bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16353: Effects of Dapagliflozin on Physical and Social Activity Limitations in Patients With Heart Failure and Reduced Ejection Fraction: An Analysis of DAPA-HF
Authors: Docherty Kieran , Kosiborod Mikhail N , Inzucchi Silvio E , Kober Lars , Langkilde Anna Maria , Martinez Felipe A , Bengtsson Olof , Ponikowski Piotr , Sabatine Marc S , SjÃ¶strand Mikaela , Solomon Scott , Jhund Pardeep S , McMurray John J
Published: November 2020

Background:
Patients with heart failure and reduced ejection fraction (HFrEF) suffer limitations in physical and social activities. We examined whether the SGLT2 inhibitor dapagliflozin improved the degree of physical and social activity limitation measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) in DAPA-HF.

Hypothesis:
Dapagliflozin, compared with placebo, would reduce the limitations of physical and social activity experienced by patients with HFrEF.

Methods:
We examined the effect of dapagliflozin on the physical and social limitation domains of the KCCQ at 8 months (prespecified analysis time point). Mean change from baseline was calculated using a linear regression model adjusted for baseline values with no imputation for missing data. Scores range from 0-100, with higher scores indicating better health status.

Findings:
At baseline, 4443 (94%) patients had available KCCQ data. Mean baseline physical limitations and social limitations scores were 66.0±24.0 and 65.5±27.4, respectively. Of the 10 individual domains that constitute these scores, the greatest limitations reported by patients at baseline were in doing gardening or housework or carrying groceries, hurrying/jogging and sexual relationships. Dapagliflozin improved physical and social limitations scores at 8 months (placebo-corrected mean difference +1.88 [95%CI 0.66,3.10] and +1.60 [0.18,3.01], respectively). Each individual domain reflecting physical and social limitations improved with dapagliflozin with the exception of sexual relationships (Table); the greatest improvements were seen in doing gardening or housework or carrying groceries (+2.48 [0.63,4.33]), hobbies and recreational activities (+2.46 [0.75-4.17]), and walking 100yd on level ground (+2.29 [0.62,3.96]).

Interpretation:
In DAPA-HF, dapagliflozin, compared with placebo, improved physical and social limitations as measured by the KCCQ in patients with HFrEF.
Abstract 16361: Effects of Low-dose Triple Combination Therapy on Time at Target Blood Pressure - Results From the TRIUMPH Randomized Controlled Trial
Authors: Gnanenthiran Sonali R , Wang Nelson , Salam Abdul , Webster Ruth , de Silva Asita , Patel Anushka , Rodgers Anthony
Published: November 2020

Introduction:
Cumulative exposure to hypertension is an adverse prognostic marker. However longitudinal assessments of blood pressure (BP), i.e. TIme at TaRgEt (TITRE), are not routinely assessed in practice. Specifically, the effect of low-dose combination anti-hypertensive therapy on TITRE has not been studied.

Hypothesis:
Low-dose triple combination antihypertensive medication achieves greater TITRE compared to usual care.

Methods:
TRIUMPH (TRIple pill vs Usual care Management for Patients with mild-to-moderate Hypertension) was a randomized controlled open-label trial of patients requiring initiation or escalation of antihypertensive therapy. Patients from urban hospital clinics in Sri Lanka were randomised to either once-daily low-dose triple combination polypill (20mg of telmisartan, 2.5mg of amlodipine, and 12.5mg of chlorthalidone) or standard care. This analysis compared TITRE in the intervention and usual care groups over 6 months follow-up, with TITRE defined as percentage of time at target BP. Target BP was defined as <140/90mmHg or <130/80mmHg in patients with diabetes or chronic kidney disease.

Results:
The trial comprised 700 patients (mean [±SD] age: 56±11 years, 58% women). Patients in the triple pill group (n=349) achieved a higher TITRE compared to those in the standard care group (n=351) at 6 months (64±32% vs 43±34%, risk difference -21%, 95%CI -26% to -6%, p<0.001). Almost twice as many patients in the triple pill group spent the majority of follow-up time at target (TITRE >50%: 64% vs 37%, p<0.001). The effect of the triple pill was seen early, with the majority achieving TITRE >50% by 12 weeks. Those on the triple pill achieved a consistently higher TITRE at all follow-up periods compared to usual care (0-6 weeks: 36±31% vs 21±28%; 6-12 weeks: 74±39% vs 46±43%; 12-24 weeks: 77±37% vs 53±44%, all p<0.001). When predictors of TITRE were examined, only triple pill therapy was predictive of TITRE >75% (odds ratio [OR] 3.41, 95%CI 2.30-5.04, p<0.001).

Conclusion:
Among patients with mild-moderate hypertension, treatment with a low-dose triple combination pill significantly increased time at target compared to usual care. This study also introduces TITRE as a novel outcome assessing longitudinal BP control in trials.
Abstract 16365: A New Left Atrial Assist Device for Heart Failure With Preserved Ejection Fraction:
In Vitro
Test
Authors: FUKAMACHI Kiyotaka , Kuban Barry D , Flick Christine , Karimov Jamshid , Horvath David , Miyamoto Takuma , Starling Randall
Published: November 2020

Introduction:
The effective treatment for patients with heart failure with preserved ejection fraction is not yet established. We previously reported the concept of the left atrial assist device (LAAD) that pumps blood from the left atrium to the left ventricle to treat diastolic heart failure (DHF). We have now developed the first working prototype of the LAAD that can be implanted at the mitral valve level (Fig. 1). The purpose of the study was to demonstrate that the LAAD can reduce left atrial pressure (LAP) and increase cardiac output (CO) while maintaining arterial pulsatility and normal aortic valve function in the
in vitro
DHF model.

