bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15034: Exposure to Secondhand Smoke is Associated With Increased Left Ventricular Mass
Authors: Skipina Travis M , Upadhya Bharathi , Soliman Elsayed Z
Published: November 2020

Background:
Exposure to secondhand smoke (SHS), or passive smoking, has been associated with chronic hypertension. However, little is known about the relationship between SHS and left ventricular (LV) hypertrophy, the most common complication of hypertension and a manifestation of cardiac end-organ damage.

Hypothesis:
SHS exposure is independently associated with LV mass.

Methods:
This analysis included 4,982 non-smoker participants (age 60.8±13.6 years, 57.8% women, 77.7% whites) from the Third National Health and Nutrition Examination (NHANES-III). Non-smoking was defined by self-report and serum cotinine ≤ 10 ng/dL, a biomarker for tobacco exposure. SHS was defined as serum cotinine level >1 ng/dL. LV mass was estimated using an electrocardiographic model developed and applied in NHANES-III then validated in the Cardiovascular Health Study. Multivariable linear regression was used to examine the cross-sectional association between SHS exposure (vs. no exposure) with estimated LV mass. In similar models, we also examined the associations of LV mass across quartiles of serum cotinine (reference group, 1
st
quartile) and in subgroups stratified by race, sex, and hypertension status.

Results:
About 9.8% (n=489) of the participants were exposed to SHS. Exposure to SHS was associated with an estimated 2.9 gram increase in LV mass, with a dose-response relationship between higher serum cotinine and LV mass (
Table
). These results were consistent in men and women (interaction p-value= 0.31), whites and non-whites (interaction p-value= 0.21), and those with and without hypertension (interaction p-value= 0.88)

Conclusion:
In a racially diverse sample of non-smokers, SHS is associated with increased LV mass with a dose-response relationship between level of exposure and LV mass. These findings underscore the harmful effect of passive smoking on the cardiovascular system and highlight the need for more restrictions on smoking in public areas.
Abstract 15035: Managing Covid-19 Amongst Pediatric Heart Transplant Recipients in Sao Paulo, Brazil
Authors: Azeka Estela , Arshad Adam , Jatene Marcelo B
Published: November 2020

Introduction:
Heart transplant recipients are considered high risk for poor outcomes following Covid-19 infection. However, there is minimal literature on the effects of Covid-19 on this cohort. We provide our centres experience, as a developing nation with limited resources, in the prevention and management of Covid-19 amongst pediatric heart transplant recipients.

Methods:
141 pediatric heart transplant recipients are currently followed-up at our centre - Heart Institute (InCor), Sao Paulo Medical School. We monitored this cohort using telephone contact, by which we postponed appointments and gave recommendations to stay home and maintain hygiene. Since March 2020, for any potential organ donations, a screening was conducted of the donor by taking a history, a RT-PCR-Covid 19 swab and performing a chest CT scan.

Results:
Five pediatric heart transplant recipients were suspected to have Covid-19 disease and two were tested positive for Covid-19. The first patient was a 14-year-old girl who underwent heart re-transplantation for coronary artery vasculopathy on March 5th, 2020. She developed significant haemodynamic compromise on post-operative day 45 and was transferred to ICU. Her chest CT showed extensive lung opacities (Figure 1). While attempting to wean her from mechanical ventilation, she had a sudden death. The second patient was a 6-year-old male. He presented to the hospital with vomiting, pyrexia, abdominal pain and nasal congestion. His chest CT scan demonstrated small nodule opacification of the lungs. He was appropriately commenced on fluids, antibiotics and antiviral medications. With improvements in his clinical state, he was discharged after 8-days.

Conclusions:
We provided telehealth to reduce the spread of Covid-19 amongst our cohort. However, we still had two Covid-19 positive cases at our centre. Our observations suggest that pediatric heart transplant recipients are at risk of deleterious outcomes from COVID-19 infection.
Abstract 15052: Association of Thiazide Diuretics Usage and Clinical Outcomes in Chronic Kidney Disease: Analysis of the Nationwide Cohort Study
Authors: Lin Hugo Y
Published: November 2020

Introduction:
Hypertension (HTN) is not uncommon in patients with chronic kidney disease (CKD). Thiazide diuretics (THZ) are widely used for the management of HTN. The clinical outcomes of THZ usage in patients with CKD remain uncertain.

Hypothesis:
The aim of this study is to examine the clinical effects of THZ usage in patients with CKD by utilizing a nationwide cohort.

Methods:
The THZ cohort included 8501 patients; each patient was age- and sex-matched with one THZ nonuser in the CKD population. The Cox proportional hazard regression analysis was conducted to estimate the effects of THZ on the mortality, incidence of end-stage renal disease (ESRD), congestive heart failure (CHF), acute myocardial infarction (AMI), peripheral arterial occlusive disease (PAOD) and stroke.

Results:
The mortality rate was significantly lower in THZ users than in THZ nonusers (hazard ratio [HR] = 0.65; 95% confidence interval [CI] = 0.60-0.71,
p
<0.001). The HR for the incidences of ESRD, AMI, PAOD and stroke were significantly (
p
<0.05) lower in THZ users (HR=0.71, CI= 0.66-0.77; HR=0.82, CI=0.76-0.89; HR=0.68, CI=0.63-0.74; HR=0.91, CI=0.84-0.98) than in THZ nonusers. In THZ subgroup analysis, clothalidone users had significantly lower incidences of mortality, ESRD, and PAOD (HR=0.62, CI= 0.40-0.97,
p
=0.037; HR=0.54, CI=0.36-0.82,
p
=0.004; HR=0.60, CI=0.39-0.94,
p
=0.026) than nonusers. Indapamide users had significant lower incidences of mortality, ESRD, AMI and PAOD (HR=0.64, CI= 0.57-0.71,
p
<0.001; HR=0.72, CI=0.65-0.79,
p
<0.001; HR=0.89, CI=0.81-0.98,
p
=0.018; HR=0.69, CI=0.62-0.78,
p
<0.001) than nonusers. However, Metolazone users had significantly higher incidences of ESRD, CHF, and AMI (HR=1.28, CI= 1.06-1.54,
p
=0.009; HR=1.60, CI=1.33-1.92,
p
<0.001; HR=1.41, CI=1.08-1.59,
p
=0.007) than nonusers.

