bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14198: Anatomic Repair of Congenitally Corrected Transposition of the Great Arteries is Associated With Significant Mid- and Long-term Electrophysiologic Morbidity
Authors: Hartog Rebecca R , Watkins Kimberly J , Wilde Megan , Lim Tiffany R , Rodenbarger Andrew , Yu Sunkyung , Lowery Ray , Afton Katherine , Goldberg Caren S , Ohye Richard G , LaPage Martin J
Published: November 2020

Introduction:
Limited data exist on the electrophysiologic outcomes of patients undergoing anatomic repair (AR) for congenitally corrected transposition of the great arteries (ccTGA). AR was defined as an atrial switch procedure plus either arterial switch (ASO) or Rastelli operation.

Aims:
To report mid and late electrophysiologic outcomes after AR and identify risk factors for those outcomes.

Methods:
Single center retrospective cohort study of patients undergoing AR between 1993-2017. Data were collected from available records. Transplant-free survival to 1 year post repair was required for inclusion. Standard descriptive statistical analysis and Cox proportional hazards were used.

Results:
Of 85 patients included, 95% had lesions in addition to ccTGA: most commonly VSD (84%) and pulmonary stenosis or atresia (58%). Median age at AR was 1.5y (IQR 0.9-2.8) with Senning/ASO in 56%, Senning/Rastelli in 38%, and hemi-Senning/Glenn/Rastelli in 6%. During a median follow-up of 10.6y, 45 (53%) patients developed an arrhythmia requiring intervention. Atrial tachycardia (AT) in 27 (32%) or ventricular tachycardia (VT) in 11 (13%) patients required intervention at a median of 7.4y (IQR 1.6-15.3y) and 15.9y (IQR 4.5-17.9) post-AR, respectively. Treatments included chronic medications in 29 (64%), cardioversion in 15 (33%) and catheter ablation in 10 (22%). Median freedom from AT and VT was 17.3y and 25y post-AR, respectively. D-looped ventricles (p=0.03) and multiple operations prior to AR (p=0.02) were associated with increased AT risk; and native pulmonary stenosis with increased VT risk (p=0.01). Those needing heart failure/transplant referral had increased risk of both AT and VT (both p=0.04).

Pacemaker was implanted for heart block and/or SND prior to or during AR in 14 (16%), immediately post-op in 9 (11%), and late (median 6y post-AR) in 24 (28%). ICDs were implanted in 5 (6% of cohort), 4 for primary prevention. No patient had an appropriate shock.

Conclusions:
Anatomic ccTGA repair is associated with significant electrophysiologic morbidity. AT, VT, and SND develop at a similar incidence to that reported for d-TGA patients after atrial switch. The incidence of AV block follows a similar trajectory to that of physiologically palliated ccTGA.
Abstract 14500: Physical Activity in Individuals With the Long Qt Syndrome: Baseline Data From the Lifestyle and Exercise in Long Qt Study (live Lqts)
Authors: Lampert Rachel J , Day Sharlene , Marino Bradley S , Burg Matthew , Ainsworth Barbara , Tome Maite , Etheridge Susan P , Abrams Dominic J , Aziz Peter F , Cerrone Marina , Czosek Richard J , Erickson Christopher C , Gray Belinda , Johnsrude Christopher , Kannankeril Prince J , Law Ian H , McClellan Rebecca , Molossi Silvana M , Perez Marco V , Sanatani Shubhayan , Shah Maully S , Skinner Jonathan , Ware James S , Webster Gregory G , Li Fangyong , Simone Laura , Barth Cheryl , Harmon Kim , Hall Kevin , Olshansky Brian , Estes Mark , TOMASELLI Gordon F , Link Mark S , Saarel Elizabeth , Cannom David S , Ackerman Michael J
Published: November 2020

Introduction:
The safety of vigorous exercise for individuals with appropriately-treated LQTS remains unproven, and physical activity practices in this population have not been described.

Methods:
LIVE-LQTS prospectively enrolled individuals age 8-60 years with overt LQTS or gene mutation carriers. Participants (or parents, for children) answered surveys describing activity patterns. Vigorous exercise was defined as
>
6 METS for
>
60 hours per year. Clinical and demographic data were derived from medical record review.

Results:
Among 1554 participants, 804 (52%) reported exercising vigorously, 473 of these competitively, 577 (37%) exercising at moderate, and 173 (11%) at low levels. Seven percent of those working describe jobs more active than walking, including 10 in protective services and 19 in sports/coaching. Over 90% are genotype positive, 57% are phenotype positive at rest and an additional 16% have exercise-induced QT prolongation. Forty four percent have had documented ventricular arrhythmias or syncope. Eighty-four percent are appropriately treated with either beta-blockers, ICD, and/or sympathectomy, although among beta-blocked patients, only 60% are on the most effective agents. Among adults, BMI was significantly lower among the vigorous exercisers.

Conclusion:
While the high percentage of vigorous exercisers seen in this study may not represent all patients with LQTS due to self-selection for study participation, many patients with LQTS are engaged in vigorous exercise or competitive athletics. Prospective follow up of this cohort is ongoing and will determine safety of vigorous exercise through comparison of arrhythmic outcomes in vigorous exercisers vs moderate/low level exercisers.
Abstract 14505: Risk Reclassification by Circulating Immune Markers in Ambulatory Us Adults Without Prevalent Cardiovascular Diseases: Insights From National Health and Nutrition Examination Survey
Authors: Gupta Kartik , Kalra Rajat , Pate Mike , Nagalli Shivaraj , Ather Sameer , Arora Pankaj , Gupta Ankur , Zhou Wunan , Estepar Raul , DI CARLI MARCELO , Prabhu Sumanth D , Bajaj Navkaranbir S
Published: November 2020

Introduction:
Inflammation is associated with worse cardiovascular (CV) prognosis. We evaluated the impact of adding elevated monocyte lymphocyte ratio (MLR) to 10-year atherosclerotic CV disease (ASCVD) risk score.

