bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18667: Lipoprotein(a) Catabolism and Apolipoprotein(a) Secretion is Regulated by Sortilin
Authors: Romagnuolo Rocco , Gemin Matthew , Koschinsky Marlys
Published: July 2021

Elevated levels of lipoprotein(a) (Lp(a)) in plasma have been identified as an independent, causal risk factor for coronary heart disease. Lp(a) consists of a low-density lipoprotein (LDL)-like particle whose apolipoproteinB-100 (apoB-100) moiety is covalently linked to the unique glycoprotein apolipoprotein(a) (apo(a)). Recently, Lp(a) internalization by the LDL-receptor (LDLr) in hepatic cells and primary human fibroblasts has been shown to be regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9). However, Lp(a)/apo(a) internalization still occurs even with a defective LDLr or in the presence of PCSK9 (in fibroblasts and hepatic cells, respectively), indicating a role for receptors other than the LDLr in Lp(a) catabolism. Hepatic sortilin has been identified as a potential receptor mediating LDL catabolism as well as the regulation of apoB-100 secretion. Sortilin localizes to the Golgi apparatus where it mediates trafficking of specific bound ligands to the lysosome. Sortilin also localizes to clathrin-coated pits in the plasma membrane where it can act as an internalization receptor. We demonstrate in the current study that Lp(a), but not apo(a), internalization in hepatic cells is influenced by sortilin overexpression. In the presence of PCSK9, Lp(a) internalization greatly increases with sortilin overexpression compared to control. These results suggest that hepatic sortilin has the ability to act as a receptor for Lp(a) catabolism, through the LDL-like moiety, in a manner that is not dependent on the LDLr. Furthermore, Lp(a) internalization increases with sortilin overexpression in primary human fibroblasts with a defective LDLr, again emphasizing an LDLr-independent role for sortilin as a receptor for Lp(a). Interestingly, an increase in apo(a) secretion is observed with sortilin overexpression in hepatic cells. Removal of the carboxyl-terminal tail of sortilin results in an inability to promote the secretion of apo(a), indicating a direct role for the sorting motifs present in this region of sortilin for the regulation of apo(a) secretion. Taken together, these results indicate novel roles for sortilin in both Lp(a) catabolism and apo(a) secretion.
Abstract 18672: Association Between Sleep Disordered Breathing and Electrocardiographic Markers of Atrial Abnormalities: The MESA Study
Authors: Kwon Younghoon , Misialek Jeffrey R , Duprez Daniel , Alonso Alvaro , Jacobs, Jr David R , Heckbert Susan R , Redline Susan , Soliman Elsayed Z
Published: July 2021

Introduction:
Abnormal P wave terminal force in V1 (PTFV1), an electrocardiographic marker of left atrial abnormalities, has been linked to increased risk of atrial fibrillation (AF). Examining the association between sleep disordered breathing (SDB) and PTFV1 might shed light on the potential mechanisms by which SDB increases risk of AF.

Methods:
A total of 1546 participants (mean age 67.2 (± 8.8) years, 53.4 % women and 63.3 % non-Whites) from the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 5 Sleep ancillary were included in this analysis. PTFV1 was measured from resting standard digital ECG tracings that were automatically processed centrally. Linear and logistic regression analyses were used to examine the cross-sectional associations between measures of SDB (apnea hypopnea index [AHI], obstructive AHI [OAHI] and % time spent with oxygen saturation <90% [% SpO2 90]) and PTFV1.

Results:
There was a trend of higher PFTV1 values across quartiles of AHI, OAHI and % SpO2 90 (p for trend <0.01 for each). In multivariable linear regression models, the upper quartile of AHI and OAHI measures were associated with higher values of PTFV1 compared with the lower quartile (Table). A 1-SD increase of AHI and OAHI were associated with increased levels of PTFV1 (Table). When PTFV1 was considered as a binary variable (using the cut point of 4000 μV.ms to define abnormality) in logistic regression analysis, AHI and OAHI were also associated with abnormal PTFV1.

Conclusion:
Severity of SDB, as measured by AHI is associated with subclinical left atrial disease, as measured by PTFV1. This could partially explain the reported association between SDB and AF.
Abstract 18710: Added Value of Electrocardiographic Signs and Symptoms to Improve Early Detection of Acute Coronary Syndrome in the Emergency Department
Authors: Zègre-Hemsey Jessica K , Burke Larisa A , DeVon Holli A
Published: July 2021

Background:
Early identification and diagnosis are critical in the management of patients with acute coronary syndrome (ACS) since time-dependent therapies reduce patient mortality and morbidity.

Objective:
The aims of this study were to describe differences in presenting symptoms by individual ACS diagnoses and determine the prognostic value of both signs (electrocardiographic evidence of ischemia) and symptoms for an ACS diagnosis.

Method:
Patients > 21 years old, with any ECG ischemic changes (ST-elevation, ST-depression, T-wave inversion), elevated serum troponin, and ACS symptoms presenting to one of five emergency departments (ED) were eligible for the study. Patients completed the ACS Symptom Checklist, a validated 13-item instrument that measures cardiac symptoms (typical and atypical). Pearson Chi-square tests were used for bivariate analyses and logistic regression was used for multivariate modeling.