Methods:
The LAAD was tested at three pump speeds (3,600, 4,400 and 5,200 rpm) on a pulsatile mock loop with a pneumatic pump that simulated the normal function of the native ventricle, as well as mild, moderate, and severe DHF conditions, by adjusting the diastolic drive pressure to limit diastolic filling of the ventricle.

Results:
Without the LAAD, CO and aortic pressure (AoP) decreased dramatically: from 3.9 L/min and 102 mm Hg at normal heart condition to 1.0 L/min and 33 mm Hg at severe DHF, respectively (Fig. 2A, 2B). With LAAD support, both CO and AoP recovered to normal heart values at 4,200 rpm and surpassed normal heart values at 5,200 rpm (Fig. 2A, 2B). With LAAD support, LAP recovered to that of the normal heart condition at 5,200 rpm (Fig. 2C). The pulsatility was maintained (Fig. 2D), as all the CO went through the aortic valve.

Conclusions:
These initial
in vitro
results support our hypothesis that use of the LAAD increases CO and AoP and decreases LAP under DHF conditions, while maintaining arterial pulsatility and full function of the aortic valve.
Abstract 16368: Establishment of Administration Protocol of Immunosuppressive Drug for Ips Cell Derived Cardiomyocytes Patch Transplantation in Rat Myocardial Infarction Model
Authors: Ito Emiko , Miyagawa Shigeru , Kawamura Ai , Takeda Maki , Kawamura Takuji , Harada Akima , Oyama Kenji , Mochizuki-oda Noriko , Sawa Yoshiki
Published: November 2020

Background:
Although Cardiomyogenesis therapy using iPS cells for heart failure should overcome immune rejection because of allogenic cell source, appropriate protocol of immunosuppressant to promise efficacy and safety has not been fully elucidated. In this study, we investigated the duration of immunosuppressant administration that could promise the efficacy of human iPS cell derived cardiomyocytes (hiPSCs-CM) patch transplantation as well as safety.

Methods:
The hiPSCs-CM patch were transplanted to myocardial infarction model rats with normal immune function in immunosuppressant treatment groups. Control were underwent sham operation and treated with no immunosuppressant (Group1). Immunosuppressant treatment groups were divided into three groups as follows: treated with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisolone (PSL) for 1month and 1 month tapering period (Group2); treated with TAC, MMF, and PSL for 2month and 1 month tapering period (Group3); and treated with TAC, MMF, and PSL for 3month and 1 month tapering period (Group4). After 6 months, cardiac function and histology were analyzed.

Results:
hiPSC-CM patch transplantation showed significant improvement cardiac fraction compared to the Group1 (ΔLVEF; Group2 22 ± 3 %, Group3 28 ± 5 %, Group4 23 ± 4 % versus Group1 -15 ± 8 %,
P
< 0.05) and did not show any differences in immunosuppressant treated groups. The hiPSCs-CM patch were detected for 2 months post-transplant and Improved Cardiac functions were maintained for at least 6 months despite disappearance of the transplanted patch. Fibrosis and cardiomyocyte size were significantly ameliorated in Group2-4 compared with Group1, however, there were significant differences in immunosuppressant treated groups. Furthermore, the Group 2, 3 and 4 showed a greater amount of structurally mature blood vessels compared with Group1, however, there were no significant in immunosuppressant treated groups. Tumor formation was not observed 6 months after transplantation in the Group 2, 3 and 4.

Conclusion:
2 months administration of immunosuppressive agent may promise the safety and efficacy of hiPSCs-CM patch transplantation for rat ischemic heart failure model, proposing appropriate recipe of immunosuppressant in clinical trial.
Abstract 16386: Patient Perceptions of Cardiac Electrophysiology Procedural Postponement at an Urban Center During the SARS-CoV-2 Pandemic
Authors: Lacharite Roberge Anne Sophie , Haddad Abdullah , Khazan Benjamin , Noto Joseph , Tragesser Lauren , Garber Rebecca , Gangireddy Chethan , Cronin Edmond , Basil Anuj , Yesenosky George , Greenberg Richard , Vaidya Anjali , Brisco-Bacik Meredith , Cooper Joshua M , Whitman Isaac
Published: November 2020

Background:
To curb transmission of SARS-CoV-2 and to preserve hospital resources, elective procedures were indefinitely postponed nationally, affecting many patients previously scheduled for electrophysiology (EP) procedures. Procedural wait times may affect patient satisfaction and retention, yet patient perceptions of procedural postponements during the SARS-CoV-2 pandemic are currently unknown.

Methods:
We performed a phone survey of consecutive patients who experienced EP procedural postponement from March – April 2020. Surveys were performed between May 1 – May 15. Sociodemographics, SARS-CoV-2 testing history, notification circumstances, and perceptions were obtained from patients.

Results:
Of 112 patients postponed, 77 patients consented to the survey, most of whom were minorities (black 43%, Hispanic 20%), 30% were below the poverty line, and 67% had ≤ high school education. Catheter ablation accounted for 33% of procedures and device procedure 44%. Half of patients (51%) were informed of their postponement by their electrophysiologist. In response to when patients thought their procedure would occur, 37% believed it would occur within 12 weeks of the survey. Perceptions and testing history are shown (
Figure
). Patients who had undergone SARS-CoV-2 testing were more likely to disagree with postponement than those who had not undergone testing (30% of those tested disagreed vs. 2% of those not tested, p<0.001). Only 1 of 7 patients who had their procedures done in the interim had it done at another institution. Of the 11% of patients reconsidering their procedure, 22% were AF patients and 45% were heart failure patients.