Hypothesis:
Adding elevated MLR improves risk classification by 10-year ASCVD risk score.

Methods:
We used data from 6 cycles of NHANES (1999-2010) to identify ambulatory US adults aged ≥ 18 years without prevalent cardiovascular disease and total leukocyte count in normal range (4,000-11,000 cells/μL). Elevated MLR (≥0.3) was defined using optimal cutoff to predict CV mortality by Youden index. CV mortality was derived from linked National Center for Health Statistics data. We compared the change in reclassification of the 10-year ASCVD risk score at a pre-specified cutoff of 5% (low risk) and reported the net reclassification index (NRI). We further compared predictive value of the circulating immune with risk factors in ASCVD risk score using time-to-event and logistic models.

Results:
Among 21,599 eligible participants with median age 47 years (IQR, 34, 63; 49.2% women and 49.5% non-Hispanic White), there were 627 CV deaths with annual incidence rate of 0.3% over median follow-up of 9.6 years (IQR 6.8, 13.1). Median ASCVD risk score was 5% (IQR 1.6, 16.7). Adding elevated MLR to categorical 10-year ASCVD risk score correctly up classified 3.2% participants with CV mortality and incorrectly up classified 0.4% participants with no CV mortality. There was significant improvement in risk classification (NRI 2.7±1.4%, p=0.044, Panel A). Adding elevated CRP (≥0.3 mg/dL) did not change risk class (NRI -0.2±0.0%, p=827, Panel B). Among ASCVD components, MLR had higher predictive value than race, smoking, high-density lipoprotein, and total cholesterol in both time-to-event and logistic models.

Conclusions:
Elevated MLR significantly improves CV risk reclassification in ambulatory adults without prevalent CV disease and is better than CRP.
Abstract 14508: Development of a Risk Prediction Model for 1-year Readmission Among Younger Adults Hospitalized for Acute Myocardial Infarction
Authors: Dreyer Rachel P , Murphy Terrence E , Raparelli Valeria , Tsang Sui , Onofrio Gail , Lorenze Nancy P , Pilote Louise
Published: November 2020

Introduction:
Although readmission over the first year following hospitalization for acute myocardial infarction (AMI) is common among younger adults (18-55 yrs), there is no available risk prediction model for this age group. Existing risk models have been developed in older populations, have modest predictive ability, and exhibit methodological drawbacks. We developed a risk prediction model that considered a broad range of demographic, clinical, and psychosocial factors for readmission within 1-year of hospitalization for AMI among young adults.

Methods:
Young AMI adults (18-55 yrs) were enrolled from the prospective observational VIRGO study (2008-2012) of 3,572 patients. Data were obtained from medical record abstraction, interviews, and adjudicated hospitalization records. The outcome was all-cause readmission within 1-year. We used a two-stage selection process (LASSO followed by Bayesian Model Averaging) to develop a risk model.

Results:
The median age was 48 years (IQR: 44,52), 67.1% were women, and 20.1% were Non-white or Hispanic. Within 1-year, 906 patients (25.3%) were readmitted. Patients who were readmitted were more likely to be female, black, and had a clustering of adverse risk factors and co-morbidities. From 61 original variables considered, the final multivariable model of readmission within 1-year of discharge consisted of 14 predictors
(Figure)
. The model was well calibrated (Hosmer-Lemeshow P >0.05) with moderate discrimination (C statistic over 33 imputations: 0.69 development cohort).

Conclusion:
Adverse clinical risk factors such as diabetes, hypertension and prior AMI, but also female sex, access to specialist care, and major depression were associated with a higher risk of readmission at 1-year post AMI. This information is important to inform the development of interventions to reduce readmissions in young patients with AMI.
Abstract 14515: The Prognostic Impact of Human Epididymis Protein 4 Levels in Patients With Dilated Cardiomyopathy
Authors: OKUMURA Takahiro , Oishi Hideo , Kimura Yuki , Araki Takashi , Mizutani Takashi , Kazama Shingo , Shibata Naoki , Kuwayama Tasuku , Hiraiwa Hiroaki , Kondo Toru , Morimoto Ryota , Takefuji Mikito , Murohara Toyoaki
Published: November 2020

Introduction:
Interstitial fibrosis of myocardium is an important component of cardiac dysfunction. Myofibroblasts, which are activated fibroblasts, contribute to interstitial fibrosis in dilated cardiomyopathy (DCM). Recently, human epididymal body protein 4 (HE4) has attracted attention as a marker specific to myofibroblasts.

Hypothesis:
We hypothesized that the circulating serum HE4 levels were associated with future cardiac events in DCM.

Methods:
We enrolled 44 DCM patients with stable heart failure (HF) condition. Patients with cancer were excluded. We collected blood samples from peripheral vain (PV), ascending aorta (Ao), and coronary sinus (CS) during cardiac catheterization. They were divided into two groups at the median of PV HE4 levels: High PV group (>69 pmol/L); n=22, Low PV group (<69 pmol/L); n=22. Furthermore, they were also divided into groups with median of CS-Ao HE4 levels: High CS-Ao group (>-0.15 pmol/L); n=22, Low CS-Ao group (<-0.15 pmol/L); n=22. Cardiac events were defined as composite of cardiac deaths and hospitalization for worsening HF.

Results:
The mean age, left ventricular ejection fraction (LVEF), and plasma BNP level were 56 years, 32%, and 205 pg/mL. Between two groups, there were no significant differences in age, gender, LVEF, left ventricular end-diastolic diameter, cardiac index, and pulmonary capillary wedge pressure. However, estimated glomerular filtration rate was significantly lower in the High PV group (p=0.025). Survival analysis revealed that the High PV group had a higher rate of cardiac events (
Figure
). However, there was no difference between two CS-Ao groups. As for the pathological analysis, not only the peripheral HE4 level but CS-Ao HE4 level did not significantly correlate with collagen volume fraction in biopsy samples.