Results:
A total of 1,031 patients (mean age 60
+
14, 62% male, 70% White) were enrolled; 450 (43.7%) were diagnosed with ACS. One hundred eleven (11%) had ST-elevation myocardial infarction (STEMI), 236 (23%) had non-ST elevation myocardial infarction (NSTEMI), 103 (10%) had unstable angina (UA), and 581 (56%) were ruled-out for ACS. Patients with STEMI were more likely to report chest pain, diaphoresis, and higher symptom distress (p<0.05) at presentation than those without. Patients with NSTEMI were more likely to report arm pain and patients with UA were more likely to report lightheadedness (p<0.05). The presence of any chest symptoms (OR 2.24; 95% CI 1.27-3.97), higher symptom distress (OR 1.07; 95% CI 1.0-1.15), and a lower number of symptoms (OR 0.92; 95% CI 0.86-0.98) were independent predictors of an ACS diagnosis (p<0.05). The strongest predictor of an ACS diagnosis was the presence of ECG ischemic changes (OR 4.51, 95% CI 3.20-6.36) adjusting for symptoms, age, gender, heart rate, arrhythmia, and troponin levels (p<0.001).

Conclusion:
ECG signs of ischemia combined with specific symptom characteristics may enhance timely triage and detection of ACS in the ED. Predictive models that incorporate presenting signs and symptoms should be explored for this vulnerable population.
Abstract 18719: Relationship Between Proximal Aorta Morphology and Progression Rate of Aortic Stenosis
Authors: Capoulade Romain , Bartko Philipp , Teoh Jonathan G , Teo Elisa , Park Yong H , Isselbacher Eric M , Sundt Thoralf , Macgillivray Thomas E , Hung Judy
Published: July 2021

Background:
Morphological changes of the proximal aorta, such as effacement of the sinotubular junction (STJ), may result in increased mechanical stress on the aortic valve leaflets and contribute to calcification and progression of aortic stenosis (AS). The aim of this study was to examine the association between abnormal morphology of proximal aorta and AS progression rate.

Methods:
Between 2010 and 2012, 426 patients with mild to moderate AS (peak aortic jet velocity >2.5 and <4 m/s) and LVEF≥50% with at least two years of follow up were included in this study. Aortic dimensions were measured at 3 different levels: sinus of Valsalva (SVal), STJ and ascending aorta (Aa). The ratios of SVal by STJ (SVal/STJ) and Aa by STJ (Aa/STJ) were used to determine degree of aortic deformity with smaller ratios consistent with greater perturbation of normal geometry. SVal/STJ<1.13 and Aa/STJ<1.09 were defined as significant low ratios per normal range reported in Guidelines. AS progression rate was assessed by annualized increase in mean gradient (MG; follow-up time = 3.2±0.8 yrs).

Results:
Mean age was 71±13 yrs and 64% were male. 16% had bicuspid aortic valve and MG was 21±8 mmHg. SVal, STJ and Aa dimensions were respectively 33±4 mm, 27±4 mm and 36±5 mm. Mean SVal/STJ ratio was 1.21±0.15 and Aa/STJ ratio was 1.29±0.19. Patients with significant low ratios had faster AS progression (p≤0.05; figure). After adjustment for age, gender, hypertension, diabetes, renal disease, bicuspid aortic valve, baseline MG, LVEF, aortic regurgitation and indexed STJ, SVal/STJ (p=0.025) or Aa/STJ (p=0.027) were independently associated with faster AS progression.

Conclusion:
Abnormal aortic root geometry such as effacement of the sinotubular junction is a strong and independent predictor of faster AS progression, regardless of arterial hemodynamics, aortic valve phenotype and baseline AS severity. This finding suggests an interrelation between proximal aorta morphology and stenosis progression.
Abstract 18747: Young Infants With Severe Tetralogy of Fallot: Early Primary Surgery versus Trans-catheter Palliation
Authors: Wilder Travis J , Van Arsdell Glen S , Benson Lee , Duong An , Pham-Hung Eric , Gritti Michael , Page Alexandra , Caldarone Christopher A , Hickey Edward J
Published: July 2021

Introduction:
Infants with severe tetralogy of Fallot (TOF) may undergo: 1) early primary surgical repair (EARLY) or 2) early catheter palliation (CATH) prior to delayed surgical repair. We compared these two strategies to 3) usual elective single stage TOF repair (USUAL).

Methods:
We studied 453 TOF repairs (2000-2012, excluding BT shunts). USUAL strategy at our institution is repair ≥3 months. Risk adjusted hazard analysis compared freedom from surgical or catheter reintervention. Somatic size, branch PA size and RV systolic pressure were modeled using 2543 echo reports via mixed model regression.

Results:
Table: group characteristics for USUAL (383), EARLY (42) and CATH (28). CATH involved: RVOT stent=18, RVOT balloon=9, ductal stent=1.

Risk adjusted freedom from surgical reoperation was 88%, 87% and 85% for USUAL, EARLY and CATH respectively, at 10 years. EARLY and CATH had similar reoperation rates, except for very young children (<1 month) where EARLY primary repair conferred increased risk of further surgery (Figure).

Risk adjusted freedom from catheter reintervention was higher for EARLY (76%) and especially so for CATH (53%) at 10 years, versus USUAL (83%; Figure).

Somatic growth and progression of RVSP (37-40mmHg) was similar among groups at 8 years. EARLY (P=.02) and CATH (P=.09) tend to have smaller bPAs initially. The CATH group tend to remain smaller in the long-term, whereas growth in EARLY matches USUAL.

Conclusions:
Early primary repair at very young ages comes with a cost of increased late surgical reoperation. Early transcatheter palliation tends to come with a cost of increased late transcatheter intervention - possibly related to slower branch PA growth.
Abstract 18782: Cardiac-specific Ablation of Ulk1, but not of Atg7, Attenuates Mitochondrial Autophagy in the Heart in Response to Energy Stress
(Best of Basic Science Abstract)
Authors: Saito Toshiro , Sadoshima Junichi
Published: July 2021

Rationale and Objective:
During myocardial ischemia, mitochondria in cardiomyocytes undergo oxidative stress, develop protein damage/dysfunction, and trigger cell death. Dysfunctional mitochondria are eliminated through mitochondrial autophagy (MA). MA is mediated by both Atg7-dependent (conventional) and independent (alternative) mechanisms. We investigated the molecular mechanism mediating MA in response to prolonged myocardial ischemia.