Conclusions:
In patients with CKD who receive therapy with THZ, both clothalidone and Indapamide users exhibit significantly beneficial effects of mortality, ESRD, and PAOD. Indapamide users revealed significantly advantageous results of AMI. However, Metolazone users had significantly higher incidences of ESRD, CHF, and AMI. A further randomized control trial to clarify the effect of THZ usage in patients with CKD is a necessity.
Abstract 15055: Quantitative Echocardiography of the Left Atrium: Traditional Measurement by Manual Planimetry Can be Replaced by Automated Four-dimensional Imaging That is More Efficient and Provides Additional Information
Authors: Nguyen Thuy , Wong Jonathan , Abouzeid Christiane , Bibby Dwight , Fang Qizhi , Lu Dai-Yin , Schiller Nelson B
Published: November 2020

Background:
Manual volume measurement of the left atrium (LA) using two-dimensional (2D) imaging is time consuming and mainly produces volumetric information.

Hypothesis:
LA chamber quantification by semi-automated four-dimensional (4D) imaging may be more efficient and produces both volume and comprehensive functional analysis.

Methods:
Fifty subjects from the Healthy eHeart cohort of normal echocardiograms studied at the Research Cardiac Physiology Laboratory were selected by representative LA volumes. Studies were performed on a GE Vivid E95. Plainimetry was done on LA 2D images from apical 2 and 4 chamber views. Biplane LA maximal volume index (LAVImax) and minimal volume index (LAVImin) were calculated by method of discs. LA 4D images were obtained from an apical 4 chamber view. LA volume was calculated using a commercially available 4D Auto LAQ package. All 2D and 4D measurements were repeated at random by a sonographer. Analysis times for each LA volume quantitation were recorded. Intra-observer reproducibility was analyzed by coefficient of variation (CV).

Results:
Mean age of subjects was 51 ± 17 years (60% male). On 2D analysis, mean LAVImax was 26.7 ± 9.5 ml/m2 and mean LAVImin was 10.9 ± 4.4 ml/m2. Intra-observer reproducibility showed a CV of 9.1% for LAVImax and 8% for LAVImin. On 4D analysis, mean LAVImax was 27.2 ± 8.9 ml/m2 and mean LAVImin was 11.8 ± 3.9 ml/m2. Intra-observer reproducibility showed a CV of 4.0% for LAVImax and 5.0% for LAVImin. Time for LA volume quantification was 74 ± 15 seconds for 4D vs. 195 ± 30 seconds for 2D, p < 0.001. The 4D analysis offered a LA volume curve, LA global longitudinal strain, and a real time 4D LA image that 2D did not.

Conclusion:
Acquisition and analysis of LA volume by 4D echocardiogram using a 4D Auto LAQ package requires less time than 2D analysis while producing a more comprehensive and reproducible result. It is worth considering advancing 4D LA quantification to a first-line method in clinically quantitating LA function.
Abstract 15057: Electromechanical Discoordination is Present in Patients With Duchenne Muscular Dystrophy Independent of Tissue Fibrosis
Authors: Hoffner Heinike Alex , Schafer Michal , Frank Benjamin , IVY Dunbar D , Barker Alex , Browne Lorna , Di Maria Michael , Fonseca Brian , Miyamoto Shelley D , Auerbach Scott R
Published: November 2020

Introduction:
Progressive ventricular dysfunction is a cardinal symptom in Duchenne Muscular Dystrophy (DMD). Some of the earliest signs of cardiomyopathy in DMD are myocardial fibrotic deposition and LV strain defects. Electromechanical discoordination, as measured by Systolic Stretch Fraction (SSF) and Diastolic Relaxation Fraction (DRF), has been shown to be a sensitive marker of ventricular dysfunction. The presence of this discoordination in relation to fibrotic deposition in DMD has yet to be elucidated.

Hypothesis:
Patients with DMD will have abnormal SSF and DRF on cardiac MRI (CMR) tissue tracking analysis and associated with fibrotic deposition.

Methods:
Patients with DMD (n=31)(mean age: 14 ± 4 yrs) and controls (n=20) (mean age: 15 ± 3 yrs) underwent CMR for volumetric and functional analysis as well as Gadolinium (Gd) enhancement to evaluate the presence of fibrosis. Circumferential strain and strain rate indices from each segment were used to calculate electromechanical discoordination. Strain rate data was used to calculate SSF and DRF.

Results:
Patients with DMD showed increased median LV SSF compared to controls [0.027 (IQR: 0.015-0.041) vs 0.007 (IQR:0.005-0.013), P = 0.002] as well as increased median LV DRF [0.371 (IQR: 0.310-0.473) vs 0.300 (IQR: 0.264-0.325), P < 0.001] (Figure). When comparing Gd(+) (n=14) vs Gd(-) (n=17) DMD patients, there was no difference between groups in either SSF [0.027 (IQR: 0.016-0.042) vs 0.026 (IQR: 0.008-0.040), P= 0.929] or DRF [0.371 (IQR: 0.309-0.537) vs 0.379 (IQR: 0.322-0.464), P= 0.931]. The SSF was associated with ESVi (R=0.71, P<0.001), EDVi (R=0.65, P< 0.001) and inversely associated with EF (R=-0.63, P<0.001).