Conclusion:
Elevated circulating HE4 is associcated with poor prognosis in ambulatory patients with NIDCM. However, transcardiac gradient of plasma HE4 level might not be associated.
Abstract 14526: The Effect of Radiofrequency Catheter Ablation of Typical Atrial Flutter on Cardiac Chambers' Size and Function
Authors: Jou Stephanie , Goldenthal Isaac L , Biviano Angelo B , Wan Elaine , Saluja Amardeep S , Dizon Jose , Morrow John P , Rubin Geoffrey , Waase Marc , Ehlert Frederick , Liu Qi , Garan Hasan , Yarmohammadi Hirad
Published: November 2020

Introduction:
Cavo-tricuspid isthmus (CTI) dependent atrial flutter (AFL) is one of the most common atrial arrhythmias involving the right atrium (RA) for which radiofrequency catheter ablation has been widely used as a therapy of choice. However, there is limited data on the effect of this intervention on cardiac size and function.

Hypothesis:
CTI dependent ablation for patients with AFL will improve tricuspid valve function, biatrial enlargement, and ventricular function.

Methods:
A retrospective study was conducted on 468 patients who underwent CTI dependent ablation for clinical typical AFL at a single institution between 2010 and 2019. After patients with congenital or rheumatic heart disease, heart transplant recipients, or those without baseline echocardiogram were excluded, 211 patients remained in the analysis. Echocardiographic data were analyzed at baseline prior to ablation, and at early follow-up within 1-year post-ablation. Follow-up echocardiographic data was available for 130 patients.

Results:
Of the 211 patients with CTI-AFL, 200 had typical counterclockwise flutter. The mean age was 64.2±12.1 years old with 12% (n=26) female. The average left ventricular (LV) ejection fraction (EF) significantly improved on follow-up echo (45.55±14.26 to 49±14.4%, p=0.0075), of which 63 (48%) patients had an improvement in EF of 5% or more and 19 (25%) patients had an increased EF of 20% or more. The prevalence of moderate to severe tricuspid regurgitation (TR) was 24% (n=50) at baseline and 18% (n=22) at follow-up with no significant difference (p=0.27). However, 30% (n=39) of the patients had one grade or more improvement in their TR within the 1-year follow-up. Echocardiography also showed improvement of RA size in 48.6%, and left atrial (LA) size in 48.2% of the patients.

Conclusions:
Patients who underwent CTI dependent AFL ablation showed an improvement in cardiac size and function at follow-up evaluation. Although longer-term results are unknown, these findings suggest that restoration of sinus rhythm from atrial flutter is associated with improvement in TR severity, RA size, LA size, and LVEF.
Abstract 14546: Left Ventricular Sphericity Index as a Predictor of Appropriate Implantable Cardioverter-defibrillator Therapy
Authors: Myadam Rahul , D'Souza Jason , Gosch Kensey , Steinhaus Daniel
Published: November 2020

Introduction:
We assessed the hypothesis that markers of LV wall stress, such as LV sphericity index (SI), may predict appropriate therapy for ventricular arrhythmias (VA) in patients with primary prevention defibrillators, independent of LV ejection fraction.

Methods:
We performed a retrospective analysis of consecutive patients with new ICD or CRT-D placement for primary prevention at a single hospital from 01/01/2015 to 06/30/2018. TTE images were used for calculating LV SI, which was defined as the ratio of bi-plane LV end-diastolic volume to the volume of a hypothetical sphere with a diameter of LV end-diastolic length in apical 4-chamber view. Device interrogations were reviewed for appropriate therapy for VA and inappropriate therapy for non-VAs. Kaplan-Meier curves stratified by LV SI tertile were constructed, and Cox proportional hazards models were used to evaluate time to appropriate and inappropriate therapy, and all-cause mortality.

Results:
A total of 282 patients (ICD 154, CRT-D 128) were included. Baseline characteristics are described in the Table. We found a trend towards increased appropriate therapy as LV SI increased in the ICD but not the CRT-D group, but this was non-significant in both (ICD log-rank 0.63, p-value 0.73; CRT-D log-rank 0.07, p-value 0.96). There was no correlation between LV SI and time to all-cause mortality in the ICD (log-rank 0.53, p-value 0.76) or the CRT-D patients (log-rank 0.51, p-value 0.77). LV SI correlated significantly with time to inappropriate therapy in the ICD (log-rank 8.6, p-value 0.01), but not the CRT-D patients (log-rank 2.4, p-value 0.3).

Conclusions:
LV SI demonstrated a non-significant trend towards increased appropriate device therapy in the ICD but not the CRT-D group. LV SI predicted inappropriate therapy in the ICD but not the CRT-D group. Study power was limited by lower than expected event rates, possibly due to changes in device programming and improvements in heart failure therapies over time.
Abstract 14549: Outcome of Radiofrequency Catheter Ablation of Cavo-tricuspid Isthmus Dependent Flutter in Patients With Adult Congenital Heart Disease
Authors: Jou Stephanie , Goldenthal Isaac L , Biviano Angelo B , Wan Elaine , Saluja Amardeep S , Dizon Jose , Morrow John P , Rubin Geoffrey , Waase Marc , Ehlert Frederick , Rosenbaum Marlon S , Garan Hasan , Yarmohammadi Hirad
Published: November 2020

Introduction:
Both typical cavo-tricuspid isthmus (CTI) dependent (or its equivalent) and atypical atrial flutter (AFL) are common in adults with congenital heart disease (CHD) either due to its inherent cardiac anatomy or as a result of prior surgical procedures. Radiofrequency catheter ablation is routinely used as a therapeutic option.

Hypothesis:
Patients with CHD will have an improvement in systemic ventricular ejection fraction and a decreased incidence of atrial arrhythmias after ablation.