Methods and Results:
We subjected wild-type, cardiac-specific atg7 KO, and cardiac-specific ulk1 KO mice (WT, atg7cKO, or ulk1cKO, respectively) to 48-hour fasting. The protein level of LC3-II was increased more than 5-fold in WT and ulk1cKO mouse hearts in response to starvation (p<0.05), suggesting that conventional autophagy is induced. LC3-II was not detectable, and p62 was markedly accumulated in atg7cKO mouse hearts, indicating the complete absence of conventional autophagy in atg7cKO mouse hearts. Mitochondrial mass, as evaluated by the mitochondrial DNA content, was significantly increased in ulk1cKO mouse hearts (1.27-fold, p<0.05) in response to fasting, but not in WT nor atg7cKO mouse hearts. Electron microscopic analyses indicated that autophagosomes containing mitochondria were easily detected in WT and atg7cKO, but not in ulk1cKO, mouse hearts after fasting. These results suggest that Ulk1, rather than Atg7, is essential for mediating MA in response to fasting. We also subjected them to prolonged ischemia (2 hours). The size of myocardial infarction/area at risk was significantly greater in ulk1KO mouse hearts (67%, p<0.05) than in WT (37 %) and atg7cKO (40 %) mouse hearts. Although WT and atg7cKO mouse hearts exhibited a significant decrease in the protein level of COXI (0.81- and 0.82-fold, p<0.05) in the ischemic region, ulk1cKO mouse hearts exhibited an increase (1.27-fold, p<0.05). Through electron microscopy, MA was clearly observed at the ischemic area in WT and atg7cKO mouse hearts, but not in ulk1cKO mouse hearts.

Conclusions:
These results suggest that Ulk1, rather than Atg7, plays an important role in mediating protection of the heart against energy stress by mediating degradation of damaged mitochondria through MA.
Abstract 18790: Identification of a Novel Regulator of the Mesenchymal Stem Cell Secretome and Myocardial Repair
Authors: Dong Feng , Kiedrowski Matthew , Penn Marc , Mayorga Mary E
Published: July 2021

The delivery of mesenchymal stem cells (MSC) in acute myocardial infarction (AMI) leads to significant preservation of myocardium and improved cardiac function. We have previously shown that the down-regulation of the tumor suppressor protein disabled-2 (Dab2) leads to increased MSC function in AMI. We sought to define the molecular mechanisms associated with down-regulation of disabled-2 and improved MSC function. We observed that the improvement in cardiac function following engraftment of Dab2-/- MSC was associated with modulation of the MSC secretome, in that of conditioned media conferred the same benefits as cell transplantation. To begin to define the down-stream targets of disabled-2 we completed a detailed Illumina array comparing Dab2 down-regulation by three methods (MSC treated with TGFß1 or MSC transfected with miR-145 or dab2:siRNA). Comparing gene expression in these three treatment groups to control MSC we identified 23 genes whose expression were similarly significantly modulated by dab2 down-regulation. Of this group we have focused to date on CAMKK1 as a possible regulator of the MSC secretome. CAMKK1, is a kinase with multiple down-stream targets including CAMK1, CAMKIV and Akt. Inhibition of CAMKK1 leads to an increase in pro-inflammatory cytokines and chemokines in the conditioned media of MSC. To determine if CAMKK1 over-expression was sufficient to induce an MSC like benefit in AMI we generated a plasmid vector in which CAMKK1 expression is regulated by the CMV promoter and the 5’-UTR RU5 enhancer element. We performed randomized blinded study in an AMI model in Sprague Dawley rats in which 500 ug of plasmid encoding CAMKK1 in 5 divided doses was injected into the infarct borderzone immediately after LAD ligation. CAMKK1 over-expression led to a significant improvement in cardiac function at 1, 2 and 8 weeks after AMI (Ejection Fraction at 8 weeks: CAMKK1: 83.2%±5.4% vs. Placebo: 51.7%±5.8%, p<0.0001, baseline: 91.3%±4.3%). These data suggest that CAMKK1 is a key molecular regulator of the MSC secretome, and that the benefits associated with MSC therapy can be achieved through the direct over-expression of CAMKK1.
Abstract 18807: Use of Mechanical Circulatory Support and Transcatheter Aortic Valve Replacement (TAVR): Insights From Nationwide Inpatient Sample
Authors: Patel Samir V , Singh Vikas , Savani Chirag , Sonani Rajesh , Panaich sidakpal S , Patel Nileshkumar J , Lahewala Sopan , Patel Achint , Patel Nilay , Thakkar Badal , Arora Shilpkumar , Pau Dhaval , Desai Maheshkumar K , Jhamnani Sunny , Deshmukh Abhishek , Badheka Apurva O
Published: July 2021

Introduction:
Short-term use of Mechanical Circulatory Support (MCS) has the potential to benefit the patients undergoing Transcatheter Aortic Valve Replacement (TAVR) who may be high-risk or suffer complications. The present study was conducted to address the contemporary use of MCS in TAVR procedures.

Methods:
The study included a total of 1794 TAVR procedures in the years 2011-2012 from Nationwide Inpatient Sample (NIS) database. Use of MCS was identified using ICD-9-CM codes. The patients were divided based on use of MCS devices. The primary outcome of the study was in-hospital mortality and the secondary outcomes were complications, length of stay (LOS) and cost. Multi-variate simple logistic regression models were used to identify independent predictors of the outcomes.