Conclusion:
Within an urban population, most patients agreed with procedural postponement and felt their procedure would occur soon. Interim SARS-CoV-2 testing was associated with disagreement with postponement and one third of patients had high anxiety about postponement. In our experience, patient retention was high.
Abstract 16388: Feature Selection Using Recursive Feature Elimination (RFE): Machine Learning Application in Predicting Permanent Pacemaker Implantation (PPMI) in Patients Undergoing Transcatheter Aortic Valve Replacement (TAVR)
Authors: Ilyas Suleman , Sheikh Wasiq , Parulkar Anshul , Ahmed Malik B , Ovide Gerry , Rosen Benjamin , Osler Brian , Lima Fabio V , Sharma Esseim , Chu Anthony
Published: November 2020

Introduction:
TAVR is increasingly being performed because of several recent large-scale clinical trials supporting its use across a range of patient sub-classes. Although it provides life-altering relief of severe aortic stenosis, adverse outcomes are not uncommon including paravalvular leak, life-threatening bleeding, acute kidney injury, stroke, and PPMI. RFE can help certain classification models like logistic regression in better predicting binary variables such as PPMI by creating a model based upon a set of predictors and then progressively eliminating variables to optimize the model.

Objective:
To determine whether RFE when applied to logistic regression would result in discriminatory ability in the prediction of PPM implantation in patients undergoing TAVR

Methods:
Pre- and postoperative data from a single institution were collected for all patients undergoing TAVR without a history of PPMI between January 2016 and December 2019. EKG data obtained included QRS duration, presence of atrioventricular block, left anterior and posterior fasicular block and right bundle branch block(RBBB). Data was imported into Python and a stratified 5 fold cross validation with SMOTE oversampling was run with RFE running at every fold to avoid overfitting. Upon completion, a rank score was tabulated for each predictor and a final logistic regression model with the highest optimized receiver under the operator curve was exported and applied to a test set. The receiver under the operator score was calculated for the training and test sets and the variables of importance were identified using RFE.

Results:
The total sample size for this cohort was 513 patients, with a PPMI incidence of 8.58%. The training set consisted of 40 variables and 384 patients, and the test set had 129 patients. The final optimized model on the training set had an ROC of 0.75 and utilized three features out of forty. The three features identified by RFE were: implanted TAVR valve size, QRS duration, and presence of RBBB. The model had a ROC of 0.63 on the test set.

Conclusions:
Our results show that presence of pre-op RBBB, prolonged QRS duration and valve size were risk factors for PPMI. Logistic regression classification had modest ability in predicting the need for PPMI after TAVR.
Abstract 16720: Cardiovascular Toxicities of Cyclin Dependent Kinase (cdk) 4/6 Inhibitors in Metastatic Breast Cancer Patients
Authors: Fradley Michael G , Nguyen Nam , Chen Yiqing , Guha Avirup , Upshaw Jenica N , Ky Bonnie , Gong Yan
Published: November 2020

Introduction:
Cyclin Dependent Kinase (CDK) 4/6 inhibitors are a novel class of cancer therapeutics which have significantly improved survival in patients with hormone receptor positive, HER2 negative metastatic breast cancer. There is little data regarding the epidemiology of cardiotoxicity with these therapies.

Methods:
Using the OneFlorida Data Trust
,
adult patients without prior cardiovascular disease who received at least one CDK 4/6 inhibitor between January 1, 2012 and December 31, 2018 were included in the analysis. CAEs identified from ICD 9/10 codes include: new hypertension (HTN); arrhythmias (excluding sudden cardiac death); new hypertension (HTN); heart failure/cardiomyopathy; ischemic heart disease, pericardial disease. Log-rank tests were performed to compare time to all-cause mortality in patients with or without CAE. Multivariable cox proportional hazard regressions were performed to estimate the hazard ratio (HR) and 95% confidence interval (CI) for mortality adjusting for age, gender, race, obesity, HTN, diabetes (DM) and hyperlipidemia (HLD).

Results:
A total of 1,035, predominantly female (96%) patients were included in the analysis. The mean age was 61±13 years, and CV risk factors were prevalent at baseline: obesity (17.1%), HTN (22.2%), DM (9.9%), HLD (10.5%). Cardiotoxicity occurred in 174 (16.8%) patients of which 30 (17.2%) died (p<0.001). There were 61 cases of arrhythmias with 15 (24.6%) deaths (p<0.001) and 97 cases of new HTN with 15 (15.5%) deaths (p<0.001). Unadjusted and adjusted HRs and 95% CIs for mortality are shown in the figure. Effects were similar across all CDK 4/6 inhibitors.

Conclusions:
Cardiotoxicity is common with CDK 4/6 inhibitors and are associated with overall increased mortality and arrhythmias and HTN accounting for a significant proportion of this finding. Patients taking CDK 4/6 inhibitors should be monitored for CAEs with aggressive risk mitigation strategies to minimize morbidity and mortality.
Abstract 16725: Predicting the Need for a Permanent Pacemaker Device Following Transcatheter Aortic Valve Replacement Using Supervised Machine Learning
Authors: Sheikh Wasiq , Parulkar Anshul , Ahmed Malik B , Ilyas Suleman , Sharma Esseim , Lima Fabio V , Rosen Benjamin , Osler Brian , Ovide Gerry , Chu Antony F
Published: November 2020

Introduction:
TAVR is approved for use for a range of patients with aortic stenosis. The need for a permanent pacemaker device (PPD) after TAVR varies, but can range from 2 to 51%. Risk factors for requiring PPD after TAVR appear to include being male and having baseline conduction disturbances. Being able to predict who may require PPD could identify at risk patients early and may confer cost savings. Given the advent of machine learning classifier techniques, random forests may aid in better predicting need for PPD after TAVR by using pre-operative variables.