Methods:
A retrospective study was conducted on 99 patients with CHD who underwent ablation for clinical AFL at a single institution between 2010 and 2019. Of these patients, 62 had CTI-AFL. The 2 patients with unspecified CHD were excluded. CHD was divided into 3 categories according to the American College of Cardiology Task Force 1 of the 32nd Bethesda Conference - simple, moderate severity, and great complexity lesions. Outcomes of ablation at 1 year follow up were assessed.

Results:
Typical counterclockwise CTI-AFL was seen in 50 patients. The mean age was 49.1±13.6 years old with 29 (48.3%) females. Of the 60 patients, 35% (n=21) had simple lesions, 51.7% (n=31) had moderate lesions, and 13.3% (n=8) had great complexity lesions. The mean left or systemic ventricular ejection fraction (EF) significantly improved on follow-up echo among patients with simple CHD (49.1±13.1 to 56.5±4.7%, p=0.018) and moderate CHD (49.5±14.9 to 54±8.5%, p=0.02), but did not change among patients with great complexity CHD (52.5±6 to 52.5±9.25%, p=0.9). There was a significantly increased incidence of atrial fibrillation (9.5% vs. 16.1% vs. 50%, p=0.04) post ablation among simple, moderate, and great complexity lesions, respectively, but no significant difference in the recurrence rate of atrial flutter (p=0.3).

Conclusions:
Patients who underwent CTI-AFL ablation showed an improvement in EF in patients with simple and moderate CHD. There was also a significantly increased incidence in the development of atrial fibrillation post ablation in CHD with great complexity compared to simple or moderate CHD.
Abstract 14550: Sex Differences on Time-dependent Changes in Brain-type Natriuretic Peptide Among Patients With Hypertrophic Cardiomyopathy
Authors: Enzan Nobuyuki , Matsushima Shouji , Ide Tomomi , Kaku Hidetaka , Tohyama Takeshi , Funakoshi Kouta , Higo Taiki , Tsutsui Hiroyuki
Published: November 2020

Introduction:
Sex differences in biomarkers such as brain-type natriuretic peptide (BNP) have not been fully elucidated among patients with hypertrophic cardiomyopathy (HCM).

Hypothesis:
Sex affects transition of BNP concentration among patients with HCM.

Methods:
This retrospective cohort study analyzed clinical personal record of HCM, a national database of Japanese Ministry of Health, Labor and Welfare, between 2009 and 2014. This record annually collected HCM patient data. Patients with HCM who were assessed with BNP concentration both at baseline and 2-year follow-up were included. Patients were excluded if they received ventricular assist device or heart transplantation during follow-up period. Outcomes were assessed according to sex. The primary endpoint was BNP concentration at 2-year follow-up. The log-transformed BNP concentration at 2-year was analyzed by analysis of covariance adjusted for baseline characteristics including baseline BNP. The cubic spline analysis of BNP concentration at 2-year for sex by BNP concentration was performed.

Results:
Out of 3,570 patients enrolled in the clinical personal record of HCM, 611 patients were included in the present analysis. Mean age was 60.4 years and female and male were 254 (41.6%) and 357 (58.4%), respectively. Left ventricular (LV) ejection fraction was higher in female (64.7 ± 14.5 vs. 61.4 ± 16.0%,
P
=.012), LV diastolic diameter (43.4 ± 7.8 vs. 48.0 ± 8.0 mm,
P
<.001), LV systolic diameter (27.3 ± 8.9 vs. 31.2 ± 9.0 mm,
P
<.001), posterior wall thickness (11.2 ± 3.0 vs. 11.9 ± 3.8 mm,
P
=.011), and left atrial diameter (41.8 ± 8.8 vs. 45.8 ± 10.1 mm,
P
<.001) were smaller in female. Baseline BNP concentration was higher in female (320.3 [159.0-583.1] vs. 182.8 [86.1-363.9],
P
<.001). Female sex was associated with higher log-transformed BNP at 2-year in both complete case analysis (coefficient 0.31; 95% confidence interval [CI] 0.13-0.48;
P
<.001) and multiple imputation analysis (coefficient 0.63: 95% CI 0.44-0.82;
P
<.001). Cubic spline analysis showed that female sex was associated with higher BNP concentration at 2-year irrespective of baseline BNP concentration.

Conclusions:
Female sex was associated with higher BNP levels at 2-year follow-up compared with male sex in HCM.
Abstract 14551: Biomarkers Predicting the Treatment-Resistant Kawasaki Disease
Authors: Yoshikane Yukako , Fukazawa Ryuji , Imanaka-yoshida Kyoko , Kobayashi Naho , Katsube Yasuhiro
Published: November 2020

Introduction:
Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery lesions (CALs). Treatment with a high dose of intravenous immunoglobulin (IVIG), plus steroids if needed, is the most effective therapy for the acute phase of KD. However, there are some very severe cases who need several times additional treatments and are at risk for CALs. In Japan, there are some scoring systems that initially predict IVIG-resistant patients. However, the problem is that these scoring systems fail in multiethnic populations. The aim of this study is to find universal biomarkers that predict treatment-resistant cases of KD.

Methods:
The subject was 276 KD patients, including Group 1 (n=214) who needed only 1
st
line treatment, Group 2 (n=48) who needed 2
nd
line treatment, Group 3 (n=14) who needed 3
rd
line treatment or more. Tenascin C (TN-C), Pentraxin 3 (PTX3) and Procalcitonin (PCT) values, which were selected by systematic review, were measured before initial treatment in each group.

Results:
TN-C; 99.8±41.05 ng/ml in Group 1, 118.0±71.4 ng/ml in Group 2 and 183.0±25.0 ng/ml in Group 3. The TN-C level of Group 3 was significantly higher than that of all the others (p<0.01). The cutoff value for distinguishing Group 3 was 142.0 ng/ml (Area under the Curve (AUC)=0.81). PTX3; 16.2±9.0 ng/ml in Group 1, 31.4±19.7 ng/ml in Group 2 and 58.0±33.0 ng/ml in Group 3. The PTX3 level of Group 3 was significantly higher than that of all the others (p<0.01). The cutoff value for distinguishing Group 3 was 35.1 ng/ml (AUC=0.86). PCT; 0.79±0.77 ng/ml in Group 1, 2.55±3.01 ng/ml in Group 2 and 4.15±4.49 ng/ml in Group 3. The PCT level of Group 3 was significantly higher than that of all the others (p<0.01). The cutoff value for distinguishing Group 3 was 2.55 ng/ml (AUC=0.88). When those three biomarkers combined, Group 3 can be predicted with the sensitivity 79%, the specificity 96%, the positive predictive value 50% and the negative predictive value 99%.