Results:
Out of total 1794 TAVR procedures, 190 (10.6 %) utilized a MCS device (MCS group) and 1,604 (89.4%) did not (non-MCS group). The use of MCS devices with TAVR was associated with increase in the in-hospital mortality (14.9% vs. 3.5%, p<0.01) with same results obtained in multi-variate models. The rates of complications were significantly higher in MCS group so as the mean length of stay (11.8±0.8 vs. 8.1±0.2 days, p<0.01) and cost ($68,997±3,656 vs. $55,878±653, p=0.03).

Conclusion:
Use of MCS in TAVR predicts increase in-hospital mortality, complications, LOS and cost of care.
Abstract 18821: Dysfunctional Regulatory T-Lymphocytes Promote Inflammation and Adverse Cardiac Remodeling in Chronic Ischemic Heart Failure
Authors: Bansal Shyam S , Goel Mehak , Ismahil Mohamed Ameen , Hamid Tariq , Zhong Hai , Wu Yixin , Prabhu Sumanth D
Published: July 2021

The functional role of regulatory T-cells (Tregs) in chronic heart failure (HF) is unknown. Using flow cytometry, we assessed Tregs during the progression of ischemic HF in male C57Bl/6 mice after coronary ligation and myocardial infarction (MI). At 7 d post-MI, circulating Tregs (% CD4+ T-cells) were comparable to sham-operated mice. Thereafter, blood Tregs significantly (p < 0.05 vs sham) increased ~1.5 fold at 2, 4, 6, and 8 w, and exhibited increased levels of pro-inflammatory intracellular IFNγ (40.5 ± 5.9 vs 28.4 ± 5.1%) and TNFα (34.6 ± 8.8 vs 21.7 ± 6.9%). Moreover, at 8 w post-MI, Tregs were increased in the spleen (24.1 ± 3.9 vs 18.3 ± 1.4%) and failing heart (0.95 ± 0.42 vs 0.33 ± 0.23%) as compared with sham mice. In contrast to splenic Tregs from sham mice, Tregs isolated from HF mice (8 w post-MI) failed to suppress effector T-cell proliferation, and were robustly antiangiogenic as indexed by mouse coronary endothelial cell tube formation assays. Transgenic mice expressing diphtheria toxin (DT) receptor (DTR) under control of the Foxp3 promoter underwent coronary ligation and DT-induced selective Treg ablation starting at 4 w post-MI (PBS control). Echocardiography before and after (8 w post-MI) PBS or DT injection revealed that in contrast to progressive LV dysfunction and remodeling after PBS, DT-mediated Treg ablation and subsequent reconstitution reversed pathological LV remodeling (decreased EDV and ESV, and increased EF). As compared with PBS injection, DT-induced Treg ablation also significantly (p < 0.05) reduced LV hypertrophy; enhanced circulating CD34+Flk1+ cells, cardiac CCR5 gene expression, and myocardial capillary density; reduced border zone fibrosis; and decreased pro-inflammatory (IL-17, IL-2 and IL-6) and pro-fibrotic (IL-4 and IL-10) serum cytokines. Similar results were obtained upon Treg depletion with anti-CD25 antibody in HF. We conclude that Tregs in chronic HF acquire pathological pro-inflammatory, profibrotic, and antiangiogenic properties, and lose their immunosuppressive capacity. Dysfunctional Tregs promote inflammation and adverse LV remodeling in HF; depletion of dysfunctional Tregs and subsequent restoration to a normal Treg phenotype may represent a novel approach to therapeutic immunomodulation in HF.
Abstract 18838: The Impacts of Burst Exercise Compared to Sustained Exercise on the Cardiometabolic Status and Exercise Behavior of Newly Diagnosed Type 2 Diabetic Patients
Authors: Pandey Avinash , Poirier Paul
Published: July 2021

Introduction:
Physical activity is an integral part of type 2 diabetes (NIDDM) rehabilitation. Historically, NIDDM rehabilitation has employed low intensity, sustained exercise. Recent studies have demonstrated cardiometabolic benefits of high intensity burst exercise in healthy volunteers. The impacts of burst exercise in NIDDM have yet to be assessed. This study compared the impacts of burst and sustained exercises on cardiometabolic factors including: BMI, exercise adherence, cardiopulmonary fitness, HbA1C and lipid profiles in newly diagnosed NIDDM.

Hypothesis:
High-intensity burst physical activity may yield greater cardiometabolic benefits than low intensity, sustained exercise.

Methods:
This was a single center, single blind randomized trial. 76 patients, within three months of diagnosis of NIDDM, were recruited. Patients were randomized to a control group prescribed 30 minutes of exercise five days a week at 65% of target heart rate or an intervention group prescribed ten minutes of exercise three times a day, five days a week at 85% of target heart rate. All patients underwent routine blood tests, stress tests and logged exercise duration and frequency in logbooks. Patients were excluded from the study if they had evidence for diabetic end organ damage or cardiovascular disease, or took medications which would impact the cardiometabolic parameters assessed in this study.

Results:
Of 225 patients screened, 76 patients were recruited for the study with an average age of 67; 70% were male. No significant differences in demographics were noted between groups. Patients prescribed the burst regimen exercised 27% more than the control (p<0.01). Burst exercise patients also showed a 2.3 fold greater improvement in HbA1c (p<0.01). The intervention group also improved more in their lipid profile, BMI and cardiopulmonary fitness (as measured by stress testing). Linear regression analysis revealed greater improvements in both HbA1C and BMI with burst exercise than with sustained exercise, for the same duration of exercise.