Hypothesis:
Random Forests offer discriminatory ability in predicting the need for PPD after TAVR using primarily pre-operative variables.

Methods:
Pre-operative data from a single institution were collected patients undergoing TAVR without a history of PPD between January 2016 and December 2019. EKG data was obtained including underlying rhythm, QRS duration and any underlying conduction abnormality. Other variables included anti-arrhythmic data, comorbidities, and eGFR. Data was imported into Python and a stratified 5 fold cross validation with SMOTE oversampling running at every fold to avoid overfitting was run on the training set. The model that optimized the receiver under the operator curve was exported and applied to a test data set. Precision and recall were calculated to assess classification.

Results:
A total of 513 patients were identified with nearly 9% eventually requiring PPD. A total of 40 predictor variables were utilized in the modeling. A stratified split of the data resulted in a training set of 384 patients and a test set of 129 patients. A total of 500 trees were used on the training set. The final optimized model had an ROC of 0.71 with the following parameters: gini criterion, max depth of 4, and logarithm max features . When applied to the test set, the model had an ROC of 0.63. Overall accuracy was 0.78, with a precision and recall for no PPD after TAVR being 0.94 and 0.81 and a precision and recall for PPD after TAVR of 0.18 and 0.45.

Conclusions:
Our results show that machine learning techniques, specifically random forests have discriminatory ability in predicting PPD after TAVR. More tuning of the models are required to achieve better discrimination.
Abstract 16741: A Comparison of High versus Conventional Power Radiofrequency Catheter Ablation for Pulmonary Vein Isolation: A Systematic Review and Meta-Analysis
Authors: Amin Mustapha , Nayfeh Tarek , Nanaa Ahmad , Mohir Saadi Samer , Killu Ammar M , Madhavan Malini , Kapa Suraj , Desimone Christopher V , Mulpuru Siva K , Deshmukh Abhishek
Published: November 2020

Objectives:
We sought to evaluate the procedural safety and outcomes of high power (HP) versus conventional power (CP) radiofrequency (RF) ablation during pulmonary vein isolation (PVI).

Methods:
A systematic search was used via MEDLINE, EMBASE, and Cochrane databases between 01/1998 and 05/2020 for studies comparing the safety and efficacy between HP and CP during RF ablation for PVI using contact-force catheters (ThermocoolSmartTouch or TactiCath). The search terms used were “AF” AND “catheter ablation” OR “radiofrequency ablation”.

Results:
From eight comparative observational studies, we developed a cohort of 992 patients (478 in the HP and 514 in the CP group). The median maximum energy output used in the HP group was 50W vs 35W in the CP group. There was a statistically significant difference noted in acute pulmonary vein reconnection (APVR) in the HP group compared to the CP groups at16% vs 32.6%, respectively (RR: 0.53, 95% CI: 0.33 - 0.86, P = 0.01). Freedom from arrhythmia at 12 months follow-up was also significant and found to be 87.8% of cases in the HP group versus75.2% of cases in the CP group (RR: 0.46, 95%CI: 0.32 - 0.65, P <0.01). The mean RF ablation time was 20.1 minutes in the HP group vs 39.6 minutes in the CP group (P <0.01). The mean total procedural time was 103.5 minutes in the HP group compared to 135 minutes in the CP group (P <0.01). Two patients in the CP group experienced severe adverse events (1 cardiac tamponade and 1 myocardial infarction). No serious AEs were found in the HP group. Non-serious AEs (groin complications, pericardial effusion, and phrenic nerve injury) were reported in 0.35% and 0.51% of cases in the HP and CP group, respectively.

Conclusion:
This study suggests that HP PVI ablation can be associated with better ablation outcomes by reducing the rate of acute and late PV reconnection and atrial arrhythmia recurrence, with similar safety profiles, and shorter procedural times. These findings merit evaluation in a randomized controlled trial.
Abstract 16748: Stent Type and Outcomes in Patients With Malignancy Undergoing Percutaneous Coronary Intervention
Authors: Munawar Muhammad Mohsin , Awan Ahmad A , Ogunti Richard , Fatima Urooj , Ahmad basharat , Opoku issac
Published: November 2020

Background:
Coronary artery disease and cancer share some of the same risk factors, so it is not uncommon to find them in same patient. So PCI is increasingly performed in these patients. However type of stent and its impact on mortality is largely unknown.

Methods:
Nationwide Inpatient Sample (HCUP-NIS) database was utilized to identify patient who have underwent BMS or DES placement and had active cancer. Appropriate ICD 9 codes was used to identify lung, colon, breast, prostrate, hematological, liver, brain and kidney cancer as well as metastatic cancer. Patient were randomly assigned in 1:1 ratio to BMS and DES group. Propensity score analysis was performed using neighborhood matching to baseline co-variates and reduce confounding bias. Percentage of patients getting BMS and DES were analyzed and compared to general population. While comparing DES and BMS group, outcomes included in-hospital mortality, stent thrombosis, length of stay, acute kidney injury and bleeding complications.R
esults:
A total of 8755 patients were selected in BMS group and 11,611 patients were selected in DES group. Following propensity matching, 4313 patients were selected in both groups and randomly assigned 1:1 ratio to BMS and DES. As compared to general population (BMS 23.2%, DES 76.8%), there is high use of BMS stent in cancer patient (BMS 43.0%, DES 57.2%). When comparing BMS to DES group, there is no statistically significant difference in mortality (4.7 vs 3.8 percent p=0.097), acute kidney injury (11.3 in BMS vs 10.6 in DES p = 0.425), bleeding complications (3.50 in BMS vs 3.45 in DES p = 0.914) and length of stay (5.4 in BMS vs 5.2 in DES p = 0.119). There is increased incidence of stent thrombosis in DES group (4.26% vs 3.01%, p-value 0.02). Among the cancers, adjusted for type of stent placed, liver and pancreatic cancer was associated with significant increase in stent thrombosis

