10.0 years old, 65.0% paroxysmal AF) refractory to antiarrhythmic drug underwent redo-procedure. PVP was not shown in 52 patients (PVP- group, 36.4%), but remaining 91 patients showed PVP (PVP+ group, 234/364 (64.3%) of PVs). We mapped triggers with isoproterenol infusion in both groups (after PVI in PVP+ group). Depending on mapping finding, we ablated non-PV foci and added linear ablation or complex fractionated atrial electrogram (CFAE)-guided ablation.

Results:
1. PVP- group was independently associated with female gender (OR 2.64 95%CI 1.13~6.21, p=0.026) and later de novo clinical recurrence timing (OR 1.02 95% CI 1.00~1.04, p=0.047). 2. Additional linear ablations were more likely to be performed in PVP- group (92.2% vs. 61.5%, p<0.001), but total ablation time (2411.3±1082.8 vs. 3144.8 ± 1412.5 sec, p=0.003) and procedure time (164.2± 51.4 vs. 144.2±47.1 min, p=0.027) were shorter in PVP- group than in PVP+ group. 3. During 18.4±10.2 months follow-up after redo-ablation, PVP- group showed significantly higher clinical recurrence rate than PVP+ group regardless of redo-ablation strategies (Kaplan Meier, Log Rank p=0.011). The presence of recurred PV connection (PVP+) was independently associated with lower recurrence of AF after repeat ablation (HR 0.46, 95% CI 0.21 - 0.98, p=0.043).

Conclusions:
AF patients with well-preserved PVI recurred later timing after de novo ablation, but showed poor clinical outcome after redo-ablation procedure, suggesting a potential AF progression.
Abstract 17473: Obesity is Associated With Impaired Left Atrial Function in Young Patients With Recent Onset Atrial Fibrillation
Authors: Oemrawsingh Dinant N , Vermond Rob A , Marcos Ernaldo G , Hobbelt Anne H , Hummel Yoran M , van Melle Joost P , Blaauw Yuri , van Gelder Isabelle C , Rienstra Michiel
Published: July 2021

Introduction:
Obesity is a risk factor for atrial fibrillation (AF), and reduction of weight has been shown to reduce the burden of AF. However, the exact underlying pathogenesis is unknown.

Hypothesis:
We hypothesize that obesity is related with impaired left atrial function, measured with echocardiographic strain analysis, in young patients (<60 years) with recent onset AF (AF history< 3 years).

Methods:
We studied 94 patients of the Phenotyping young-onset AF patients study, all with sinus rhythm during echocardiography. Detailed clinical and echocardiographic information was collected. Three strain-patterns (reservoir, activation, and conduit strain) representing left atrial functional phases were measured.

Results:
Of the 94 patients, 32 were obese and 62 were non-obese (34±3 kg/m2 vs. 25±2 kg/m2, p<0.001). Mean age was 50±9 years and 34% were women. No significant differences in cardiovascular conditions and risk factors were found, except for diabetes mellitus (13% vs. 2%, p=0.026), and metabolic syndrome (56% vs. 8%, p<0.001), both more common in obese patients. Left atrial volume index (mean 30±8ml/m2), and left ventricular mass index and ejection fraction were not significantly different between both groups. However, the left atrial reservoir (27±8 vs. 33±10%, p=0.008) and conduit strain (16±6 vs. 20±8%, p=0.011) were significantly reduced in obese patients, the left atrial activation strain was not (p=0.118). Using linear regression analysis adjusting for significant baseline differences, the association between reservoir strain (beta=-0.304, p=0.013), and conduit strain (beta=-0.246, p=0.045) and obesity remained significant. The correlation between BMI and left atrial function are shown in the figure.

Conclusions:
In young patients with recent onset AF, obesity is associated with impaired left atrial function, in absence of dilatation. Left atrial dysfunction may be the first sign of atrial remodeling in obese AF patients.
Abstract 17583: Autophagy Protects the Heart Against Pressure Overload Induced Heart Failure
Authors: Shirakabe Akihiro , Ikeda Yoshiyuki , Zai Peiyong , Saito Toshiro , Sadoshima Junichi
Published: July 2021