Conclusions:
The burst exercise regimen significantly improved the cardiometabolic and fitness status of newly diagnosed NIDDM. This regimen may represent a simple and effective way to improve diabetes rehabilitation.
Abstract 18850: A Report on Cardiomyopathy and Arrhythmia Incidence in a Duchenne Muscular Dystrophy Cohort
Authors: Aslam Mohammed I , Thompson William R , Judge Daniel P , Nazarian Saman
Published: July 2021

Background:
With improved respiratory care and the increasing lifespan of patients with Duchenne Muscular Dystrophy (DMD), morbidity and mortality due to cardiac involvement and sudden cardiac death (SCD) have increased. Nevertheless, data regarding incidence of SCD and the appropriate management of cardiac involvement are sparse; evidence-based guidelines for arrhythmia management in DMD do not exist. We sought to define the characteristics of electrocardiography, cardiac imaging abnormalities, association of therapeutic practices with cardiomyopathy and arrhythmia in a cohort with DMD.

Methods and Results:
A retrospective review of our current institutional electronic medical records (EMR) identified 125 DMD patients aged 10 or older. Electrocardiography was performed at least every 3 years or as prompted by symptoms. Symptom-prompted and baseline echocardiography, cardiac magnetic resonance (CMR) and Holter monitor data were extracted. Cardiac medical therapy primarily consisted of an angiotensin-converting-enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB; 98.4%) and beta-blockade (44.2%). As of May 2015, 115 of the 125 patients were living as determined by EMR. Left ventricular (LV) dysfunction was present in 52% of patients by age 18.7±5.9 years. Of 16 patients with LV dysfunction that underwent CMR, 13/16 had late gadolinium enhancement (LGE). Importantly, myocardial LGE was noted in 9 of 14 patients with normal LV function. The predominant ECG abnormality was tall R waves in V1, and Q waves in lateral precordial leads. Of 43 patients with Holter monitoring, 5 patients had non-sustained ventricular tachycardia and 5 had supraventricular tachycardia. Of 8 patients with an implantable cardioverter defibrillator (ICD), 1 died due to pulseless electrical activity. ICD placement was pursued in those with NSVT, persistently low EF or FS when patient preference allowed.

Conclusions:
ACEi or ARB use was universal in our DMD cohort. Evidence of LGE on CMR was noted in DMD patients with and without LV dysfunction. ECG characteristics did not appear to have a clinical impact. Future studies to examine the association of LGE and other clinical variables with SCD are warranted.
Abstract 18860: The Diagnostic Utility of Risk Factors Defined by the AHA/ACCF Expert Consensus Statement on the Evaluation of Cardiac Disease in Liver Transplantation Candidates
Authors: Teshome Meron K , Alexander Sarah , Patel Hena , Alkhalil Ahmad , Chan Edie , Doukky Rami
Published: July 2021

Introduction:
The 2012 AHA/ACCF consensus statement regarding cardiac evaluation of liver transplant (LT) candidates specifies 7 risk factors for identifying candidates for cardiac evaluation prior to LT. These include age >60 yrs, hypertension, diabetes, smoking, dyslipidemia, prior cardiovascular disease, and left ventricular hypertrophy. The document issued a Class IIb, LOE C recommendation for noninvasive testing in asymptomatic LT candidates who have “multiple” risk factors but did not define the number of risk factors required to prompt evaluation, suggesting that ≥3 risk factors may be “reasonable”.

Hypothesis:
Risk factors set forth by the AHA/ACCF can predict significant coronary artery disease (CAD) in LT candidates. We sought to identify a threshold sum of risk factors that should prompt CAD evaluation.

Methods:
Consecutive LT recipients who underwent pre-operative coronary angiography were analyzed. Logistic regression model and ROC curves were used to determine the predictive value of the sum of risk factors in predicting presence of CAD.

Results:
Among 45 consecutive patients (44% female; mean age 57±8 yrs) with coronary angiogram prior to LT, 15 had significant CAD (≥50% stenosis) and 13 had severe CAD (≥70% stenosis). The sum of risk factors was strongly predictive of significant CAD (OR, 7.12 per 1 risk factor increment; CI, 2.13-23.73;
P
= 0.001). ROC analyses demonstrated that the sum of AHA/ACCF risk factors was associated with AUC of 0.89 and 0.88 for significant and severe CAD, respectively (Fig 1). A threshold of ≥2 risk factors provided 100% sensitivity and 60% specificity for severe CAD, while a threshold of ≥3 had inferior sensitivity (Fig 1).

Conclusion:
This study represents a diagnostic validation of the risk factors set forth by the 2012 AHA/ACCF consensus statement. A threshold of ≥2 risk factors seems optimal for identifying candidates for noninvasive cardiac evaluation in asymptomatic LT candidates.
Abstract 18867: Multiple Pregnancy Factors and Serum Lipids at Age 40 Year in Swedish Women From the Vasterbotten Intervention Programme
Authors: Parikh Nisha , Norberg Margareta , Ingelsson Erik , Cnattingius Sven , Ramachandran Vasan , Domellöf Magnus , Edstedt Bonamy Anna-Karin
Published: July 2021

Introduction:
Pregnancy factors provide an early window into future cardiovascular disease (CVD) risk in women. It is uncertain which factors, when considered together, independently relate to later lipid levels.

Methods:
We used Swedish National Medical Birth Register data linked with the Vasterbotten Intervention Programme cohort. We related pregnancy factors (in any pregnancy) with serum lipid levels at age 40 years in parous women. Using linear regression analysis in crude and multivariable adjusted models, we related total parity, age at first delivery, infertility ≥ 5 years, preeclampsia, small for gestational age (SGA), preterm delivery, placental abruption and gestational diabetes to each of the four clinical lipid variables (total cholesterol, triglycerides HDL-C and LDL-C). HDL-C and LDL-C were measured in a smaller subset of women. Multivariable models were adjusted for all pregnancy factors in addition to annual income, education, smoking status, alcohol intake and body mass index.