Conclusion:
In patients with active malignancy, there is higher incidence of BMS placement as compared to general population. There is high incidence of stent thrombosis is DES without increase in mortality. Among the cancers, adjusted for type of stent placed, liver and pancreatic cancer was associated with significant increase in stent thrombosis
Abstract 16753: Baseline Prediction of Atrial Fibrillation Recurrence After Catheter Ablation: Comparative Analysis of Prognostic Models Using Data Recorded by Implanted Cardiac Monitors
Authors: Tang Lisa YW , Ho Kendall , Hawkins Nathaniel , Tam Roger , Lim Michael , Andrade Jason
Published: November 2020

Intro:
Tools for baseline prediction of catheter ablation outcome are instrumental to treatment management that best balances positive outcomes against risk of treatment complications. To date, many such predictive models exist in the literature; yet, it is unclear which should be adopted as no study has compared all using a single dataset.

Goals:
examine 8 published models using a single dataset with expert-annotated data recorded by implanted monitors.

Methods:
We collected data from a cohort of ~350, acquired from a randomized clinical trial blinded to ablation outcome. Based on a 2020 review, we shortlisted 12 models for baseline prediction of recurrences recorded between days 91-365 post ablation per standard. Models that use postoperative data, thus unsuited for baseline prediction, were excluded. Four models were further dropped from this work as their required variables (e.g. normalized atrial area) are unavailable in our cohort.

Results:
There was no missing variable; 34% were female and 53% of patients experienced recurrence. Figure reports each model’s performance with metrics as sensitivity (SEN), specificity (SPEC), positive predictive value (PPV), negative predictive value (NPV), area under receiver operating characteristic curve (AUC), positive and negative clinical utility indices (SENxPPV; SPECxNPV, resp.). The digit after each model name indicates the cut-off used (some studies used different cut-offs). Models are presented in rank-order by utility indices. All evaluated scores achieved AUC<65 and deemed to have poor utility. A model that examines age, stroke, hypertension, heart failure, chronic obstructive pulmonary disease, and obstructive sleep apnea, performed best in this cohort (SEN=54, SPEC=70,PPV=65,NPV=60,AUC=62).

Conclusions:
Our results reinforce statements of previous reviews that many published models are lacking and that there remains a need to develop and validate models for prediction of AFR post ablation.
Abstract 16755: Personalized Virtual Cardiac Resynchronization Therapy Simulation Based on a 12-Lead ECG and CMR Predicts Electrical Activation Changes After Cardiac Resynchronization Therapy
Authors: Bilchick Kenneth C , Lluch Eric , Oomen Pim , Gao Xu , Holmes Jeffrey W , Kramer Christopher M , Mansi Tommaso
Published: November 2020

Introduction:
Simulating electrical remodeling after cardiac resynchronization therapy (CRT) based on individual patient characteristics could enhance the effectiveness of the procedure, help select optimal CRT candidates, and yield important prognostic data.

Hypothesis:
A Virtual CRT (V-CRT) simulation based on the 12-lead ECG and cardiac magnetic resonance (CMR) for evaluation of biventricular structure and extent of scar with late gadolinium enhancement (LGE) would predict changes in electrical activation after CRT.

Methods:
V-CRT uses cardiac geometry and scar (LGE) from CMR, a torso avatar from CMR scouts, and an electrophysiology model derived from the baseline ECG, the left ventricular (LV) pacing site, and programmed CRT pacing parameters. Ventricular activation times and the resulting QRS duration (QRSd) after CRT were estimated. The predicted QRS durations were then compared with the actual QRS durations after CRT pacing.

Results:
20 CRT patients (age 67.3 ± 10.2 years, 30% female, 50% with LV scar) had a mean pre-CRT QRSd of 151 ± 12.8 ms. This predicted post-CRT QRSd depended significantly on the LV pacing site with a median maximum-minimum difference per patient over all possible pacing sites of 39.8 ms (IQR 32.5-44.2 ms). The post-CRT QRSd predicted by V-CRT based on the actual LV pacing site correlated well with the observed post-CRT QRS duration (r=0.51, p=0.02) (Figure). Predicted changes in the QRS duration were strongly associated with changes in LV activation times (r=0.74, p=0.0002), but not RV activation times (no correlation). Greater predicted reductions in LV activation times were more common in patients with greater LV end-diastolic volume indices (LVEDVIs) by CMR (r=-0.58, p=0.01).

Conclusions:
V-CRT effectively predicts changes in electrical activation after CRT. These findings have important implications for patient selection for CRT, prognosis after CRT, and CRT implementation strategies.
Abstract 16760: Comparing Major Complications Between Radiofrequency and Cryoballoon Ablation: A Systematic Review and Meta-Analysis
Authors: Drame Awa , Rodriguez Daniel , Kotch Nicholas , Cassidy Dennis , Wilson David , Lu Yuanyuan , Herweg Bengt , Chae Sanders H
Published: November 2020

Introduction:
Catheter ablation has become the cornerstone for the treatment of drug-refractory paroxysmal atrial fibrillation. Two main forms of energy are used: cryoablation (CB) and radiofrequency (RF). Multiple studies have compared the effectiveness/safety curve between these two; among which is the FIRE AND ICE and the FREEZE AF trials which showed non-inferiority between these two technologies. Despite the remarkable success achieved at controlling arrythmias, complications as high as 16.3% have been reported in both technologies.