Autophagy is an important mechanism for the degradation of cytosolic proteins and organelles. We investigated how autophagy is regulated in the heart in response to pressure overload (PO). Mice were subjected to transverse aortic constriction (TAC) for multiple durations ranging from 1 hour to 30 days. Left ventricular (LV) weight/tibial length (TL) was significantly elevated at Day 5 (6.21 ± 0.10 vs 4.59 ± 0.10, p<0.05) and thereafter. Ejection fraction (EF) was maintained at Day 7 (82.1±3.4 vs 78.4±3.2%), but gradually decreased thereafter (at Day 30, 51.0±4.5, p<0.05). The level of LC3II increased rapidly, peaking at 3 hours (2.4 fold, p<0.05), returned to normal by 24 hours, and then was significantly decreased at Day 5 (-40.0%, p<0.05) and thereafter. Autophagic flux was evaluated with tandem fluorescent LC3. At 6 hours, both GFP/RFP double positive (yellow) dots and RFP dots were significantly increased in the TAC group compared to the sham group, with or without chloroquine (CQ) (yellow 12±2 vs 4±0 CQ(-), 23±3 vs 9±1 CQ(+); RFP 13±2 vs 5±1 CQ(-), 19±1 vs 13±1 CQ(+)). However, both yellow and RFP dots were significantly decreased at Day 7 and thereafter in the TAC group compared to the sham group, with or without CQ. These data suggest that autophagic flux is activated only transiently after TAC, but is inactivated after Day 5. To examine the functional significance of autophagy during PO, beclin1 heterozygous knockout (beclin1-hetKO) mice, atg7 cardiac-specific knockout (Atg7-CKO) mice, and cardiac-specific U6-shRNA beclin1 (U6shRNAbeclin1) mice were subjected to TAC. At Day 7 and 14 of TAC, decreases in EF (60.7 ± 4.8%, 53.8 ± 2.1% and 46.7 ± 5.9%, p<0.05) and increases in lung weight/TL (8.43 ± 0.87, 11.04 ± 4.16 and 18.76 ± 3.77, p<0.05) were exacerbated in beclin1-hetKO, atg7-CKO and U6shRNAbeclin1 mice compared to in control mice. These results suggest that, after transient activation during the initial 24 hours, PO inhibits autophagy below control levels after Day 5, which coincides with the development of cardiac dysfunction. Since heart failure is exacerbated by further suppression of autophagy, autophagy during PO protects the heart from cardiac dysfunction and PO-induced downregulation of autophagy exacerbates heart failure.
Abstract 17635: Can Published Reference Values Predict Patient-prosthesis Mismatch?
Authors: Bansal Prerna , Abudiab Muaz , Chaliki Kalyan , Punnaiah Marella , Chaliki Hari
Published: July 2021

Background:
Patient-prosthesis mismatch (PPM) is still a frequently encountered problem after aortic valve surgery for aortic stenosis(AS). Advanced planning for prevention of PPM would be beneficial. We hypothesized that identification of severe PPM based on chosen surgical valve will predict development of severe PPM after surgery.

Methods:
Fifty one patients (74±13yrs) with severe aortic valve stenosis who underwent aortic valve surgery had postoperative echocardiogram (TTE) within 6 months. Severe PPM was defined as effective orifice area index (EOAI)<0.65 cm2/m2.We calculated predicted severe PPM using published references values of the prosthetic valve. We used mean value and the values one standard deviation above and below. We compared these values to the actual PPM based on postoperative TTE.

Results:
All patients had severe AS (MG50±7 mm Hg) and an LV EF of 56±15%. Forty four patients had tissue valves implanted and 7 had mechanical valves implanted. Mean time between postoperative TTE and surgery was 39± 60 days. When the mean reference values for the valve implanted was used, only 1 patient (2%) was predicted to have severe PPM. However, based on postoperative TTE, 6 patients (13%) had severe PPM. There was no correlation between EOAI based on postop TTE and mean published reference values (Figure).When the EOAI below one SD of the published reference value was chosen, the predicted incidence of severe PPM was 38%. When the EOAI above one SD was chosen for the reference value none of the patients were predicted to have PPM. Sensitivity and specificity to identify severe PPM was 17% and 100% for mean published reference value while it was 0% and 100% for +1 SD and 83% and 68% for -1 SD.