Results:
In multivariable models, lower parity and younger age at first birth were related to increased total cholesterol (Table). Lower parity, younger age at first birth, gestational age < 37 weeks, and infertility ≥ 5 years were related to increased triglycerides. Preeclampsia was related to increased triglyceride and lower HDL-C only in crude models. Gestational diabetes was related to total cholesterol, triglyceride and lower HDL cholesterol in crude models only. SGA was related to total cholesterol and triglycerides in crude models only. Placental abruption was not associated with any lipid measures in either crude or multivariable models.

Conclusions:
Lower parity, younger age at first birth, a history of prolonged infertility prior to pregnancy and preterm delivery are independently related to alterations in lipid levels at age 40 years in women. The association between preeclampsia and later CVD does not appear to be independently mediated by dyslipidemia.
Abstract 18944: Efficacy of Clinical Notifications to Health Care Providers in Management of Heart Failure Patients
Authors: Akhavein Reyhaneh M , Sklenar Jiri , Minnier Jessica , Heitner Stephen
Published: July 2021

Introduction:
Adherence to guideline recommendations for patients with heart failure improves short and long-term outcomes, and can potentially reduce healthcare costs.

Hypothesis:
Written communication to care providers of individuals with heart failure with reduced systolic function (HFrEF) will result in better adherence to guidelines.

Methods:
We prospectively enrolled providers of all outpatients with HFrEF at Oregon Health and Science University in 2012. We reviewed adherence to six evidence-based HF therapies in each patient [ACE-I/ARB, beta blocker, aldosterone antagonist, anticoagulation therapy for atrial fibrillation or flutter, CRT, and ICD]. We excluded patients with destination therapy, resolution of HFrEF, lost to follow-up or death. After implementation of exclusion criteria, of 320 patients evaluated, 114 patients were ultimately included. These patients’ providers were randomized to either receiving a standardized written communication (intervention) or none (control). The letter highlighted 2013 ACCF/AHA heart failure management guidelines, and was sent by US mail to providers in intervention group. Six months later, we re-evaluated all patients according to the same criteria at the outset.

Results:
Optimal medical therapy (OMT) in intervention group improved in only 9% of patients who were previously sub-optimally treated (p 0.83), but 31% of patients who had already been on OMT experienced deescalated therapies despite no clear documentation (p 0.65). In control group, 11% of patients had increased treatment according to guidelines, and 9% of patients who had already been receiving OMT had deescalated treatment. There were no new ICDs implanted as a result of intervention, while 6.5% of patients in control group did receive ICD (p 0.46).

Conclusions:
Identification of patients with HFrEF and assessment of adherence to guideline-based therapies is now feasible via electronic medical record enquiry. Written notifications do not result in improved adherence to evidence-based guidelines, nor do these letters seem to alter provider behavior at all. We speculated that the lack of response is a direct result of “notification-fatigue”, and that alternative provider behavior modification techniques need to be evaluated.
Abstract 18946: Frequency of Unidentified Cause of Death in Sudden Unexpected Death: A Post-mortem Retrospective Study From Asian Population
Authors: Rattanawong Pattara , Vutthikraivit Wasawat , Kanjanahattakij Napatt , Ngarmukos Tachapong , Srisont Smith
Published: July 2021

Introduction:
Sudden unexpected death (SUD) is the leading cause of death worldwide. Although coronary atherosclerosis is a major cause of SUD, standard autopsy may not explain the cause of SUD. The frequency of unidentified cause of death in Thailand is not known. Therefore, we conduct a retrospective study to address the frequency of unidentified cause of death in SUD of Thailand.

Hypothesis:
The frequency of unidentified cause of death in SUD of Thailand could be higher than Caucasian.

Methods:
We reviewed autopsy reports of SUD in Ramathibodi Hospital, Mahidol University, Thailand, during January 2012-December 2013. The autopsy reports were excluded if; (1) the age was over 65 or under 18 years; (2) the death was expected death: e.g. the decease was in hospice care; (3) the cause was an obvious non-cardiac cause: e.g. trauma, overdose, or pneumonia; (4) the decease was not Thai citizen.

Results:
A total of 116 cases, 108 males (93.1%) and 8 female (6.9%), were included. The mean age was 49.7±15.2 years. The cause of death was identified as ischemic heart disease in 74 cases (63.8%), which 32 cases (27.6%) were significant coronary atherosclerosis without infarction, 23 cases (19.8%) were acute myocardial infarction, and 19 cases (16.4%) were old myocardial scaring. The causes of death were due to myocardial bridging in 8 cases (6.9%), isolated left ventricular hypertrophy in 6 cases (5.2%), hypertrophic cardiomyopathy in 3 cases (2.6%), and myocarditis in 2 cases (1.7%). Other causes were 1 case (0.9%) of obesity cardiomyopathy, 1 case (0.9%) of aortic stenosis, and 1 case (0.9%) of dilated cardiomyopathy. Interestingly, the cause of death was not clearly identified in 20 cases (17.2%) from standard autopsy, including 5 cases (4.3%) without any co-morbidity, 6 cases (5.2%) with non-significant atherosclerosis, 4 cases (3.4%) with non-toxic level of prescribed drugs, 3 cases (2.6%) with non-toxic level of alcohol, and 2 cases (1.7%) with history of epilepsy.