Objectives:
The main purpose of this meta-analysis is to compare the incidence of esophageal and myocardial injuries among patients undergoing radiofrequency ablation vs cryoablation for the treatment of atrial fibrillation or atrial flutter (AF).

Methods/Results:
We searched Pubmed/Embase, Medline and Cochrane from inception to April 2020 for studies that met our predetermined inclusion and exclusion criteria. All studies comparing RFA to CBA and reporting the incidence of life-threatening complications (esophageal injuries and perforation/tamponade) were included in our analysis. To limit confounding variables and significant heterogeneity between studies, we selected only randomized-control trials and propensity-matched observational studies. A total of 2748 patients were identified. Overall analyses show that RFA has significantly higher life-threatening complications than CBA (OR = 2.79, 95% CI: 1.41-5.52; p=0.003).

Conclusion:
The present systematic review and meta-analysis demonstrates that RFA has 3 times more life-threatening complications than CBA. As previous studies have already shown similar degree of freedom from AF between these two ablation technologies, CBA appears to be more advantageous overall.
Abstract 16761: Refining Individualized Risk Prediction for Apparent Treatment-Resistant Hypertension in a Large Multiethnic Biobank: The Million Veteran Program
Authors: Akwo Elvis A , Chen HuaChang , Rowan Bryce X , Robinson Cohen Cassianne , Chung Cecilia P , Ikizler Talat A , Sun Yan , Wilson Peter W , Tsao Philip S , O'Donnell Christopher J , Edwards Todd L , Kovesdy Csaba , Tao Ran , Hung Adriana M
Published: November 2020

Introduction:
Approximately 10-20% of treated hypertensive patients have apparent treatment-resistant hypertension (ATRH), which is associated with adverse cardiovascular outcomes. Our goal was to develop a prediction model for ATRH that combines clinical data and a genetic risk score (GRS) for ATRH.

Methods:
Study participants were 232,925 patients with hypertension (HTN) enrolled in the Million Veteran Program receiving care at the VA from 2004 to 2017. 21% were black and 6% were women. Incident ATRH was defined as failure to achieve outpatient blood pressure (BP) <140/90 mmHg with 3 anti-HTN drugs including a thiazide or the use of ≥4 drugs. In the training data (n = 207,375), a logistic regression model was fit with age, sex, race, smoking history, body mass index, diabetes, anti-HTN drug classes, baseline systolic BP (SBP), diastolic BP, eGFR, serum potassium, serum bicarbonate and serum lipids. A weighted GRS was developed in the training data using 21 significant SNPs from a transethnic ATRH GWAS. An independent test data (n = 25,550) was used to validate the clinical model and fit a GRS-enriched (clinical model + GRS) model.

Results:
Over a 13.5-year follow-up, 20,536 and 2,247 incident ATRH cases were observed in the training and test data. In the training data, the clinical model had reasonable discriminant ability (C=0.706) and good calibration (Brier score = 0.085). Age, diabetes, and SBP were the strongest predictors of ATRH. In the test dataset, a 1-IQR increase in the GRS was associated with a 10% (95%CI: 1.04-1.17) higher odds of ATRH. In the test dataset, the LR χ
2
, C-statistic and Brier score for the clinical model were 1075, 0.705 and 0.077 respectively. In the GRS-enriched model, these values were 1107, 0.708 and 0.077. The net reclassification improvement was 1.5% (95% CI: 0.3-2.8, p=0.02). The GRS-enriched model had excellent calibration with an optimism-corrected calibration slope of 0.95.

Conclusion:
Augmenting a clinical prediction model for ATRH with a GRS comprising GWAS-significant SNPs improved model fit but not discriminant ability. Future work will evaluate whether models incorporating polygenic risk scores with a larger number of variants may refine ATRH risk prediction and stratification and evaluate race-specific performance.
Abstract 16766: Intraprocedural Ablation and Fluid Status Management in Heart Failure Patients Undergoing Catheter Ablation for Atrial Fibrillation
Authors: Allam Sahitya , Harmon Evan , Mazimba Sula , Mangrum James M , Kutinsky Ilana , Haines David , Mehta Nishaki K
Published: November 2020

Background:
Recent randomized clinical trial data has supported catheter ablation (CA) of atrial fibrillation (AF) in patients with heart failure (HF). Ablation and fluid management strategies could impact periprocedural outcomes especially in HF patients.

Methods:
We conducted a single-center retrospective analysis of 200 consecutive patients with and without HF undergoing CA at a tertiary care academic center from July 2017 through June 2018. HF was defined as any EF < 40%, prior inpatient admission for HF exacerbation, or ambulatory management of HF confirmed by independent chart review. Diuretic regimens were reported as furosemide equivalent.

Results:
Among 200 patients, 65 (32.5%) had HF and 135 (67.5%) did not. HF patients had longer mean procedure times (299.8 ± 96 min vs 268.4 ± 96 min, p = 0.03) and were more likely to require mitral isthmus (p < 0.001), posterior wall isolation (p = 0.002), and cavotriscupid isthmus (p = 0.004) ablations. There were no differences between the HF vs. non-HF groups’ intraprocedural volume intake, intraprocedural volume output, net fluid status, or intraprocedural diuretic dose (Table 1). HF patients received higher doses of IV (41.5 ± 43.0 mg vs 23.6 ± 11.8 mg, p = 0.007) and PO (43.2 ± 16.7 mg vs 26.7 ± 10.0 mg, p < 0.001) postprocedural diuretic. There were no differences in the rates of major in-hospital complications (Table 1). In a multivariable regression analysis adjusted for procedural covariates, there were higher proportions of posterior wall isolation (p = 0.01) as well as postprocedural PO (p = 0.01) and IV diuretic (p = 0.002) administration in the HF cohort.