Conclusions:
1) Use of mean published reference values markedly under estimate the true incidence of post-operative PPM and has unacceptably low sensitivity. 2) Predicted occurrence of PPM was widely variable (0% to 38%) based on the published reference values. Larger studies are needed.
Abstract 17732: Pulseless Electrical Activity in Middle Age: Is There a Connection to Obesity?
Authors: Teodorescu Carmen , Reinier Kyndaron , Uy-Evanado Audrey , Mariani Ronald , Gunson Karen , Jui Jonathan , Chugh Sumeet S
Published: July 2021

Introduction:
Sudden cardiac arrest (SCA) presenting with pulseless electrical activity (PEA) has a significantly higher mortality than ventricular fibrillation/tachycardia (VF/VT). Due to the lack of data in middle aged SCA cases, we evaluated predictors of PEA in in this age group.

Methods:
Out-of-hospital SCA cases were identified from a large ongoing population-based study in a Northwest US metro area (population approx. 1 million), and confirmed by a process of in-house adjudication. Presenting rhythms were identified from review of first responder reports and electrocardiographic recordings. Pearson’s x2 test and independent samples t-test were used for univariate comparisons of middle-aged (35.0-59.9 years) vs. older adults among PEA and VF/VT groups. Logistic regression was used to evaluate significant factors associated with middle-aged vs. older group.

Results:
A total of 151 middle-aged and 398 older adults presented with PEA. Middle-aged cases were more likely to be male (72.9% vs. 56.0%, p=0.0003), of African American race (14.1% vs. 7.5%, p=0.008), arrest in public locations (22.5% vs. 9.3%, p=0.0004), be unwitnessed (34.4% vs. 23.7%, p=0.02) and have higher survival to hospital discharge (9.3% vs. 4.8%, p=0.05). There was no difference in the response time and bystander CPR (p≥0.11). Middle-aged PEA cases had a lower comorbidity index compared to older PEA (p<0.0001). Obesity was significantly more common among middle-aged compared to older adults in the PEA group (49.0% vs. 35.5%, p=0.02) and remained a significant determinant after multivariable adjustment [OR 1.91 (95% CI 1.14-3.19, p=0.01)]. Among the VF/VT group, the demographic and resuscitation characteristics followed a similar pattern between middle-aged vs. older adults as in the PEA group. However, in the VF/VT group there was no significant difference in the obesity prevalence (p=0.10).

Conclusion:
Middle-aged cases presenting with PEA were independently associated with obesity. Given the current epidemic of obesity, these findings have significant public health implications and warrant further detailed investigation.
Abstract 17788: Repaired Coarctation is Associated With Central Hypertension, Increased Vessel Stiffness and Abnormal Wave Reflections - A Novel CMR Hemodynamics Study
Authors: Quail Michael A , Short Rebekah , Pandya Bejal , Steeden Jennifer A , Khushnood Abbas , Segers Patrick , Muthurangu Vivek
Published: July 2021

Introduction:
The basis of late cardiovascular mortality following coarctation repair is poorly understood. Although hypertension has been implicated, peripheral systolic pressure (pSBP) has not been shown to be definitively higher in this group. This may be because mortality is more related to central systolic pressure (cSBP) than pSBP. We have developed a novel cardiovascular magnetic resonance (CMR) protocol that allows assessment of cSBP and it components: resistance, compliance and wave reflections. The main aims of this study were i) characterize hemodynamic differences between patients and controls ii) define hemodynamic determinants of cSBP in patients and iii) Identify possible biomarkers amongst covariates associated with LV mass (LVM).

Methods:
75 subjects, 50 patients with repaired coarctation, median age 23.5yrs (74% male) and 25 matched controls; 21.0yrs (72% male) were recruited. Ascending aorta area and flow waveforms were obtained using a high temporal resolution (10ms) spiral phase-contrast MR flow sequence. This data was used to derive cSBP and perform wave intensity analysis (WIA) non-invasively using previously validated techniques. The determinants of cSBP and LVM were assessed using multivariable linear regression analysis.

Results:
Central SBP was significantly higher in patients compared to controls (115±13 vs 107±9mmHg [mean±sd], p=0.002). However, there was only a trend towards higher pSBP (123±15 vs 117±11mmHg, p=0.052). Patients had reduced arterial compliance, increased characteristic impedance and larger backward compression waves (BCW) than controls; and these parameters were independently associated with cSBP. LVM index was significantly higher in patients than controls (73.1±14.6 vs 58.9±9.7g/m
2
, p=0.0001). Independent predictors of LVM included cSBP (p=0.001) and BCW (p=0.002), but importantly not pSBP or coarctation index.