Conclusion:
Patients with DMD showed increased levels of LV electromechanical discoordination independent of qualitative presence of fibrosis noted by Gd enhancement. This allows speculation that changes in electromechanical discoordination may precede visible fibrotic change in DMD.
Abstract 15059: Prevalence of Recovery of Conduction in the Left Atrial Appendage Following Electrical Isolation of the Appendage in Patients With Atrial Fibrillation
Authors: Mohanty Sanghamitra , TRIVEDI CHINTAN G , Della Rocca Domenico G , Gianni Carola , Baqai Faiz M , MacDonald Bryan , Mayedo Angel , Bassiouny Mohamed , Gallinghouse G , Burkhardt John , Horton Rodney , Di Biase Luigi , Al-ahmad Amin , Natale Andrea
Published: November 2020

Background:
Electrical isolation of the left atrial appendage (LAAEI) is considered in patients presenting with recurrence following effective PV isolation.

Objective:
We evaluated the prevalence of LAA reconnection following LAAEI in patients undergoing repeat procedure for AF recurrence.

Methods:
Consecutive AF patients undergoing repeat ablation for arrhythmia recurrence following LAAEI were included in this analysis. Transesophageal echocardiogram (TEE) was performed in all at baseline to evaluate LAA function. Isoproterenol infusion up to 30 μg/min for 10 to 15 min was administered to detect LAA triggers. Re-isolation of the LAA was performed if triggers were detected. Off-drug success rate was assessed in all.

Results:
A total of 594 post-LAAEI patients with recurrent AF were included in the analysis. At the redo, PVs were found to be electrically silent in all. LAA reconnection was detected in 214 (36%) patients. Baseline TEE revealed normal LAA contractility and flow-velocity in all. Re-isolation of the LAA was performed in these 214 patients. In patients with no LAA reconnection (n=380), non-PV triggers from other sites were targeted for ablation. There was no difference in the clinical characteristics of patients with vs. without LAA reconnection (Table). At 2 years after the repeat procedure, 201 (94%) patients with and 351 (92.3%) without LAA reconnection were arrhythmia-free off-drugs (p=0.47).

Conclusion:
In this series, LAA reconnection rate was 36% after single LAAEI procedure and re-isolation of the appendage led to high success rate. Additionally, normal LAA functions detected by TEE correctly predicted recovery of conduction in the LAA.
Abstract 15065: Impact of Ablation Strategy on Left Ventricular Function Following Catheter Ablation in Patients With Long-standing Persistent Atrial Fibrillation and Heart Failure: Results From a Single-center Study
Authors: Mohanty Sanghamitra , TRIVEDI CHINTAN G , Baqai Faiz , Della Rocca Domenico G , Gianni Carola , MacDonald Bryan , Mayedo Angel , Burkhardt John , Gallinghouse G , Al-ahmad Amin , Horton Rodney , Bassiouny Mohamed , Di Biase Luigi , Natale Andrea
Published: November 2020

Background:
Ablation strategy for long-standing persistent atrial fibrillation (LSPAF) is highly variable with diverse outcomes.

Objective:
We evaluated the change in left ventricular ejection fraction (LVEF) with different ablation approaches in LSPAF patients with heart failure (HF).

Methods:
Consecutive LSPAF patients with HF (LVEF <40%) undergoing their first catheter ablation at our center were included in the analysis. Based on the ablation strategy determined by the operators, patients were classified into two groups;
group 1:
received standard ablation (PV isolation+ isolation of left atrial posterior wall and superior vena cava) and
group 2:
standard ablation plus isolation of coronary sinus (CS) and left atrial appendage (LAA). High-dose isoproterenol challenge (20-30 μg for 10-15 min) was utilized to reveal LAA and CS triggers; electrical isolation was the procedural endpoint for LAA and CS ablation. If PVs were electrically silent due to presence of severe scar, LAA and CS were empirically isolated even in the absence of detectable triggers. LVEF was measured by transesophageal echocardiogram (TEE) performed at baseline and 6 months post-ablation. Patients were monitored for arrhythmia-recurrence off-antiarrhythmic drugs (AAD) as per our standard protocol.

Results:
Group 1 included 52 patients and group 2 had 106. Baseline characteristics were comparable across groups (age: 66.2 ± 7.3 and 64.4 ± 9.4; male: 41 (78.8%) and 87 (82.1%); BMI: 32.3 ± 6.8 and 30.4 ± 6.4 in group 1 and 2). Mean baseline LVEF (%) was 36.2±5.5 and 35.1±8.3 in group 1 and 2 respectively (p=NS). At the 6-month TEE, mean LVEF was significantly higher than the baseline value in group 2 (47.7±11 vs 35.1±8.3, p<0.001), whereas in group 1, although there was a positive trend, the change was statistically non-significant (39.4±10 vs. 36.2±5.5, p=0.36). A total of 7 (13.5%) patients from group 1 and 89 (84%) from group 2 were arrhythmia-free off-AAD at 1.5 year of follow-up (p<0.001).

Conclusion:
In our study population, ablation strategy including LAA and CS isolation along with the standard ablation resulted in significant improvement in the LVEF as well as higher rate of arrhythmia-free survival.
Abstract 15066: Cost Comparison of Handmade versus Commercially Available Grafts Used for Pediatric Right Ventricular Outflow Tract Reconstruction
Authors: Mistry Maanasi S , WEST Shawn C , VIEGAS MELITA , castro medina mario , Morell Victor O
Published: November 2020

Introduction:
Handmade polytetrafluoroethylene (PTFE) conduits have similar durability and efficacy compared to commercially available conduits and homografts used for pulmonary valve replacement (PVR) in pediatric right ventricular outflow tract (RVOT) reconstruction. We evaluated the costs related to use of the PTFE conduits compared to commercial grafts.

Hypothesis:
When compared to commercial grafts in first-time RVOT reconstruction, PTFE conduits have reduced surgical day costs with similar overall hospital costs per day of conduit life.