Conclusion:
Intraprocedural volume and diuretic management was similar between HF and non-HF patients undergoing CA of AF, though HF patients tended to receive more aggressive diuresis post procedurally with no difference in complications.

Table 1.

Intra- and post-procedural management and outcomes in HF vs non-HF patients undergoing CA for AF
Abstract 16785: Student Abstractors Reduce the Cost of Registry Use Without Compromising Quality
Authors: Lakkis Nasser , Capetillo Allison P , Boxberger Cherie S , Chapman Stephanie
Published: November 2020

Introduction:
Accurate data abstraction is the cornerstone of successful implementation of Get With The Guidelines-Heart Failure, but abstraction costs are the single largest barrier to participation.

Objective:
The Heart Failure Abstraction Internship was established to test the efficacy of part-time, graduate students as GWTG-HF abstractors in comparison to a registered nurse using an acceptable Data Element Agreement Rate (DEAR).

Methods:
The selection criteria for the pilot hospital, Ben Taub Hospital, Houston Texas was: not a GWTG-HF participant; serving diverse populations; administrative and physician support and available supervision for interns. Intern abstractors were recruited and paid as American Heart Association (AHA) employees. For the pilot term, the interns were onboarded as volunteers for the pilot hospital. They met the onboarding requirements of AHA and the pilot institution’s requirements for hospital volunteers. The interns; worked on-site at the pilot institution; were given computer access to EPIC electronic medical records and GWTG-HF; were trained by AHA Quality staff and the pilot hospital Cardiology Program Manager; and abstracted all patients with a primary diagnosis of heart failure from October 2017 to December 2018. An AHA nurse auditor virtually re-abstracted 5 records with the pilot, Cardiology Program Manager. The audit was conducted using the July 2018 Clinical Registry Form (CRF) that was also used during the pilot.

Results:
The intern abstractors matched the re-abstractor at a DEAR of 86.4% with 340 total elements and 46 mismatches.

Conclusions:
The hypothesis was proven with a DEAR of 86.4%, suggesting hospitals can be successful participants in GWTG utilizing student abstractors for data collection needs. The median payrate for a nurse abstractor is $24.50 per hour, not including benefits*. The rate for part time employment for the abstraction interns was $10.00 per hour. In addition to financial savings for the pilot organization, the interns worked efficiently as they focused on one task allowing the clinical team to focus on process improvement based on the data collected. This PI focus led to other outcome improvements including reduced readmission and increased compliance with GDMT.

*Payscale.com
Abstract 16787: Calcium Channel Blockers and Nitrates in 5-FU Vasospasm
Authors: Zafar Amna , Drobni Zsofia , Alvi Raza , Lei Matthew , Lou Uvette , Mosarla Ramya , Murphy Sean , Jones-O'Connor Maeve , mahmood ali , Hartmann Sarah , Gilman Hannah K , Weekes Colin D , Nipp Ryan , Clark John R , Clark Jeffrey W , Blaszkowsky Lawrence , Tavares Erica , Neilan Tomas G
Published: November 2020

Introduction:
Coronary vasospasm is a side effect of 5-FU (fluorouracil). Beyond switching chemotherapy regimens, there are no established treatments for vasospasm. Limited data exist regarding the efficacy of calcium channel blockers (CCBs) and/or nitrates with 5-FU vasospasm.

Methods:
We conducted a retrospective analysis of all patients at Massachusetts General Hospital who were diagnosed with 5-FU coronary vasospasm. As part of institutional practice, those referred to cardio-oncology receive pre-treatment with vasospasm therapies (either combination [nitrates and CCBs] or single agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcomes were the safety and effectiveness of this cardiac pre-treatment approach.

Results:
Among 7,711 patients who received 5-FU from Jan 2001 to Jul 2017, 86 (1.11%) developed coronary vasospasm. Overall 64 patients continued to receive subsequent 5-FU, while 22 stopped. Of the 64 who continued, 60 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU. Of these 60, 52% (31/60) received both nitrates and CCBs, 20% (12/60) received CCBs alone, and 28% (17/60) received nitrates alone, while 4 continued 5-FU without cardiac pre-treatment. Chest pain (without a myocardial infarct) recurred in 11.7% (7/60) among those who received cardiac pre-treatment vs. 50% (2/4) among those who did not (P=0.033). When those who stopped were compared to those who continued 5-FU (with cardiac pre-treatment), the cardiovascular profile, stage and type of cancer were similar. As compared to patients who stopped 5-FU, those who continued after nitrates/CCBs had improved progression free (HR 0.56, P=0.076 [95% CI 0.30-1.06]) and overall (HR 0.29, P<0.001 [95% CI 0.15-0.57]) survival.

Conclusion:
In the largest report of 5-FU associated vasospasm, re-challenge after pre-treatment with CCBs and nitrates was safe and effective, thus allowing patients to receive additional 5-FU.
Abstract 16793: Smad7 Induction in Activated Infarct Myofibroblasts Protects From Adverse Remodeling by Restraining TGF-beta-Mediated and Receptor Tyrosine Kinase Signaling
Authors: Humeres Claudio D , Shinde Arti V , Hanna Anis , Conway Simon , Frangogiannis Nikolaos G
Published: November 2020