Conclusions:
Non-invasive assessment of fundamental arterial hemodynamics by CMR is feasible. Using these techniques we have shown elevated cSBP in patients after coarctation repair. Elevated cSBP and BCW are important determinants of increased LVM following coarctation repair. These metrics represent superior biomarkers of afterload than coarctation index and pSBP.
Abstract 17846: Prognosis of High Sinus Heart Rate After Catheter Ablation for Atrial Fibrillation
Authors: Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Kim Jong-Youn , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam
Published: July 2021

Introduction:
Although radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) increases a sinus heart rate (HR) after rhythm control, its mechanism and prognosis have not yet been clearly elucidated.

Hypothesis:
We hypothesized that post-procedural high sinus HR is associated with better clinical outcome of AF ablation without hemodynamic adverse effects.

Methods:
We included 991 AF patients (75% male, 58 ± 11 years old, 70% paroxysmal AF [PAF]) who had analyzable HR variability (HRV) at 3-months and 1-year after RFCA, and pre- and post-1-year echocardiogram. Average HR measured by 24-hour Holter greater than 2SD (≥92bpm) was defined as post-ablation high sinus HR.

Results:
1. Average heart rate was increased significantly (68.8±13.1 to 71.4±10.7bpm, p<0.001), and high sinus HR (≥92bpm) was observed in 28 patients (2.8%) at 3-months after AF ablation. All of them tolerated well, 21% (6/28) were taking low dose β-blocker, and 36% (10/28) kept average HR≥92bpm at 1-year after RFCA. 2. High sinus HR was independently associated with pre-procedural high average HR (OR 1.097; 95% CI 1.029 to 1.169, p=0.005), high left atrial (LA) voltage (OR 3.545; 95% CI 1.183 to 10.618, p=0.024), and reduced rMSSD at 3-months HRV (OR 0.959; 95% CI 0.919 to 0.999, p=0.047). 3. At 1-year follow-up echocardiogram, LA reverse remodeling (ΔLA; -1.1±3.7 vs. -3.0±4.6mm, p=0.055) and the improvement of ejection fraction (ΔEF; 0.7±8.4 vs. 1.7±7.7%, p=0.529) were not significantly different between the patients with high sinus HR and those without. 4. During 27±17 months of follow-up, the patients with high sinus HR at 3-months after RFCA showed significantly lower clinical recurrence than those without (log rank, p=0.020).

Conclusions:
High sinus HR 3-months after AF ablation is observed in patients with less remodeled LA with significant post-procedure vagal modulation. High sinus HR after AF ablation did not show hemodynamic adverse effect and was associated with lower clinical recurrence rate of AF after RFCA.
Abstract 17904: Deficiency of Yes-associated Protein Promotes Cardiac Dysfunction in Response to Pressure Overload in the Mouse Heart
Authors: Byun Jaemin , Del Re Dominic P , Zhai Peiyong , Shirakabe Akihiro , Sadoshima Junichi
Published: July 2021

Yes-Associated Protein (YAP), a downstream effector of the Hippo pathway, plays an important role in regulating cell proliferation and survival in mammalian cells. We have shown that cardiac-specific loss of YAP leads to increased cardiomyocyte (CM) apoptosis and impaired hypertrophy during chronic myocardial infarction in the mouse heart. However, it remains unclear whether YAP mediates hypertrophy of individual CMs under stress conditions in vivo. We hypothesized that endogenous YAP plays an essential role in mediating hypertrophy and survival of CMs in response to pressure overload (PO).

Three-month-old YAP+/fl;α-MHC-Cre (YAP-cKO) and YAP+/fl (control) mice were subjected to transverse aortic constriction (TAC). Two weeks later, YAP-cKO and control mice developed similar levels of cardiac hypertrophy (left ventricular (LV) weight/tibia length: 7.27±0.38, 6.93±0.29) compared to sham (5.08±0.14, 4.07±0.33). LV CM cross sectional area was similarly increased by TAC in YAP-cKO and control mice compared to their respective shams. Induction of fetal-type genes, such as Anf and Myh7, was also similar in YAP-cKO and control mice. YAP-cKO and control mice exhibited similar baseline LV systolic function (ejection fraction (EF): 75, 76%). YAP-cKO mice had significantly decreased LV function after TAC compared to Sham-control mice (EF: 51%, 76%, p<0.05) and TAC-control mice (75%, p<0.05). LV end diastolic pressure (LVEDP, mmHg) was significantly increased (19.3 ±3.2, 9.8±1.6, p<0.05), and LV +dP/dt (mmHg/s, 7250±588, 9500±453, p<0.01) and -dP/dt (mmHg/s, 6000±433, 7781± 314, p<0.05) were significantly decreased in YAP-cKO compared to in control mice after TAC. LV end diastolic diameter (mm) was significantly greater in YAP-cKO than in control mice after TAC (3.95±0.11, 3.35±0.15, p<0.05), whereas LV pressure was similar, suggesting that LV wall stress was elevated in YAP-cKO compared to in control mice. Since cardiac hypertrophy in YAP-cKO mice is similar to that in control mice despite elevated wall stress, the lack of YAP appears to limit the extent of cardiac hypertrophy in response to increased wall stress.