Methods:
Data was collected via retrospective chart review of patients < 2 years of age who underwent first-time PVR from 1/2010 - 3/2019. Initial procedure, all day-of-surgery, and subsequent reintervention costs and charges were examined. Patients were followed until conduit explant, patient death, or 3/2020 (whichever came first) and were adjusted to 2020 USD.

Results:
Of 52 instances of PVR in RVOT reconstruction, 36 (69%) of grafts were PTFE, and 16 (31%) were commercial. There were no statistically significant differences in gestational age; birth weight; weight, height, or age at intervention; hospital or intensive care unit length of stay; conduit life; or bypass, cross-clamp, or intubation duration between the groups. Compared to commercial grafts, PTFE conduits were associated with lower day-of-surgery hospital charge, day-of-surgery estimated cost, and graft/conduit charge. There was a trend toward lower aggregate cost over conduit life (Table). Aggregate cost per day of conduit life was similar between groups (
p
= 0.26).

Conclusions:
In first-time PVR, PTFE conduits have lower initial and reintervention costs compared to commercially available conduits and homografts. In centers with expertise in handmade conduits, these may provide a less expensive alternative to commercial grafts in pediatric patients requiring RVOT reconstruction.
Abstract 15082: Repolarization Vulnerability is Rarely Observed in COVID-19 Patients With Low Comorbidity Treated With a Combination of Hydroxychloroquine Azithromycin
Authors: Goldgrab David E , Kalaveshi Sokol , Yang Ruifang , Gomez Mauricio , Craig Jearim , Mester Stephen , Perzanowski Christian
Published: November 2020

Background:
Global pandemic of COVID-19 has attracted a number of proposed treatment therapies. Hydroxychloroquine/Azithromycin (HA) combination has been reported to potentially affect repolarization by prolonging the QTc and causing torsades de pointes (TdP).

Methods:
We prospectively followed hospitalized patients with PCR confirmed COVID-19. Hydroxychloroquine was administered 400mg twice daily on day 1 and daily for the last 4 days plus daily Azithromycin 250mg. QTc interval was measured via 12 lead ECG prior to initiation of therapy, 3 hours post second dose of hydroxychloroquine, and subsequent daily QTc evaluation via telemetry. Potassium and magnesium were checked daily and replaced accordingly. QTc prolonging medications were discontinued when possible.

Results:
Sixteen patients were followed for 5 days, 56% were male with average age of 67. Comorbidities were 31% coronary artery disease, 31% diabetes mellitus, 13% congestive heart failure, 69% hypertension, 19% chronic obstructive pulmonary disease, 25% atrial fibrillation, and average BMI of 29. Average Tisdale score was 11/21. Mean QTc prior to HA therapy was 442 ms, 3 hours post second dose 429 ms and on day 5 was 441 ms with a change of (-)3ms compared to prior starting therapy as seen in figures below. Fifteen patients recovered and 1 patient expired. Twenty five percent of patients required ET intubation and mechanical ventilation. Zero patients required stopping of HA therapy. Only 1 patient required 2 extra days of QTc monitoring due to 5th day QTc being 504ms.

Conclusion
In acutely infected COVID-19 patients with limited comorbidities, repolarization/risk for TdP appears to be low in the presence of HA. With close monitoring and the right patient population, this combination therapy for short term treatment appears to be safe in regards to QTc and the risk for TdP. Although larger published studies have shown repolarization risk, we did not find that to be the case in our relatively healthy population.
Abstract 15087: Identifying Clinical Predictors of Mortality After PCI and the Impact of Complete Revascularization in Patients With Multi-vessel Coronary Artery Disease
Authors: Safiullah Zaid N , Zhu Jianhui , Toma Catalin , Thoma Floyd W , Smith Anson J , MARROQUIN Oscar C , Fowler Jeffrey A , Schindler John T , Mulukutla Suresh R
Published: November 2020

Coronary revascularization for multi-vessel coronary artery disease (mvCAD) can be established through PCI or CABG. The benefit of surgical intervention over PCI has been attributed, in part, to more complete revascularization. However, among patients treated with PCI in the present era of drug-eluting stents, it is important to understand whether the completeness of revascularization is associated with mortality. Further, it is important to investigate this relationship in specific patient populations to determine which patients, if any, derive a survival benefit from complete revascularization. Moreover, it is critical to identify which factors are associated with higher mortality in this population to pinpoint potential areas of intervention to mitigate risk. In this propensity-score adjusted analysis, outcomes among 1,580 mvCAD patients who underwent PCI were analyzed and stratified by complete versus incomplete revascularization. The primary outcome was all-cause mortality. Complete revascularization was achieved in 28.4% of the cohort. Complete revascularization was not independently associated with survival compared with incomplete revascularization in the overall cohort (p=0.16). The predictors of increased all-cause mortality included advanced age, chronic lung disease, cardiogenic shock, diabetes, renal insufficiency, reduced left ventricular function, and left main stenosis. Complete revascularization was associated with reduced all-cause mortality in specific patient subsets including those with congestive heart failure and chronic lung disease. Our analysis elucidated numerous clinical predictors of all-cause mortality for mvCAD patients undergoing PCI. Complete revascularization was not among the independent predictors of mortality in the overall population and was associated with reduced mortality in patients with chronic lung disease, history of congestive heart failure and those who did not have previous PCI. While this study was not designed to test whether complete revascularization was superior to incomplete revascularization, the results suggest that when PCI is pursued among patients with mvCAD, achieving complete revascularization does not contribute to increased mortality.
Abstract 15090: Direct Oral Anticoagulation vs Vitamin K Antagonist in Atrial Fibrillation With Liver Disease: A Systematic Review and Meta-analysis
Authors: El Iskandarani Mahmoud , Shatla Islam , Khalid Muhammad , El Kurdi Bara , Paul Timir , Refaat Marwan M
Published: November 2020

Background:
Current guidelines recommend against the use of direct oral anticoagulation (DOAC) therapy in patients with atrial fibrillation (AF) in the setting of significant liver disease (LD) due to lack of evidence in safety and efficacy studies. However, recently studies have investigated the role of DOAC in comparison to Vitamin K antagonist (VKA) in this category of patients. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this approach.