Cardiac repair is dependent on myofibroblast TGF-b/Smad3 signaling and subsequent formation of an organized scar. However, to prevent prolonged activation and fibrosis, TGFβ effects are tightly regulated through induction of suppressive signals, such as the inhibitory Smads, that restrain TGFβ cascades. We hypothesized that the inhibitory Smad7 may be induced in infarct myofibroblasts, protecting from adverse remodeling and fibrosis. Moreover, we dissected the molecular signals modulated by Smad7. Smad7 is markedly induced in infarct myofibroblasts through a TGFβ/Smad3 pathway. To investigate the role of endogenous Smad7 in post-infarction remodeling, we generated mice with myofibroblast-specific Smad7 loss (MFS7KO). Following non-reperfused infarction, MFS7KO mice had increased late mortality that was not due to rupture, but was associated with worse heart failure. Surviving MFS7KO mice had accentuated adverse remodeling, worse systolic/diastolic dysfunction and increased collagen deposition in the infarct border zone, in comparison to Smad7 fl/fl animals. In isolated cardiac fibroblasts, Smad7 overexpression attenuated myofibroblast conversion and profibrotic gene expression, whereas Smad7 knockdown promoted matrix synthesis. In Smad7 KO fibroblasts, overactive fibrogenic activity was associated with enhanced Smad2/3, Erk and Akt signaling, but comparable TβRI/TβRII phosphorylation, suggesting that Smad7 acts downstream of the TGFβ receptors. To dissect the mechanisms for Smad7 actions, we compared the transcriptome of Smad7 KO and WT fibroblasts, in presence/absence of TGFβ. Surprisingly, Smad7 loss had more prominent effects on receptor tyrosine kinase (RTK) cascades than on TGFβ-inducible genes. An RTK protein array identified Erbbs as targets of Smad7 in fibroblasts. Western blot showed that Smad7 restrains Erbb1 and Erbb2 signaling through effects independent of TGFβ. In conclusion, Smad7 induction in infarct myofibroblasts restrains fibrosis, by inhibiting Smad2/3, Erk and Akt signaling via actions downstream of TβRs, and through TGFβ-independent interactions with Erbb1/2. Protective effects of Smad7 in cardiac remodeling may have important therapeutic implications for heart failure patients.
Abstract 16794: Characteristics, Trends, Outcomes, and Costs of Stimulant-Related Acute Heart Failure Hospitalizations in the United States
Authors: Shetty Suchith , Malik Aaqib h , Ali Abbas , Yang Ying Chi , BRIASOULIS Alexandros , Alvarez Paulino
Published: November 2020

Introduction:
Heart failure hospitalizations remains significant burden on the health care system. Simulants including cocaine and methamphetamine are amongst the most used illegal substances in the United States. The information regarding stimulant related heart failure hospitalizations is scarce.

Hypothesis:
We sought to evaluate the characteristics and trends of stimulants-related heart failure hospitalizations in the United States and their associated outcomes and resource utilization.

Methods:
Using the National Inpatient Sample (NIS), we identified patients with a primary diagnosis of heart failure hospitalization. These hospitalizations were further divided into those with and without a concomitant diagnosis of stimulant (cocaine or amphetamine) dependence or abuse. Survey specific techniques were employed to compare trends in baseline characteristics, complications, procedures, outcomes and resource utilization between the two cohorts.

Results:
We identified 9,932,753 hospitalizations (weighted) with a primary diagnosis of heart failure, of those 138,438 (1.39%) had a diagnosis of active stimulant use. The proportion of stimulant related ACHF hospitalization is on the rise (1.1% to 1.9%) as the mean age of these stimulant related ACHF hospitalizations (from 49.9 to 52 years). Stimulant related ACHF hospitalization mostly affects African Americans and the proportion of ACHF is highest amongst the age group of 30-39 years. It is associated with increased incidence of in-hospital complications but lower mortality and length of stay. These patients have more than 7-fold higher discharge against medical advice.

Conclusions:
Stimulant related heart failure hospitalizations have been increasing. Evaluation of in-hospital outcomes is limited by a high proportion of patients leaving against medical advice.
Abstract 16796: Machine Learning-Based Hepatic Fat Assessment in Low-Dose Coronary Artery Calcium Scans is Correlated With Human Reader Assessment
Authors: Modanwal Gourav , Walker Jonathan R , Al-Kindi Sadeer , Rajagopalan Sanjay , Madabhushi Anant
Published: November 2020

Introduction:
Hepatic attenuation on computed tomography (CT) is a surrogate marker for cardiometabolic risk, including Type 2 diabetes and its progression. Coronary artery calcium (CAC) screening for assessment of cardiovascular risk often includes portions of the liver and provides an opportunity for concomitant assessment of liver fat. However, the use of lower radiation dose CT and the need for reliable regions of interest (ROI) tracing creates challenges for routine clinical utilization. We present machine learning-based hepatic fat assessment (a) segmentation of liver and spleen and (b) CT attenuation measurement on low dose CT scans performed for CAC screening.

Methods:
Our approach (Figure 1a) comprises two steps. First, a deep learning-based model is utilized to segment the liver and spleen. Second, CT attenuation is measured on imaged organ volume. The segmentation model (U-Net with an EfficientNetB3 backbone) is trained with 5-fold cross-validation on 35 patients enrolled in the CLARIFY registry (clinicaltrials.gov NCT04075162) and validated on an independent set of 21 patients. The ground truth for segmentation is generated using Slicer 3D. Further, mean liver and mean liver-to-spleen CT attenuation is automatically measured on these scans and compared with manual ROI based assessment.

Results:
The segmentation model achieved a dice coefficient of 0.91 on the validation (Figure 1b). The automated volumetric assessment of liver and liver-to-spleen attenuation estimation showed a strong correlation with manual ROI assessment (Pearson correlation coefficient R=0.89 and R=0.88, respectively; Figure 1c).

Conclusions:
The presented machine-learning-based methods enable accurate estimation of liver and liver-to-spleen attenuation ratio on low-dose CAC CT scans. The approach needs to be further validated on larger, multi-institutional datasets to analyze its generalizability for hepatic fat assessment.