These data suggest that endogenous YAP plays an important role in mediating adaptive hypertrophy and protecting the heart against PO.
Abstract 18119: Structural and Functional Right Ventricular Remodelling is Related to Training Intensity in an Experimental Model of Endurance Training
Authors: Sanz Maria , Rubies Cira , Sitges Marta , Battle Montserrat , Bijnens Bart , Mont Lluis , Brugada Josep , Guasch Eduard
Published: July 2021

Background:
a deleterious, potentially arrhythmogenic right ventricle (RV) remodelling has been documented in response to regular training in athletes. However, it is unclear how exercise intensity contributes to RV adverse remodelling.

Aim:
Our aim was to evaluate the relationship between RV functional and structural remodelling,and the intensity of exercise in an animal model.

Methods:
Thirty-six Wistar rats were conditioned to run daily in a treadmill at a moderate (MOD, 45 min at 30cm/s; estimated 60% VO2max) or vigorous (VIG, 60 min at 60cm/s; estimated 85-90% VO2max) intensity for 16 weeks; Sedentary rats (SED) served as controls. An standard echocardiographic assessment of both ventricles and Tissue Doppler Imaging (TDI) of the RV were performed. Hemodynamics of both ventricles were evaluated with a sensor tip pressure catheter.

Results:
After MOD training, both ventricles similarly dilated (roughly 15%). RV function improved as shown by increased RV apical function assessed by TDI (Figure).With VIG training, though, RV disproportionately dilated (in comparison to MOD: 10±13% RV dilation vs 1±12% LV dilation, p<0.05), RV systolic function declined, and RV diastolic function worsened (Figure).The hemodynamic experiments confirmed a decreased RV contractility and impaired relaxation with VIG training (Figure) in comparison to MOD. The LV systolic and diastolic function were unchanged in all groups.

Conclusion:
In this animal model we show that exercise intensity critically determines a dual response of the RV. A favourable adaptation of the RV after MOD training turned into disproportionate RV dilatation, decreased contractility and worse diastolic function in the VIG group. Our findings suggest the existence of an intensity threshold beyond which remodelling of the RV becomes maladaptive. Our work provides valuable data to identify athletes at risk of exercise related complications
Abstract 18122: Mir-206 Plays an Important Role in Mediating Pressure Overload-induced Cardiac Hypertrophy
Authors: Sciarretta Sebstiano , Yang Yanfei , Del Re Dominic P , Sadoshima Junichi
Published: July 2021

Introduction:
Expression of miR-206 is upregulated by YAP, a key transcription co-factor controlled by the Hippo signaling pathway, and mediates YAP-induced hypertrophy and survival of cardiomyocytes. Although miR-206 is known to promote hypertrophy of skeletal muscle, the role of miR-206 in the heart under clinically relevant conditions in vivo remains unknown. We investigated the role of miR-206 in mediating cardiac hypertrophy in response to pressure overload (PO).