Hypothesis:
DOAC is safe and effective compared to VKA in AF with LD patients.

Method:
Unrestricted search of the PubMed, EMBASE, and Cochrane databases performed from inception until June 1, 2020 for studies comparing DOAC with VKA including more than 100 AF patients with LD. Relevant data were extracted and analyzed using Revman 5.3 software. Hazard ratio (HR) and 95% Confidence interval (CI) were calculated using the random-effects model.

Result:
A total of 5 studies (3 retrospective and 2 post hoc analysis) were included examining 39,064 patients with AF and LD (25,398 DOAC vs 13,669 VKA). DOAC is associated with lower risk of major bleeding compared to VKA with a HR of 0.68 (95% CI 0.47-0.98; I
2
=53%), all-cause mortality (HR 0.74;95% CI 0.59-0.94; I
2
=61%), and intracranial bleeding (HR 0.48; 95% CI 0.40-0.58; I
2
=0). There was no significant difference in ischemic stroke risk (HR 0.73; 95% CI 0.47-1.14; I
2
=72%) and gastrointestinal bleeding risk (0.96; 95% CI 0.61-1.51; I
2
=41%) between DOAC and VKA.

Conclusion:
DOAC is non-inferior to VKA regarding ischemic stroke prevention in AF patients with LD. Moreover, DOAC is associated with a lower risk of major bleeding, intracranial bleeding and all-cause mortality. Further randomized trials are needed to validate our findings.
Abstract 15091: Significant Reductions in Both Adjudicated and Investigator-Reported Ischemic Events in REDUCE-IT
Authors: Bhatt Deepak L , Giugliano Robert , Steg Philippe G , Miller Michael , Brinton Eliot A , Jacobson Terry A , Ketchum Steven , Juliano Rebecca , Jiao Lisa , Doyle Ralph , Granowitz Craig , Tardif Jean-Claude , Ballantyne Christie M , Pinto Duane S , Budoff Matthew J , Gibson C M
Published: November 2020

Introduction:
REDUCE-IT was an event-driven trial that randomized 8,179 statin-treated patients with controlled LDL-C and moderately elevated triglycerides to icosapent ethyl (IPE) 4g daily or placebo, with a median of 4.9 years of follow-up. There was a significant reduction in the prespecified adjudicated rates of the primary endpoint (cardiovascular [CV] death, non-fatal myocardial infarction [MI], non-fatal stroke, coronary revascularization, and unstable angina requiring hospitalization) and of the key secondary endpoint (CV death, MI, stroke), as well as in all the primary endpoint components. We sought to determine the effect of IPE on investigator-reported events.

Methods:
The Clinical Endpoint Committee (CEC) blindly adjudicated investigator-reported events according to a prespecified charter. Medical records and reports were also reviewed to assess for clinical events not reported by investigators. An endpoint management team compiled and electronically provided event packets to the CEC via an adjudication database. The CEC Chair provided final adjudication if the two primary adjudicators could not reach consensus.

Results:
IPE significantly reduced the rate of the primary endpoint (hazard ratio 0.74, p=0.0000000002) and the key secondary endpoint (hazard ratio 0.75, p=0.000007) as reported by the site investigators, with consistent benefits in each component of the primary endpoint (Table). There was a high degree of concordance between investigator-reported and adjudicated endpoints.

Conclusions:
Icosapent ethyl significantly reduced multiple types of ischemic events, both by independent, blinded adjudication as well as by investigator-reported assessment. These results underscore the robustness of the benefits of icosapent ethyl seen in REDUCE-IT.
Abstract 15096: Electrocardiographic QRS Amplitude Predicts Mortality in Hospitalized Patients With CoViD-19
Authors: Lampert Joshua , Halperin Jonathan , Giustino Gennaro , Oates Connor , Nelson Kyle , Feinman Jason , Pulaski Matthew , Musikantow Daniel , Turagam Mohit , Miller Michael , langan marie-noelle , Koruth jacob s , Dukkipati Srinivas , Miller Marc , Whang William , Goldman Martin , Fuster Valentin , Reddy Vivek Y
Published: November 2020

Introduction:
In a variety of cardiovascular diseases, low QRS voltage amplitude on the 12-lead ECG is associated with poor prognosis. We studied the relative frequency and importance of this phenomenon in hospitalized patients with SARS-coronavirus 2019 (CoViD-19) - a condition associated with myocardial injury in ~1/3 of patients.

Methods:
We performed a retrospective analysis of 800 consecutive patients with laboratory-confirmed CoViD-19 hospitalized from Mar 7 and Apr 12, 2020. Patients without a final disposition or telemetry data were excluded, resulting in 140 patients. On 12-lead ECG, low amplitude was defined as QRS amplitude <5mm in II/III/aVF, <10 mm in V1-V6, or a ≥50% decrease in amplitude on follow-up ECG during hospitalization, relative to the baseline/admission ECG. The association of 14 clinical variables to mortality was tested in multivariable logistic regression models.

Results:
Among 140 patients, 33 (23.6%) met criteria for low QRS amplitude. Compared to patients
without
low amplitude, these patients had a higher risk of in-hospital mortality (72.7% vs 26.2%; p<0.0001) and mechanical ventilation (63.3% vs 32.4%; p=0.002). In multivariable models, there were only 3 independent predictors of in-hospital death: age (OR=1.1, 95% CI 1.0-1.1, p<0.001), BMI (OR=1.1, 95% CI 1.1-1.2, p0.001), and the strongest predictor, low amplitude (OR=7.2; 95% CI 2.3-23.0). Low amplitudes in either the limb or precordial leads both predicted death (Table).

