bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11780: Longitudinal Echocardiographic Parameters Before and After Pacemaker Placement in Congenital Complete Heart Block
Authors: Weinreb Scott J , Ampah Steve , Okunowo Oluwatimilehin , Griffis Heather M , Vetter Victoria L
Published: March 2022

Introduction:
Congenital complete heart block (CCHB) is rare, 1:15,000 - 1:20,000 live births, with left ventricular (LV) dysfunction developing in 7-14% of subjects. We investigate longitudinal trajectories of echo parameters in CCHB and the effect of pacemaker implantation on those parameters.

Methods:
This is a retrospective cohort study of identifiable CCHB subjects at the Children’s Hospital of Philadelphia from 1970-2018, excluding those with structural, genetic, or acquired cardiac conditions. Subjects with echo data available before and after pacemaker implantation are included. LV end diastolic diameter (LVEDD) z-score and LV ejection fraction (EF) are modeled with least-squares regression models, with slopes compared before and after pacemaker placement.

Results:
Of 114 subjects with CCHB, 52 (40% male, 73% white) have echo data available before and after pacemaker placement. Median age of diagnosis is 0.6 years, age at pacemaker placement 3.4 years, and duration of pacing 10.8 years. Figure 1 displays modeled trajectories of LVEDD z-score and EF over 20 years. Mean LVEDD z-score at pacemaker placement is less than 2 and decreases significantly over time, especially 10 years post placement. Participants have mean LV ejection fraction of 54% at pacemaker placement, rising significantly prior to placement and in the first 10 years post-placement, after which significant decreases are observed. Older age at pacemaker placement is associated with a higher EF at placement but an earlier and steeper decline in EF beginning at 8 years post-placement. LVEDD and EF trajectories do not vary significantly by sex, race, maternal antibody status, age at diagnosis, or initial pacemaker mode.

Conclusions:
In a cohort of 52 subjects with CCHB, LVEDD z-score steadily decreases over time whereas EF rises for 10 years post-pacemaker placement and subsequently decreases. Pacemaker placement has no apparent immediate effect on trajectories of these echo parameters.
Abstract 11799: The Direction and Magnitude of Cardiac Contractile Motion: Considerations for Stereotactic Radio-Ablation of Ventricular Tachycardia
Authors: Wu Bryan , Vanam Sai , Atwood Todd , Bruggeman Andrew , Moore Kevin , McVeigh Elliot , Han Frederick , Hsu Jonathan C , Hoffmayer Kurt S , Raissi Farshad , Birgersdotter-green Ulrika , KARUNAMUNI JENNIFER , STARK PAUL , Feld Gregory K , Mundt Arno , Krummen David , Ho Gordon
Published: March 2022

Introduction:
Stereotactic ablative radiotherapy is an emerging therapy for ventricular tachycardia (VT), but it is unknown whether its precision may be limited by cardiac motion from the beating heart.

Hypothesis:
The magnitude of cardiac contractile motion may vary between patients and across different directions in 3D.

Methods:
Patients who underwent 4D cardiac computed tomography (4DCT) prior to a catheter ablation procedure for atrial or ventricular arrhythmias at 2 medical centers were studied retrospectively. 4DCT was acquired using cardiac-gated Siemens Force or GE Revolution scanners. The displacement of transvenous right atrial (RA) and right ventricle (RV) ICD lead tips across the cardiac cycle (divided into 10 time phases) were measured in orthogonal 3D views on a maximal-intensity projection CT reconstruction (Fig 1) using imaging analysis software (Horos Project). Displacement was compared using 1-way ANOVA.

Results:
In 14 patients (age 65±11.7 years), contractile motion along the left-right axis, craniocaudal axis, and anteroposterior axis were significantly different for both the RV (0.7±0.4, 0.4±0.2, 0.4±0.2cm, p=0.017) and RA (0.7±0.5, 0.4±0.2, 1.1±0.7cm, p=0.008). The greatest variability between patients in the displacement of the RV lead tip was along the left-right axis (range 0.16cm to 1.52cm) and of the RA lead tip was along the anteroposterior axis (0.2cm to 2.3cm). Clinical characteristics (i.e. ejection fraction) were not associated with the magnitude of motion.

Conclusions:
Contractile motion was greatest in the left-right direction in the ventricle (up to 1.52cm), but there was a large variation in motion between patients (ranging up to 1.4cm). The magnitude of contractile motion should be assessed on a patient-specific basis. Further studies are underway to develop optimal strategies to account for contractile motion, such as patient-tailored planned target volume expansions and cardiac-gated radiotherapy delivery.
Abstract 11800: Inhibition of Pyruvate Dehydrogenase Kinase Does Not Improve Cardiac Abnormalities in a Mouse Model of Human Barth Syndrome
Authors: Greenwell Amanda A , Saed Christina T , Gopal Keshav , Tabatabaei Dakhili Seyed Amirhossein , Kruger Jennifer , Eaton Farah , Lopaschuk Gary D , Oudit Gavin Y , Ussher John R
Published: March 2022

Introduction/Hypothesis:
Heart failure presents as the leading cause of infant mortality in individuals with the rare genetic disease, Barth Syndrome (BTHS). The causative mutation underlying the BTHS phenotype has been mapped to the tafazzin (
TAZ) g
ene, which encodes for a phospholipid transacylase critical for the remodelling of the mitochondrial phospholipid, cardiolipin. Perturbations in myocardial energy metabolism may contribute to the development and progression of cardiomyopathy in BTHS. Given that cardiac glucose oxidation is impaired in a mouse model of human BTHS, we hypothesized that pharmacological enhancement of glucose oxidation through dichloroacetate (DCA) treatment could mitigate BTHS-related cardiac dysfunction.