Results:
The level of miR-206 in the mouse heart, as evaluated by qRT-PCR, was upregulated 2.9 fold (p<0.05) 7 days after transverse aortic constriction (TAC) compared to sham operation. In order to evaluate the involvement of miR-206 in cardiac hypertrophy, wild-type C57B/6J mice were administered LNA inhibitor designed to selectively inhibit miR-206, or control scrambled LNA, by tail vein injection. Specificity of the LNA inhibitor was confirmed by qRT-PCR analysis of miRNA expression 48 hours after treatment. Notably, the LNA inhibitor did not affect the level of miR-1, which has a sequence similarity with miR-206. After 48 hours, mice from both treatment groups were subjected to sham operation or TAC. After 7 days of TAC, echocardiography was performed and mice were sacrificed. Upregulation of myocardial miR-206 expression levels after 7 days TAC observed in LNA control-treated mice was completely abolished in LNA-anti-206 -treated mice. A significant increase in left ventricular weight/tibial length (mg/mm) in LNA control-treated mice following TAC was observed (sham vs TAC: 3.7, 4.8, p<0.05); however, no increase was observed in LNA-anti-206 -treated mice (3.8, 3.8). We also noted significant differences in chamber wall thickness (mm) between the LNA-control and LNA-anti-206-treated TAC groups (diastolic posterior wall 0.91, 0.61, p<0.05). Additionally, cardiomyocyte cross sectional area (1.23, 0.9, p<0.05) and ANF expression (2.5, 1.3, P<0.05) were significantly increased in the LNA control-treated TAC group, and these responses were attenuated in the LNA-anti-206-treated mice.

Conclusions:
These data demonstrate that inhibition of miR-206 impairs PO-induced hypertrophy and indicates that miR-206 is an important endogenous mediator of heart growth in response to PO.
Abstract 18157: Impact of Betatrophin (ANGPTL8) R59W Mutation for Future Diabetes, and Minimal Modification of Circulating Betatrophin With Strong Statins
Authors: Nohara Atsushi , Kawashiri Masa-aki , Hattori Hiroaki , Iwasaki Tadao , Liu Jianhui , Yagi Kunimasa , Yoshida Mie , Mori Mika , Nakanishi Chiaki , Tada Hayato , Inazu Akihiro , Kobayashi Takeshi , Yamagishi Masakazu , Mabuchi Hiroshi
Published: July 2021

Betatrophin (ANGPTL8), also known as “Lipasin” (lipoprotein lipase inhibitor), has been reported as a dual-regulator of glucose and lipid metabolism. Functional variant R59W in betatrophin gene is common in Japanese (minor allele 25%) compared with Caucasian (5%). Little is known about long-term impact of this gene variant, and also about the effect of lipid-lowering drugs on this hormone.

Methods:
A total of 205 cases with dyslipidemia evaluated with baseline 75gOGTT, and post-heparin lipoprotein lipase activities were registered as a long-term cohort. As lipid-lowering trial, a total of 44 patients (Male 21, Age 65±11 ys) with primary dyslipidemia, and 18 genetically confirmed heterozygous familial hypercholesterolemia (FH) (Male 12, Age 65±10 ys,) were analyzed. Non-FH dyslipidemia was treated with 10mg Atorvastatin, and FH was treated with 20mg Rosuvastatin for 8 weeks. Plasma TG and betatrophin levels were log-transformed for statistical analysis.

Results:
In long-term cohort, 57 cases already showed diabetic pattern at baseline, 148 cases (Male 82, age 56±15 ys, hetero-FH 48 cases, mean follow-up period 10±3 ys) without diabetes at baseline were finally analyzed. Sixty-two cases (42%) developed newly diabetes mellitus during the follow-up, significantly fewer in FH than non-FH (25% vs. 50%,
p
<0.005). No differences in BMI, fasting glucose, HbA1c in baseline with R59W genotype. In low LPL activity group (n=31), W carriers showed significant increase in HbA1c compared with RR (2.1±0.5 vs. 0.9±0.4 %,
p
<0.05), but no differences in normal LPL group.

In lipid lowering trial, baseline betatrophin levels were lower in FH group (19±13 vs. 13±6 ng/mL,
p
<0.05), but no difference with/without R59W variant. Statin treatment slightly decreased betatrophin in dyslipidemia group (-4%,
p
<0.01) and in FH group (-5%,
p
<0.01). Changes in betatrophin were positively correlated with changes in LDL-C with statins in both groups.

Conclusion:
Betatrophin R59W variant was a susceptibility factor of future diabetes mellitus with low LPL activity. Baseline betatrophin levels were lower in FH group than other primary dyslipidemia in lipid-lowering trial. Strong statin treatments slightly decreased betatrophin levels, but effect sizes were minimal.
Abstract 18184: Prognostic Value of Subjective and Objective Findings of Ischemia in Patients With Heart Failure
Authors: Ge Yin , Tu Jack V , Austin Peter C , Wang Xuesong , Lee Douglas S
Published: July 2021

Introduction:
Previous studies have shown that cardiac ischemia is a marker of poor prognosis in congestive heart failure. We determined the outcomes associated with subjective symptoms and objective findings of ischemia in patients presenting with acute heart failure.