Conclusions:
It may be possible to predict treatment-resistant KD cases with high sensitivity and specificity by combining the measurement from the universal biomarkers, TN-C, PTX3 and PCT, before initial treatment.
Abstract 14553: Mitochondrial Calcium Uptake via Mitochondrial Calcium Uniporter Suppress Ventricular Arrhythmia in the Ischemic Heart Failure Mice
Authors: Hagiwara Hikaru , Watanabe Masaya , Fujioka, Yoichiro , Koya Taro , Nakao Motoki , Takahashi Yumi , Kamada Rui , Ohba Yusuke , Anzai Toshihisa
Published: November 2020

Background:
Delayed after depolarization by calcium (Ca
2+
) leak from sarcoplasmic reticulum (SR) via Ryanodine receptor is one of the causes of ventricular arrhythmias (VAs) in heart failure (HF). Ca
2+
uptake into mitochondria via mitochondrial calcium uniporter (MCU) is participated in Ca
2+
handling, but the relationship between VAs in HF and Ca
2+
uptake into mitochondria is unclear.

Purpose:
We sought to investigate whether increased Ca
2+
uptake into mitochondria via MCU reduces diastolic Ca
2+
leak and suppresses VAs in ischemic HF mice.

Methods:
Ten-week-old male C57BL/6J mice were divided into 2 groups; sham operation mice (Sham) or HF mice (HF) in which myocardial infarction was induced by left coronary artery ligation. After 4-6 weeks, cardiomyocyte or mitochondria were isolated respectively from the myocardium of Sham and the non-infarct myocardium of HF. Ca
2+
waves (CaWs) were measured on an epifluorescence microscopy. Calcium transients and calcium sparks were measured on a confocal microscope in linescan mode. Mitochondrial Ca
2+
uptake were measured by estimating the extra-mitochondrial Ca
2+
reduction with Fluo-5N on a spectrofluoro-photometer. VAs was induced in the Langendorff perfused hearts. Left ventricular (LV) pressure was measured using a
microtip transducer catheter
.

Results:
HF mice showed left ventricular dysfunction and increased heart and lung weights compared to Sham. Kaempferol, a MCU activator, increased mitochondrial Ca
2+
uptake in the isolated mitochondria both in Sham and HF. CaWs and Ca spark frequency in the presence of isoproterenol was attenuated by 10 μM Kaempferol. Kaempferol did not show significant changes in Ca
2+
transient amplitude, however increased the time to 50% decay significantly. The incidence of induced VAs was suppressed by Kaempferol. In vivo measurements, intravenous administration of Kaempferol (5mg/kg) did not show significant changes in hemodynamic parameters in HF mice.

Conclusions:
Ca
2+
uptake into mitochondria via MCU suppresses VAs in HF. Despite the adverse influence of the traditional antiarrhythmic drugs for HF condition, a novel strategy that promotes Ca
2+
uptake into mitochondria might be a potential therapeutic approach for VA treatment in HF patients.
Abstract 14556: Is There a Relationship Between Lipoprotein (a) and Proprotein Convertase Subtilisin /keksin Type 9 and Cardiovascular Events After Acute Myocardial Infarction?
Authors: GALYAVICH Albert , Gimadeeva Alsu
Published: November 2020

Introduction:
Lipoprotein (a) (Lp(a)) has atherogenic effects. Proprotein convertase subtilisin /keksin type 9 (PCSK9) involved in the degradation of LDL-C receptors, increasing LDL-C blood level.

Hypothesis:
Identify the relationship between Lp(a) and PCSK9 blood levels and major cardiovascular events (unstable angina, myocardial infarction, cardiovascular death) after acute myocardial infarction.

Methods:
The study included 119 patients with acute myocardial infarction (97 men and 22 women aged 50-70 years). Blood samples were taken on the 2nd day of myocardial infarction. The Lp(a) blood level was determined by immunoturbidimetry (RANDOX), the PCSK9 blood level was determined by ELISA (BioVendor). Primary combined endpoint included hospitalization due to myocardial infarction and unstable angina and cardiovascular death. Patient follow-up was 52 weeks. Statistical analysis methods included Mann-Whitney test and non-parametric correlation by Spearman.

Results:
In 36 (30.2%) patients with acute myocardial infarction the Lp(a) blood levels were higher than 30 mg/dL. In 83 (69.7%) patients the Lp(a) blood level were below 30 mg/dL. Mean values of Lp(a) blood level was 29.26 ± 2.79 (men 27.71 ± 2.82 mg/dL, women 36.07 ± 8.54 mg/dL, p = 0.797). Mean PCSK9 blood level was 479.7 ± 15.4 ng/ml (males 465.6 ± 16.2ng/ml, females 534.9 ± 38.9 ng/ml, p = 0.122). There was no significant correlation of Lp(a) blood level with total cholesterol, LDL-C, triglycerids and PCSK9 blood levels. No significant correlation was found between Lp(a) and PCSK9 blood levels and cardiovascular events within 12 months. In the group of smoking patients (n = 22) there was found negative correlation between PCSK9 and HDL-C blood levels (-0.45, p = 0.039).