Conclusions:
A reduction in electrocardiographic QRS amplitude in patients with CoViD-19 is the strongest clinical predictor of death, and may be useful for risk stratification during hospitalization. Further study is needed to elucidate the mechanisms underlying changes in QRS amplitude, and their relationship to disease severity.
Abstract 15391: The Natural History of Asymptomatic and Mildly Symptomatic Obstructive Hypertrophic Cardiomyopathy: Insights From the Share Registry
Authors: Ahluwalia Monica , Han Larry , olivotto iacopo , Ashley Euan A , Michels Michelle , Ingles Jodie , Semsarian Christopher , Jacoby Daniel L , Colan Steven , Pereira Alexandre D , Joseph Rossano W , Wittekind Sam , Ware James S , Saberi Sara , Helms Adam S , Day Sharlene , Ho Carolyn , Lakdawala Neal K
Published: November 2020

Background:
Contemporary studies are needed to determine the natural history of asymptomatic and mildly symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM).

Methods:
Patients with HCM, peak left ventricular outflow tract (LVOT) gradient ≥30 mm Hg (at rest, post-Valsalva, or exercise) and baseline NYHA I-II symptoms were identified using the multicenter Sarcomeric Human Cardiomyopathy Registry (SHaRe). Patients with prior atrial fibrillation (AF) or septal reduction therapies (SRT) were excluded. Incident outcomes, including the composite of NYHA III-IV symptoms, AF or SRT, were related to LVOT using Kaplan-Meier analysis (LVOT tertiles) and Cox proportion hazard models, controlling for age, sex, race, proband status, sarcomere status, hypertension and left atrial diameter.

Results:
At baseline, the 1048 patients who met inclusion criteria were 52.0 ± 16.1 yrs, 48.9% female, 34.9% sarcomere mutation +, with mean LVOT gradient 72 ± 39mm Hg. Over 8.6 years follow up (IQR 2.3, 13.6), progression to the composite endpoint ocurred in 530 (50.6%) and 92 (8.8%) died. Patients in the highest tertile of LVOT gradient (>84 mm Hg) were at increased risk of the composite endpoint (Figure). Every 10 mm Hg increase in LVOT gradient was associated with increased risk of incident NYHA III-IV HF (HR 1.04, 95% CI 1.00, 1.08, p=0.04), SRT (HR 1.07, 95% CI 1.04, 1.09, p<0.001) and the composite endpoint (HR 1.03, 95% CI 1.01, 1.06, p=0.003), but not incident AF (HR 1.02, p=0.39) or death (HR 0.99, p=0.3). Older age (HR 1.01, 95% CI 1.00-1.03, p=0.03), black race (HR 1.73, 95% CI 1.11-2.69, p=0.02) and sarcomere mutations (HR 1.27, 95% CI 1.02-1.59, p=0.03) were also associated with increased risk of the composite endpoint.

Conclusions:
In oHCM patients with NYHA I-II symptoms, the LVOT gradient appears to predict worsening symptoms and need for SRT, but not AF or overall survival. These findings have implications for refining management strategies for oHCM.
Abstract 15402: A Multi-ethnic Genome Wide Association Study of Aortic Stenosis in the Million Veteran Program Identifies Several Novel Loci
Authors: Small Aeron M , Peloso Gina , Aragam Jayashri , LINEFSKY JASON , Galloway Ashley , Cho Kelly , WILSON PETER , Thanassoulis George , O'Donnell Christopher J
Published: November 2020

Introduction:
Valvular aortic stenosis (AS) is common with high morbidity and mortality in the absence of surgical intervention, but no current medical therapies are known to prevent or slow disease progression. Previous genetic studies have identified several genetic loci associated with prevalent AS, including
LPA
and
PALMD
, although most evidence is limited to populations of European ancestry.

Methods:
We performed a trans-ethnic genome-wide association study (GWAS) of prevalent AS in the Veterans Administration Million Veteran Program (MVP). Cases were identified by a combination of diagnostic billing and surgical codes and validated by association to the known LPA variant (rs10455872). GWAS was run separately for White, Black, and Hispanic individuals, controlling for age, sex, and six principal components, and combined using fixed effects meta-analysis. Results were limited to variants with a minor allele frequency greater than 1% in the trans-ancestry analysis. Lead independent genome wide significant loci were annotated by nearest gene.

Results:
300,182 White, 80,744 Black, and 32,069 Hispanic participants were available for analysis. Of these, there were 12,385 (4.1%) White, 1,444 (1.8%) Black, and 611 (1.9%) Hispanic AS cases. Trans-ethnic analyses identified 10 independent genome wide significant (GWS, p≤5x10
-8
) loci, replicating 6 known AS genetic loci (
ALPL, PALMD, TEX41, LPA, IL6, FADS1
), and identifying 4 novel genetic loci (
CEP85L, CELSR2, NCK1, SLMAP
), of which 2 were present at nominal significance in Hispanic (
CELS2R
) or Black (
SLMAP
) individuals. Ethnicity-specific analyses additionally identified 9 novel GWS loci in White individuals, and 3 novel GWS loci in Hispanic individuals. Newly identified loci supported known biological pathways in AS including lipid/metabolic, inflammatory, and calcification, but also implicated new pathways such as those pertaining to QT interval (
SLC35F1
) and the Brugada Syndrome (
SLMAP
).

Conclusions:
In this large trans-ethnic GWAS for AS we replicate previously identified genetic loci for AS, and identified several novel loci both in trans-ethnic and in ethnic-specific analyses. These loci implicate known and novel biological mechanisms for future prevention and treatment of AS.
Abstract 15413: Building New Arteriogenic Therapy for Ischemic Cardiomyopathyusing Notch-induced Mesenchymal Stem Cell Patch
Authors: Maeda Shusaku , Miyagawa Shigeru , Kawamura Takuji , Chida Dai , Shibuya Takashi , Ueno Takayoshi , Sawa Yoshiki
Published: November 2020

Introduction:
The induction of arteriogenesis is a promising approach for treatment of ischemic cardiomyopathy. Notch signaling has been reported to be a key regulator of arteriogenesis.