Methods:
We studied 10,030 participants (mean age 76±12 years, 48% male) who presented to a hospital in Ontario, Canada with a primary diagnosis of acute heart failure. Using linked administrative databases, we analyzed the long-term impact of chest pain, ST segment depression, and positive troponin on vital status, hospital readmission, diagnostic testing, and coronary revascularization.

Results:
1,724 participants presented with symptoms of chest pain, of which 348 had objective evidence of cardiac ischemia (ST segment depression or positive troponin). Of the 8,306 participants without chest pain 1,602 had objective evidence of ischemia. At baseline, the chest pain cohort had higher proportion of participants with a history of heart failure, coronary disease, revascularization, and impaired LV function. In multivariate analysis, ST segment depression and positive troponin were associated with higher cardiovascular death (HR 1.11 and 1.41, both P<0.05), revascularization events (HR 1.41 and 1.48, both P<0.01), hospitalization for myocardial infarction (HR 1.35 and 1.69, both P<0.01) and heart failure (HR 1.08 and 1.15, both P<0.05). Rates of admission for non-cardiovascular hospitalization did not differ. The presence of chest pain was associated with increased use of diagnostic testing for ischemia (HR 1.14, P<0.01) and admission for ischemic symptoms (HR 1.10, P<0.05), but lower risk of cardiovascular death (HR 0.86, P<0.01 Figure 1).

Conclusions:
In this large, community-based cohort of patients presenting with acute heart failure, the presence of objective findings, but not subjective symptoms of ischemia, was associated with higher risk of major adverse cardiac outcomes.
Abstract 18299: Device Selection: Does Ventricular Size Matter in LVAD Recipients?
Authors: Shah Palak , Maltais Simon , Xu Meng , Desai Shashank S , Singh Ramesh , Haglund Nicholas A , Dunlay Shannon M , Stulak John M , Aaronson Keith D , Davis Mary B , Salerno Christopher , Pagani Francis D , Cowger Jennifer A
Published: July 2021

Introduction:
Axial and centrifugal-flow left ventricular assist devices (LVAD) have varied response to changes in loading conditions. Whether ventricular size modulates the response to LVAD therapy between the axial flow Heartmate II (HMII) and centrifugal flow Heartware (HVAD) is unknown.

Hypothesis:
Adverse event and survival rates between devices are affected by recipient pre-op left ventricular end-diastolic diameter (LVEDD).

Methods:
Data on 1,149 continuous-flow LVAD recipients from May 2004 to May 2015 was pooled from the Mechanical Circulatory Support Research Network (MCSRN). The effect of pre-op LVEDD on the instantaneous hazard of death and adverse events was evaluated between HMII (n=864) and HVAD (n=283).

Results:
The average LVEDD was 7.0cm and did not differ between the device recipients. Patients with a smaller LVEDD (≤ 6.3cm) were more likely female 39% v. 24% (p < 0.0001) and to have an ischemic cardiomyopathy (30% v. 24%, p = 0.045). For every 1cm increase in pre-op LVEDD, the adjusted hazard ratio (HR) for mortality increased with HVAD (HR 1.31, 95% CI 0.94-1.82, p = 0.005) and decreased with HMII (HR 0.78, 95% CI 0.67-0.92, p = 0.005), Figure 1a. Other predictors of mortality included age (HR 1.31, 95% CI 1.12 - 1.53 per 10y, p < 0.001) and bilirubin (HR 1.15, 95% CI 0.94-1.42 per mg/dL, p = 0.027). LVEDD by device type interaction was not a significant predictor of gastrointestinal bleeding or pump thrombosis. The risk of stroke increased with LVEDD for HVAD and decreased for HMII, but this did not reach statistical significance, Figure 1b. Ischemic etiology of heart failure (HR 1.7 95% CI 1.14 - 2.55, p = 0.01) and HVAD device use (HR 1.47 95% CI 1.00 - 2.17, p = 0.03) were significant predictors of stroke.

Conclusions:
Our data suggest important differences exist in patient outcomes between HMII and HVAD based on pre-op ventricular size. Studies are needed to determine if these differences in outcome are due to device or flow-specific differences in patient support.