Conclusions:
Due to the fact that there is no relationship between Lp(a) and PCSK9 blood levels and subsequent cardiovascular events within 52 weeks, the effectiveness of the use of PCSK9 inhibitors after acute myocardial infarction is doubtful.
Abstract 14559: Prognostic Utility of Cardiac Markers in Covid-19 Patients
Authors: Damati Ahmad , Chan Kok Hoe Delcos , Farouji Iyad , Al-ramahi Amr , Bhavic Patel , shamoon fayez , Jihad Slim
Published: November 2020

Introduction:
SARS-CoV-2 infection has been associated with a multiple cardiovascular complications. It is not known if cardiac markers can be used for outcome prediction in the US population.

Methods:
We conducted a retrospective study on patients ≥ 18 years old with confirmed COVID 19, who were admitted to our hospital between 03/15/2020 and 05/25/2020. Individuals were included if they had a baseline troponin and brain natriuretic peptide (BNP) available, and if their outcome by the end of the study period was well defined as discharge alive, or deceased. Univariate and multivariate logistic regression methods were employed to identify the cardiac markers associated with mortality in COVID-19 patients.

Results:
The total number of confirmed COVID-19 hospitalized patients during the study period was 348, after excluding patients who did not have cardiac markers available, 233 patients were included in the study, 75 (32%) expired, and 158 (68%) were discharged alive. The median age was 65 years old, and ranged from 22 to 101 years old. 140 males and 93 females. Comorbidities were present in 201 (86%) patients, with hypertension (65%) being the most common, followed by obesity (55%), diabetes mellitus (DM) (44%) and coronary artery disease (27%). Mechanical ventilation was required for 61 patients of whom 42 expired. In univariate analysis, we found a significant difference in history of chronic kidney disease defined by eGFR <45ml/min (p=0.046), DM (p=0.043), initial SOFA (p=0.017), troponin (p=0.001), BNP (p=0.043), CRP (p=<0.0001), LDH (p=<0.0001) and ferritin (p=<0.0001) between survivors and non-survivors. With multivariable logistic regression analysis, the only values that had an odds of survival were a low troponin (odds ratio [OR] 0.17; 95% confidence interval [CI], 0.04-0.52), a low SOFA (OR 0.72, CI 0.50-0.94) and a low CRP (OR 0.87, CI 0.87-0.94).

Conclusions:
This retrospective cohort study of hospitalized patients with COVID-19 suggests an independent association of increased troponin as risk factor for death in COVID-19 patients. Cardiac troponin has been reported as potential prognostic marker in the China cohort. To our knowledge, we are first to demonstrate the utilization of troponin as mortality predictor in the US population.
Abstract 14590: Cardiac Rehabilitation Utilization After Percutaneous Coronary Intervention Remains Exceedingly Low and is Strongly Associated With the Treating Hospital and Operator: Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium
Authors: Sukul Devraj , Seth Milan , Thompson Michael , KETEYIAN Steven J , Boyden Thomas F , Yaser Jessica , Syrjamaki John , Gurm Hitinder S
Published: November 2020

Introduction:
Despite its proven benefits, cardiac rehabilitation (CR) use remains low. Identifying the sources of variation in CR referral and downstream use may help direct policies and quality improvement efforts.

Objectives:
We sought to quantify the magnitude of hospital and operator-level variation in CR referral and utilization after percutaneous coronary intervention (PCI).

Methods:
We used clinical registry data from patients (pts) discharged after PCI between 1/2012 and 10/2016 at 32 Michigan hospitals performing at least 100 PCIs linked to Blue Cross Blue Shield or Medicare claims. Registry and claims data were used to identify (i) CR referral prior to discharge and (ii) any CR use within 90 days after discharge. We calculated hospital-level risk and reliability adjusted rates of CR referral and utilization with Bayesian hierarchical regression models adjusted for patient characteristics and clustering by hospital and operator. Median odds ratios (MORs) with 95% credible intervals (CI) measured variation attributable to hospitals and operators.

Results:
Among 33,593 pts with a valid zip code and discharged home after PCI, 76.4% received an in-hospital referral for CR. Overall CR use was 26.7% and 31.3% among those who received an in-hospital referral. Adjusted rates of CR referral and use across hospitals ranged from 1.0%-100% and 14.9%-73.9%, respectively (Fig). After adjusting for pt factors, there was significant hospital and operator-level variation in CR referral with MORs of 5.91 (95% CI 4.02-9.34) and 1.71 (95% CI 1.60-1.85), respectively. There was also significant hospital and operator-level variation in CR use with MORs of 1.99 (95% CI 1.67 - 2.46) and 1.36 (95% CI 1.29 - 1.44), respectively.

Conclusions:
We found significant hospital and operator-level variation not only in post-PCI CR referral, but also CR utilization. Multi-faceted interventions targeting hospitals and PCI operators are needed to improve CR use after PCI.
Abstract 14597: High Left Ventricular Ejection Fraction and All-cause Mortality in Women With Ischemia: Data From the WISE (Women's Ischemia Syndrome Evaluation)
Authors: Wu Stephanie , Lauzon Marie , Maughan Jenna , Shaw Leslee J , Kelsey Sheryl F , Anderson R David D , Pepine Carl , Bairey Merz C Noel
Published: November 2020

Background:
Relatively high left ventricular ejection fraction (EF) (>65%) was recently associated with higher all-cause mortality in women but not men undergoing noninvasive coronary angiography in the CONFIRM study, although this did not remain significant following adjustment for risk variables and mortality was not adjudicated. We investigated high EF and adjudicated all-cause mortality in the Women’s Ischemia Syndrome Evaluation (WISE) study.

Methods:
The WISE original cohort (enrolled 1996-2000), is a multicenter prospective study of women with suspected ischemic heart disease undergoing clinically indicated coronary angiography. EF was calculated by invasive left ventriculography. We investigated the relationship among high (>65%), normal (55-65%) and low (<55%) EF and adjudicated all-cause mortality using Kaplan Meier and regression analyses.