Hypothesis:
We hypothesized that Notch-induced human mesenchymal stem cell (SB623) sheet transplantation would induce arteriogenesis in ischemic lesion, leading to improvement of left ventricular function in ischemic cardiomyopathy model rats.

Methods:
Two weeks after the ischemic induction, SB623-patches were transplanted to myocardial infarction model rats (SB group, n=10) or shame operations were performed (Control group, n=10). We evaluated cardiac performance and histology six weeks after the treatment in vivo. In vitro, we performed RNA-sequencing of human umbilical vein endothelial cells (HUVECs) cocultured with SB623s.

Results:
Left ventricular ejection fraction was significantly improved 6 weeks after SB623-sheets transplantation (LVEF, 52±7% vs. 34±5%, p<0.001). Similarly, the attenuation of LV remodeling was observed at 6 weeks (LV diastolic dimension, 73±7 mm vs. 85±5 mm, p<0.001). Histological findings revealed that fibrosis was decreased in SB group (11±1% vs. 22±4%, p=0.02). Furthermore, vWF-positive capillary vessels (vessels, 516±110 /mm
2
vs. 248±26 /mm
2
, p<0.001) and αSMA- and vWF-positive arterioles with over 20μm diameter (arterioles, 25±8 /mm
2
vs. 6±3 /mm
2
, p=0.002) were significantly increased in SB group, suggesting the induction of angiogenesis and arteriogenesis. In vitro, whole transcriptome analysis showed that Notch signaling pathway was significantly upregulated (p<0.001) in HUVECs co-cultured with SB623s. Similarly, pathway analysis revealed upregulated “fluid shear stress and atherosclerosis” pathway (p<0.001) in vitro, suggesting an arteriogenic response of endothelial cell. In vivo study, upregulations of ephrin-B2 (p=0.03) and EphB4 (p=0.01) gene expressions in SB group were confirmed, indicating both arterial and venous remodeling induced by Notch signaling.

Conclusions:
SB623 patch transplantation induces arteriogenesis with functional recovery via Notch signaling in rat myocardial infarction model, proposing a new strategy for the treatment of ischemic cardiomyopathy.
Abstract 15414: Diagnostic Performance of Deep Learning on 12-lead Electrocardiography to Distinguish Takotsubo Syndrome and Acute Anterior Myocardial Infarction
Authors: Shimizu Masato , cho shummo , Misu Yoshiki , Ohmori Mari , Tateishi Ryo , Kaneda Toshio , Yamakami Yosuke , Shimada Hiroshi , Manno Tomoko , Isshiki Ami , Kimura Shigeki , Hiroyuki Fujii , Suzuki Makoto , Nishizaki Mitsuhiro , Sasano Tetsuo
Published: November 2020

Introduction:
Takotsubo syndrome (TTS) and acute anterior myocardial infarction (ant-AMI) show very similar 12-lead electrocardiography (ECG) featured at onset, and it is often difficult to distinguish them without cardiac catheterization. The difference of ECG between them was studied, but the diagnostic performance of machine learning (deep learning) for them had not been investigated.

Hypothesis:
Deep learning on 12-leads ECG has high diagnostic performance to diagnose TTS and ant-AMI at onset.

Methods:
Consecutive 50 patients of TTS were one-to-one matched to ant-AMI randomly by their age and gender, and total 100 patients were enrolled. No sinus rhythm patients were excluded. All ECGs were divided into each 12-lead, and 5 heart beats from one lead were extracted. For each lead, 250 ECG waves of TTS/AMI were sampled as 24bit bitmap image, and prediction model construction by convolutional neural network (CNN: transfer learning, using VGG16 architecture) underwent to distinguish the two diseases in each lead. Next, gradient weighted class activation color mapping (GradCam) was performed to detect the degree and position of convolutional importance in the leads.

Results:
Lead aVR (mean accuracy 0.748), I (0.733), and V1 (0.678) were the top 3 leads with high accuracy. In aVR lead, GradCam showed strong convolution of negative T wave in TTS, and sharp R wave in ant-AMI. In I lead, it spotlighted several parts of ECG wave in ant-AMI. However in TTS, whole shape of the wave, P wave onset, and negative T were invertedly convoluted in TTS.

Conclusions:
Deep learning was a powerful tool to distinguish TTS and ant-AMI at onset, and GradCam method gave us new insight of the difference on ECG between the two diseases.
Abstract 15417: Impact of Udenafil on Vascular Function in Fontan Circulation: Results From the FUEL Trial
Authors: Goldstein Bryan H , Goldberg David J , Paridon Stephen , Lam Chen Quin Eric , Ranganathan Gayatri , Jean-st-michel Emilie M , Rathod Rahul , Krishnan Usha S , Chamberlain Reid , Jackson Lanier , Ware Adam , Detterich Jon A , Ginde Salil , Sassalos Peter , Schamberger Marcus S , Petit Christopher , Shahanavaz Shabana , Garuba Olukayode D , woodford edward j , Weingarten Angela , Mietus-Snyder Michele , White David A , DiMaria Michael , Conner Colin , Christensen Jason , Khoury Michael , Yoon Ja Kyoung , Prospero Carol , zak victor , Urbina Elaine M ,   Pediatric Heart Network Investigators
Published: November 2020

Introduction:
In the Pediatric Heart Network double-blind Fontan Udenafil Exercise Longitudinal (FUEL) trial, treatment with udenafil (Mezzion Pharma Co Ltd) for 6 months was associated with modest improvements in exercise capacity and ventricular performance (NCT02741115). Measures of vascular function, which have been related to Fontan exercise capacity, were also obtained but have not been explored in detail.