Conclusions:
We demonstrated higher frequency of unidentified cause of death in Thai SUD compared to Caucasian, as well as frequency of myocardial bridging. However, the frequency of ischemic heart disease was lower. Further incidence study and molecular autopsy of SUD should be conducted in Asian population.
Abstract 18957: Modulation of Ganglionated Plexi as an Addition to Pv Isolation in Persistent Atrial Fibrillation Ablation
Authors: Ernst Sabine , Underwood Richard , Babu-Narayan Sonya , Ben-Haim Simona
Published: July 2021

Introduction:
Catheter ablation of ganglionated plexi (GP) as an add on to pulmonary vein (PV) isolation has been reported to significantly improve outcome of atrial fibrillation (AF) ablation. In order to facilitate localization of these GPs, a novel imaging study is proposed that investigates the uptake of iodine-123 metaiodobenzylguanidine (mIBG, an analogon for norepinephrine) on the atrial level. This information is combined with 3D surface reconstruction from contrast computed tomography (cCT) or cardiac magnetic resonance (CMR).

Methods:
A total of 7 patients (5 male, mean age 64.3 yrs) with AF underwent mIBG nuclear studies using a dedicated solid state cardiac camera (D-SPECT, Spectrum Dynamics). Four patient had 4 persistent AF (3 prev. abl.) with less than 1 year of sustained AF, whereas 3 patient were in longstanding persistent AF (all prev. abl). The acquired data was merged with the 3D imaging and subsequently imported into the 3D electroanatomical mapping system (CARTO, Biosense Webster). During invasive AF ablations these sites were mapped to perform high frequency stimulation (HFS) to confirm GP locations.

Results:
In all pts, both the mIBG and CT scans were performed without any complications. Locations of high mIBG uptake corresponded to anatomical GP sites (LA & RA) in the majority of patients, but individual variations were observed. PV isolation was added in all but 1 pt (who had previous ablation) plus CFAE ablation if necessary. Follow-up of in median of 10.4 months demonstrated SR in all persistent AF patients (1 redo for atrial reentry). In patients with longstanding persistent AF: 2 pts are in SR (both AF at 1 week and 1 pt in AT at 6 weeks), while 1 pt remained in AF.

Conclusion:
The combination of mIBG and 3D imaging provides a novel type of “road map” for localizing GPs during AF ablation. As an add-on to PV (re-) isolation, this strategy was found to be beneficial for patients with persistent and longstanding persistent AF. Interestingly, pts with longstanding persistent AF (and multiple previous ablations) all recurred early in F/U but showed reversal to AT and finally SR at later stages. Further studies in larger patient cohorts need to confirm these initial observations.
Abstract 18995: Statins in Familial Hypercholesterolemia - Effects on Coronary Artery Disease and All-cause Mortality
Authors: Besseling Joost , Hovingh Gerard K , Kastelein John J , Hutten Barbara A
Published: July 2021

Introduction:
Heterozygous familial hypercholesterolemia (heFH) is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk for premature coronary artery disease (CAD) and death. Reduction of CAD and mortality by statins has not been properly quantified in heFH. The aim of the current study is to determine the effect of statins on CAD and mortality in heFH.

Methods:
All adult heFH patients identified by the Dutch FH screening program between 1994 and 2014 and registered in the PHARMO Database Network were eligible. Of these patients we obtained hospital, pharmacy (in- and outpatient), and mortality records in the period between 1995 and 2015. The effect of statins (time-varying) on CAD and all-cause mortality was determined using a Cox proportional hazard model, while correcting for the use of other lipid-lowering therapy, thrombocyte aggregation inhibitors, antihypertensive and antidiabetic medication (all time-varying). Furthermore, we used inverse probability for treatment weighting (IPTW) to account for differences between statin-treated and untreated patients regarding history of CAD before follow-up, age at start of follow-up and age of screening, as well as body mass index, LDL-C and triglycerides.

Results:
Of the 25,479 identified heFH patients, 11,021 gave informed consent to obtain their medical records, of whom 2,447 could be retrieved. We excluded 766 patients younger than 18. The remaining 1,681 heFH patients comprised our study population and these had very similar characteristics as compared to the 23,798 excluded FH patients, e.g. mean (SD) LDL-C levels were 214 (74) vs. 203 (77) mg/dL. Among 1,151 statin users, there were 133 CAD events and 15 deaths during 10,115 statin treated person-years, compared to 17 CAD events and 9 deaths during 4,965 person-years in 530 never statin users (combined rate: 14.6 vs. 5.2, respectively, p<0.001). After applying IPTW to account for indication bias and correcting for use of other medications, the hazard ratio of statin use for CAD and all-cause mortality was 0.61 (0.40 - 0.93).

Conclusions:
In heFH patients, statins lower the risk for CAD and mortality by 39%.
Abstract 19004: Contact Force Recovery Predicts Absence of Cardiac Perforation During Steam Pop Formation
Authors: Ganapathy Anand V , Nazeri Alireza , Ganapathy Krithika S , Razavi Mehdi
Published: July 2021

Introduction:
Cardiac perforations (CP) are an uncommon complication of radiofrequency ablation (RFA) that has profound clinical importance. We previously published results showing that the presence of contact force recovery after a steam pop occurs can be used to predict the absence of perforation in the absence of pericardium. Now, we aimed to determine if this relationship exists with the pericardium present, validate our results from the previous study, and determine the effects pericardium has on RFA.

Methods:
A 7.5F Thermocool Smarttouch force-sensing catheter (Biosense Webster Inc., Diamond Bar, CA) was used to perform left atrial RFA under direct observation in five open-chest sheep. The catheter’s contact force was measured every 50 ms during RFA. After each steam pop, the presence (+) or absence (-) of CP was noted as well as if pericardium was present or not over the ablation site. The contact force signals were then analyzed to determine if contact force recovery was present. In addition, the rate of perforation in the presence or absence of pericardium was also compared.