Results:
Overall 734 women included 298 (41%) high, 355 (48%) normal, and 81 (11%) low EF. The mean age was 58±11 years and mean EF was 65±11% (43%, 63% and 75% in the low, normal and high groups respectively). Over 10 years of follow-up, all-cause mortality occurred in 18% of patients, ranging from 12% in the high EF group to 41% in the low EF group. EF was associated with mortality among groups (
Figure
). Low EF remained a significant predictor of mortality compared to high EF, but normal EF compared to high EF did not in a multivariable regression model. Compared to women in the CONFIRM study, our cohort had higher mean EF (65% v. 62%), higher rates of obstructive CAD and diabetes, and lower rates of hypertension and dyslipidemia.

Conclusions:
Higher EF was not associated with higher all-cause mortality adjudicated predominantly cardiovascular in women with evidence of ischemia. Potential explanations for the lack of concordance with the CONFIRM study may include lack of death adjudication, differences in comorbidities, or other unknown factors.
Abstract 14598: Multiple Arterial Coronary Bypass Grafting is Associated With Improved Survival in Females
Authors: Tam Derrick , Rocha Rodolfo , Fang Jiming , Ouzounian Maral , Chikwe Joanna , Lawton Jennifer S , Ko Dennis T , Austin Peter , Gaudino Mario F , Fremes Stephen E
Published: November 2020

Introduction:
Multiple arterial grafting (MAG) in coronary artery bypass grafting (CABG) is associated with improved survival and freedom from major adverse cardiac and cerebrovascular events (MACCE) in observational studies of mostly males. It is not known whether the MAG is beneficial in females. Herein, we compared the late clinical outcomes of MAG versus single arterial grafting (SAG) in females undergoing CABG for multivessel coronary artery disease (CAD)

Methods:
Clinical and administrative databases for Ontario, Canada, were linked to obtain all female patients with angiographic evidence of left main, triple, or double vessel disease undergoing isolated non-emergent primary CABG from 2008-2019. Baseline characteristics were compared and 1:1 propensity score matching was performed to account for differences. 30-day mortality was compared in the matched groups. Late mortality and MACCE ( composite of stroke, myocardial infarction, repeat revascularization, and death) was compared between the matched groups with a stratified log rank test and Cox-proportional hazard model.

Results:
In total 2,961 and 7,954 females underwent CABG with MAG and SAG respectively for multivessel CAD. Prior to propensity-score matching, compared to SAG, those that underwent MAG were younger (66.0 vs. 68.9 years) and had less comorbidities. After propensity-score matching, 2,446 well-matched pairs were formed. In matched patients, there was no significant difference in 30-day mortality (1.6% vs 1.8%, P=0.43) between MAG and SAG. The median and maximum follow-up was 5.0 and 11.0 years respectively. Over the entire follow-up, MAG was associated with improved survival (Figure, hazard ratio (HR): 0.85, 95% confidence interval (CI): 0.75-0.98) and freedom from MACCE (HR: 0.85, 95%CI: 0.76-0.95).

Conclusions:
MAG was associated with improved survival and freedom from MACCE and should be considered for female patients with good life expectancy requiring CABG.
Abstract 14600: Pre-existing Autoimmune Disease and the Risk for Cardiovascular and Non-cardiovascular Immune Mediated Adverse Events With Immune Checkpoint Inhibitors
Authors: Lee Charlotte , Drobni Zsofia D , Zafar Amna , Alvi Raza M , Murphy Sean P , Mosarla Ramya C , Rambarat Paula K , Hartmann Sarah B , Gilman Hannah K , Zubiri Leyre , Raghu Vineet K , Sullivan Ryan J , Zlotoff Daniel A , Faje Alexander , Reynolds Kerry L , Neilan Tomas G
Published: November 2020

Introduction:
The use of immune checkpoint inhibitors (ICIs) is associated with an increase in cardiovascular events. The mechanism is likely related to immune activation and inflammation. Patients with pre-existing autoimmune disease have a baseline increased risk for cardiovascular disease and have been traditionally excluded from clinical trials of ICIs. There is limited data on the cardiovascular and non-cardiovascular safety of ICIs in these patients.

Methods:
This was a retrospective study of 2845 patients treated with an ICI at the Massachusetts General Hospital. This cohort was screened by individual chart review for patients with a diagnosis of an autoimmune disease prior to ICI therapy. These autoimmune patients were compared to controls at a 1:2 ratio. Baseline characteristics and risk of cardiovascular and non-cardiovascular immune related adverse events (iRAEs) were compared. Cardiovascular events were a composite of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, transient ischemic attack (TIA), deep venous thrombosis (DVT), pulmonary embolism (PE), or myocarditis.

Results:
93 patients had a diagnosis of an autoimmune disease prior to ICI. These patients were more likely to be older and to have a history of coronary artery disease, heart failure, chronic kidney disease, hypertension and diabetes mellitus. There were 12 events over a median follow-up period of 300 days. There was no significant difference in composite of cardiovascular events in follow-up (13 vs. 9.1%, autoimmune vs. none,
P
=0.41). The individual cardiovascular event rates were as follows: MI (4.3 vs. 0.5%,
P
=0.04), PCI (0 vs. 0.5%,
P
=1), CABG (0. vs. 0.5%,
P
=1), stroke (0 vs. 0%), TIA (0 vs. 0.5%,
P
=1), DVT (5.4 vs. 2.2%,
P
=0.17), PE (1.1 vs. 4.8%,
P
=0.17), and myocarditis (2.2 vs. 1.1%,
P
=0.60). There was an increased rate of pneumonitis (14 vs. 4%,
P
<0.001) and skin toxicity (16 vs. 0%,
P
<0.001).

Conclusions:
Patients with pre-existing autoimmune disease treated with an ICI had a higher baseline cardiovascular risk but did not have a significant increase in cardiovascular events in an unadjusted analysis. These patients did, however, have an increased rate of pneumonitis and skin toxicity after ICI.
Abstract 14603: Arterial Vascular Events in Men With Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS)
Authors: Zhang Kathleen W , Fradley Michael G , Addison Daniel , Campbell Courtney , Ghosh Arjun K , Calaway Adam C , Garcia Jorge Alberto , Ponsky Lee , Lenihan Daniel , Desai Nihar R , Weintraub Neal L , Guha Avirup
Published: November 2020

Introduction:
Hormone therapy has been associated with adverse cardiovascular events including arterial vascular events in men with prostate cancer. It is unclear if the risk of arterial vascular events varies by type of hormone therapy used.