Methods:
Endothelial function (Framingham reactive hyperemia index, FRHI; area under the curve to max occlusion, AUC
Max
) and arterial stiffness (augmentation index, AI) were assessed with peripheral arterial tonometry. The primary outcome was the effect of udenafil vs. placebo on vascular function. Secondary outcomes included baseline, and 26-week change from baseline, measures of vascular function in subgroups of the udenafil arm, stratified by exercise response. Exercise response was defined by longitudinal change in peak oxygen consumption and categorized by 1) any positive change vs. other and 2) tertile of change.

Results:
Paired measures of vascular function were analyzed in 164 (82%) and 167 (84%) udenafil and placebo participants, respectively. There were no baseline differences between groups, including the use of vasoactive medications. Overall, there were no differences in change in measures of vascular function between treatment groups. In subgroup analysis, exercise responders demonstrated better baseline endothelial function (FRHI: 0.39 ± 0.37 vs. 0.29 ± 0.31, p=0.056; AUC
Max
: 6.53 ± 2.91 vs. 5.63 ± 2.21, p=0.023) and suggestion of a 26-week reduction in arterial stiffness (AI: -1.42 ± 10.3 vs. 1.69 ± 11.7, p=0.075). Analysis by tertile of exercise response showed that AI was significantly improved in the top tertile of exercise responders (-3.27 ± 8.4 vs. 2.62 ± 12.4 vs. 0.35 ± 11.1, p=0.022) compared with the lower tertiles.

Conclusions:
In the FUEL trial, treatment with udenafil was not associated with significant changes in measures of vascular function. Udenafil-treated participants with evidence of exercise responsiveness to therapy manifest better baseline endothelial function and a significant improvement in arterial stiffness. Vascular function may play a role in PDE-5 responsiveness in Fontan circulation.
Abstract 15422: Distribution of 10- and 30-year Predicted Risks for Heart Failure in the United States: NHANES 2015 to 2018
Authors: Shah Nilay S , Ning Hongyan , Shah Sanjiv J , Yancy Clyde , Wilkins John T , Lloyd-jones Donald M , Khan Sadiya
Published: November 2020

Introduction:
Heart failure (HF) poses a significant health burden with prevalence projected to increase by 46% by 2030 in the United States. Targeted implementation and dissemination of clinical and public health preventive measures across the life course will be informed by describing population distributions of short- and long-term predicted HF risk.

Methods:
Among nonpregnant middle-aged (30-59 years) adults without prevalent CVD from the National Health and Nutrition Examination Surveys 2015-18, continuous 10-year (10Y) and 30-year (30Y) HF risk estimates were calculated using short- and long-term risk equations derived in the Cardiovascular Lifetime Risk Pooling Project. High estimated 10Y risk was classified as ≥5%, and high 30Y risk as ≥20%. Participants were categorized by combined 10Y and 30Y estimated risk categories overall and stratified by sex, race, age, and body mass index. Distributions were compared using chi-square tests.

Results:
In 1495 NHANES participants (representing 53,022,413 Americans) with mean age 45 years (SE 0.3), median 10Y risk was 0.8% and 30Y risk was 11%. Approximately 4% of individuals were estimated to have high 10Y predicted risk of HF. Of those who were classified as low 10Y risk, 23% had high 30Y predicted risk. Distributions differed significantly by sex, race, age, and BMI (P<0.01,
Figure
). Black males more frequently were classified as high 10Y or 30Y risk compared to other race-sex groups. Older individuals and those with BMI ≥30 kg/m
2
had a higher frequency of low 10Y but high 30Y risk.

Conclusions:
More than one-fourth of middle-aged U.S. adults have elevated short- or long-term predicted risk for HF. While the majority of middle-aged US adults are at low 10Y risk for HF, a large proportion among this subgroup are at high 30Y HF risk. Application of both short- and long-term HF risk prediction may mitigate the growing morbidity and mortality related to HF and identify strategies to target those at-risk earlier in the life course.
Abstract 15429: One-year Patterns of Home Blood Pressure Monitoring Using Consumer-purchased Wireless Devices in the Health Eheart Study
Authors: Zheng Yaguang , Zhang Yanfu , Huang Heng , Tison Geoffrey H , Burke Lora E , Olgin Jeffrey , Marcus Gregory M , Pletcher Mark J
Published: November 2020

Introduction:
Engagement with home blood pressure monitoring (HBPM) usually declines over time; however, published studies have not described inter-individual variability of HBPM behaviors. We aimed to describe different 1-year patterns of HBPM behaviors, identify predictors of those patterns, and examine the association of HBPM behaviors with BP levels over time.

Methods:
We analyzed BP records from the Health eHeart (HeH) Study, an ongoing prospective e-cohort study, limiting our analysis to participants with a wireless consumer-purchased device that transmitted date-and time-stamped BP data to the HeH server through a full 12 months of observation starting from the first day they used the device. Participants received no instruction on device use. We applied clustering analysis to identify 1-year HBPM patterns.

Results:
The sample (N=2099) had a mean age of 52.0±12.0 years and BMI of 28.9±6.5 kg/m
2
; most were male (89.1%) and White (88.6%). Using clustering algorithms, we found that a model with three patterns fit the data well (Figure); 69.7% were Sporadic Users, 21.2% were Weekly Users, and only 9.1% were Daily Users. Daily Users were older, unemployed, lower income, and more likely to have diabetes, coronary heart disease, and a history of myocardial infarction (p<.05 for all). Daily Use was also associated with lower BP levels that remained persistently lower than the Weekly or Sporadic Users throughout the year (estimated mean ± standard error, respectively: SBP: 126.2±0.8 vs.128.8±0.5 vs.128.3±0.3, p=.036; DBP: 76.3±0.6 vs. 80.2±0.4 vs. 79.9±0.2, p<.001).

Conclusion:
We identified 3 distinct HBPM use patterns, with nearly 10% sustaining a daily use pattern that was associated with lower BP levels despite being in socially and medically higher risk groups.