Results:
A total of 86 steam pops occurred (Table 1); 62 with pericardium and 24 without pericardium. For the pericardial data, contact force recovery was seen in 16 of the 49 CP- cases (33%) and 0 of the 13 CP+ cases (0%), p = 0.03. For the nonpericardial data, contact force recovery was seen in 6 of the 14 CP- cases (43%) and 0 of the 10 CP+ cases (0%), p = 0.02. The rate of cardiac perforation was 21% with pericardium and 42% without, p = 0.05. Pericardial tissue showed extensive charring during steam pops, even in the absence of CP.

Conclusions:
Contact-force recovery predicts the absence of CP during RFA independent of the presence or absence of the pericardium, confirming prior work. Our results suggest the pericardium decreases the likelihood of perforation, perhaps by acting as a thermal sink. Further studies are needed to correlate these results with clinical experiences.
Abstract 19011: Initial Field Testing of a Cloud-based Cardiac Auscultation Information Management System in Rural Southwest Kunming Province, Peoples Republic of China
Authors: Pyles Lee A , Pan Jihua , Yu Xiaoju , Liu Ke , Wang Jing , Zheleva Bistra , Tsakistos Andreas , Shao Weiguang , Hemmati Pouya , Ni Quan
Published: July 2021

Introduction:
Auscultation (Ausc) is used around the world to screen for congenital heart disease (CHD). We describe initial field testing of a cloud-based Ausc information management system in rural China school children with limited access to cardiac care . Our goal is to develop an economical system to facilitate access to cardiac care for underserved children in low- and middle-income countries.

Hypothesis:
Web/cloud based distant transmission of auscultation exam can facilitate screening for congenital heart disease.

Methods:
A team of cardiology staff from a tertiary hospital conducted field screening for CHD) in rural school children in Yunnan Province, People’s Republic of China. Each child with a murmur with traditional Ausc underwent echo screening and digital Ausc (Thinklabs, USA). Heart sounds were collected from 5 positions (URSB, ULSB, LLSB, apex and mid-LSB), and uploaded to a server using a tablet application (HeartLink System, USA). Blinded Ausc 3-5 months later was compared with echo finding at on-site screening.

Results:
8000 children were screened with standard Ausc over 4 days by a team from Kunming Medical University and First University Hospital. Heart sounds were recorded for 149 subjects. The best vibratory quality of an innocent Still murmur was heard at LLSB in 52,at mid-LSB in 51, apex in 10 and URSB/ULSB in 4. Digital Ausc found pathologic murmurs in 11 of 14 subjects with echo-diagnosed CHD. Three missed were ASD called venous hum in 2 of 3; likely related to respiratory artifact at the URSB/ULSB. Accuracy was 136/149 or 91% with 10 false positive. Positive predictive value 52% and negative predictive value 98%. The graphical phonocardiogram facilitates visual analysis of S2 splitting and the duration and timing of the cardiac murmur.

Conclusions:
The cloud-based digital Ausc system is able to collect, transmit, organize and display phonocardiograms for remote CHD screening and consultation. Difficulty with respiratory contamination of the signal is noted. VSD and Still murmur were successfully differentiated. The visual phonocardiographic display can aid S2 analysis for splitting. The pilot study demonstrates the potential use of this system to extend pediatric cardiology expertise to underserved rural areas around the world.
Abstract 19100: Transmural and Lateral Remodeling of the Post-infarction Scar Tissue: Serial Cardiac Magnetic Resonance Imaging Study From the Metocard-Cnic Trial
Authors: Jimenez-Blanco Marta , Lorca Rebeca , García-Ruiz Jose Manuel , Pizarro Gonzalo , Fernández-Jiménez Rodrigo , García-Álvarez Ana , Fernández-Friera Leticia , Fuster Valentin , Ibanez Borja
Published: July 2021

Background:
The remodeling process that occurs following an acute myocardial infarction produces changes in the myocardial scar and the surrounding tissue. The spatial evolution of the scar has not been yet characterized using MRI.

Purpose:
To describe the spatial behavior of myocardial scar on its transmural and lateral dimensions following an acute myocardial infarction.

Methods:
A total of 220 patients with acutely reperfused anterior STEMI (METOCARD-CNIC trial population) were studied. All the patients underwent cardiac MRI at day 7 and 6 months after presentation. The spatial distribution of the scar was analyzed using short axis late gadolinium enhancement images. Endo and epicardial contours of each LV short axis slice was traced, and each one was divided by 100 cords for analysis (Figure 1A). The lateral extension was defined as the percentage of cords with enhancement in every slice, and the transmural extension as the percentage of enhancement within each cord, nested in the lateral extension (Figure 1B). All slices were weighed according to their relative mass. Data were compared by paired t test.

Results:
Six months after STEMI, myocardial scar was smaller in both dimensions (Figure 1C). Mean ± SEM lateral scar, as a percentage of cords affected, at 7 days and 6 months were, respectively, 27.9 ± 1.1 and 22.2 ± 1.0 (p < 0.001). Transmurality also decreased significantly, mean percentage at day 7 was 46.8 ± 1.5 and at 6 months 35.4 ± 1.4 (p < 0.001). All these changes were accompanied by an increase in LV end-diastolic volume (171.47 ± 2.5 and 190.61 ± 2.9 (p < 0.001)).

Conclusions:
The myocardial scar remodeling process following a STEMI includes a reduction in both its transmural and lateral extensions.