Methods:
The Food and Drug Administration’s Adverse Event Reporting System (FAERS) was used to compare arterial vascular event reporting in men receiving hormone therapy from 01/01/2000 to 04/30/2020 for prostate cancer. Therapies evaluated were gonadotrophin-releasing hormone (GnRH) agonists (i.e. leuprolide), GnRH antagonists (i.e. degarelix), androgen receptor (AR) antagonists (i.e. bicalutamide) and abiraterone. Arterial vascular events included coronary artery disease, myocardial infarction, ischemic stroke, peripheral vascular disease, and hypertension requiring hospitalization. Polytomous logistic regression (adjusted for age, need for hospitalization, and event reporting source) was performed for non-GnRH agonists as compared to GnRH agonists.

Results:
Among 34,466 events reported during the study period on single agent therapy, 10.6% were arterial vascular events (5.9% hypertension requiring hospitalization, 2.3% coronary artery disease or myocardial infarction, 2.1% ischemic stroke, and 0.3% peripheral vascular disease). Median age of those with reported arterial vascular events was 76 years (IQR 70 - 82). Arterial vascular events were reported less commonly in men receiving AR antagonists (adjusted reporting odds ratio [ROR] 0.7 [95% CI 0.7-0.8], p<0.0001), abiraterone (ROR 0.9 [0.8-0.98], p=0.02), and GnRH antagonists (ROR 0.9 [0.7-1.1], p=0.15) as compared to those receiving GnRH agonists.

Conclusion:
Arterial vascular events are reported more commonly in men receiving GnRH agonists for prostate cancer as compared with other types of hormone monotherapy. Use of non-GnRH agonists may reduce the risk of adverse cardiovascular events on hormone therapy in men with prostate cancer.
Abstract 14604: Flecainide Induced Myalgias. A Rare but Important Adverse Reaction
Authors: Kumar Dilpat , Muhammad Ebad Rehman , Patel Prashant , Mersfelder Tracey
Published: November 2020

Introduction:
Flecainide is an anti-arrhythmic used in patients with symptomatic arrhythmias without structural heart anomalies. It is known to cause several non-cardiac adverse reactions, most commonly headaches, dizziness, fatigue and nausea. We report a case of symmetric polymyalgia, a rare side effect of flecainide.

Case Report:
A 62 year-old woman with history of atrial fibrillation presented with chest heaviness and generalized myalgias. Just 5 days prior to her presentation, she underwent a cardiac ablation and was started on flecainide 150 mg twice daily. Her other home medications included furosemide, carvedilol, dabigatran, losartan and aspirin, all of which were unchanged. Vital signs were stable. Pertinent exam findings included tenderness to palpation over bilateral calf muscles, muscle strength testing with 3/5 in bilateral flexor and extensor muscles of hip and knee joints, and absent bilateral knee and ankle reflexes. EKG showed normal rate and rhythm. ESR and CRP were elevated with a normal ANA and creatinine kinase. The Naranjo score of 7 suggested a probable cause for flecainide-induced myalgias. Flecainide was discontinued leading to improvement in muscle weakness and reflexes at the time of discharge, and at follow-up visits, her symptoms completely resolved.

Discussion:
Antiarrhythmics are commonly used medications with cardiac and non-cardiac adverse effects. Flecainide-induced adverse effects are dose dependent. In dose ranging studies, increasing flecainide dosages caused significant myalgias, especially in patient taking 300 mg/day. In the appropriate clinical context, healthcare providers should be aware of this rare, reversible adverse effect, to prevent extensive inflammatory or neuromuscular disease workup. As our case illustrates, early discontinuation of flecainide can resolve myalgias and prevent long-term sequelae.
Abstract 14611: Indices of Myocardial Work is an Independent Predictor of Exercise Capacity
Authors: Chen Henry H , Bhat Aditya , Chandrakumar David , Fernandez Fernando , Gan Gary C , Tan Timothy C
Published: November 2020

Introduction:
Exercise capacity has been shown to be an independent determinant of cardiovascular outcomes and prognosis. Conventional measures of left ventricular (LV) diastolic dysfunction, including E/e’ and left atrial (LA) metrics, have been shown to be independent predictors of exercise capacity however little is known about its relationship to myocardial energy utility and expenditure. Myocardial work (MW) is a novel non-invasive modality for assessment of myocardial efficiency and may serve to better define this relationship.

Hypothesis:
Greater wasted myocardial work is associated with reduced exercise capacity.

Methods:
Patients without prior cardiac disease referred to our echocardiography service for stress echocardiograms were prospectively recruited. These patients underwent comprehensive baseline transthoracic echocardiography (TTE) followed by exercise stress echocardiography. Only patients without structural heart disease on TTE and without ischaemia on stress testing were included. Myocardial work was assessed using EchoPac (v2.2, Chicago Illinois). Reduced exercise capacity was defined as METS achieved of ≤7.

Results:
100 consecutive patients meeting inclusion criteria were analysed (45% male, age 56.0±15.7), of which 67% had diabetes and 44% had hypertension. The mean METS achieved was 8.5±3.7. Thirty-nine patients had a poor exercise capacity defined as METS achieved of ≤7. These patients were of older age, had greater indexed LV mass, higher E/e’, larger indexed left atrial volume, greater constructive work, greater wasted work, greater work index and lower work efficiency. On logistics regression, age (p<0.001), and myocardial wasted work (p=0.02) were independent predictors of poor exercise capacity after adjusting for the other clinical and echocardiographic variables.

Conclusions:
Reduced exercise capacity is independently associated with greater wasted work. Larger studies will be required to validate our findings.