Methods:
DCA was added to the drinking water (84 mM) of 6-week-old mice with experimental BTHS (doxycycline-inducible
Taz
knockdown (TazKD) mice) for 6-weeks.
In vivo
cardiac function was assessed via ultrasound echocardiography prior to and following the DCA treatment period. Hearts were extracted from TazKD mice and their wild-type (WT) littermates for protein expression profiling and enzyme activity assessment at the end of the treatment protocol.

Results:
Prior to treatment at 4-5 weeks of age, TazKD mice exhibited hypertrophic cardiomyopathy as demonstrated by an increase in the ratio between left ventricular (LV) anterior and posterior wall thickness during diastole in relation to lean body mass (0.042±0.003 vs 0.062±0.008 mm/g; 0.049±0.002 vs 0.069±0.005 mm/g). TazKD mice also exhibited impaired LV systolic and diastolic volumes. Treatment with DCA decreased inhibitory phosphorylation of pyruvate dehydrogenase, the rate-limiting enzyme of glucose oxidation, and trended to increase its activity (
p
=0.19) in ventricular extracts from TazKD mice compared to their WT littermates, thus suggestive of increased myocardial glucose oxidation. However, despite a potential improvement of cardiac energy metabolism, treatment with DCA did not improve cardiac structural and functional parameters in TazKD mice.

Conclusions:
Our findings suggest that optimization of cardiac glucose oxidation may not be a feasible strategy for alleviating BTHS-associated cardiomyopathy.
Abstract 11808: Direct Oral Anticoagulant Use in Preventing Ischemic Stroke in Patients With Left Ventricular Thrombus
Authors: Skaf George , Daftari Diana , gelman samantha , Savoj Javad , Ayutyanont Napatkamon , Biswas Mimi S
Published: March 2022

Background:
Left Ventricular thrombus are commonly associated with systolic heart failure and acute myocardial infarctions. It is thought to be associated with an increased risk of embolic events. Current guidelines recommend the use of Warfarin for these patients. Off label use of Direct Oral Anticoagulants (DOAC) for these patients are becoming increasingly frequent as Warfarin may be inappropriate for many of these patients. DOACs have already been shown to be advantageous to warfarin in the treatment of pulmonary embolisms, deep vein thrombosis, non-valvular atrial fibrillation and is even now being looked at some instances of valvular atrial fibrillation with updated mechanical valves.

Methods:
This is a retrospective study on patients diagnosed with a Left Ventricular thrombus discharged on a DOAC versus warfarin looking for ischemic stroke admissions, length of stay and comparing severities of stroke using NIHSS controlling for demographic, comorbid conditions, ED and ICU admissions. Data was collected from 144 HCA hospitals.

Results:
There were 1704 patients in the warfarin group and 2210 in the DOAC group. There was no statistically significant difference in the odds of being readmitted for ischemic stroke by DOAC compared to warfarin (OR=1.08, [95% CI (0.82, 1.44)], p=0.582). Patients discharged on DOAC had a 81% lower odds of being readmitted within 30 days compared to warfarin (OR=0.19, 95%CI [0.05, 0.76], p = 0.019). The patients with left ventricular thrombus discharged on warfarin showed a higher average length of stay (8.21 ± 9.73) compared to DOAC (6.35 ± 7.61) (p < .001). There was no statistically significant differences in the NIHSS scores by discharge medications (warfarin vs. DOACs, p=0.340).

Conclusion:
Our study showed no statistically significant difference in using DOAC’s compared to warfarin, the standard of care, in preventing a stroke in patients with a left ventricular thrombus. We were also able to show a decreased readmission rate, a decreased length of stay and no difference in the severity (NIHSS) of stroke. If this data holds true many patients and physicians will chose DOACs over warfarin to improve medication compliance, dosing burden and potential adverse drug interactions.
Abstract 11814: Definitive Diagnostic Yield in a Referral Population is Similar to That of Cascade Genetic Screening
Authors: Aryan Zahra , Nascimben Julia , Macrae Calum A
Published: March 2022

Introduction:
We aimed to investigate the prevalence of a definitive diagnosis among those who were referred for assessment of a suspected inherited cardiovascular disorders (CVD) compared to cascade screening.

Methods:
A retrospective cohort study was conducted in an adult cardiovascular genetics referral center from 2015 to 2021. Data on initial manifestations, family history, laboratory results, ECG, echocardiogram, cardiac MRI, genetic testing, treatment, and clinical outcome was extracted. Participants were categorized as; 1) definitively diagnosed; individuals who met the diagnostic criteria of a specific inherited CVD 2) overlap diagnosis: individuals with abnormal phenotypes or a positive definitive genetic finding who failed to meet the diagnostic criteria of a certain inherited CVD, and 3) normal: individuals in whom there was no objective evidence of an inherited CVD. The yield of definitive diagnosis for those who were referred for assessment of a suspected inherited CVD (referred group) was compared with proband-initiated cascade screening.

Results:
A total of 503 patients (51.5% female, mean age of 43 years) with 1153 person-years follow up were studied. Of these individuals, 174 (34.6%) were seen for cascade screening. After comprehensive evaluation a definitive diagnosis of an inherited CVD was made in 202 (40.1%), 187 (37.2%) were effectively normal and 114 (22.6%) were in the overlap diagnosis category. There was no significant difference in the yield of definitive diagnosis in the referred group when compared to those assessed during cascade screening (39.7% vs. 40.4%, p=0.86).

Conclusions:
The proportions of definitive diagnoses and overlap diagnoses are similar in comprehensive CVD genetic evaluations whether referred on the basis of physician suspicion or screened due to relatedness to definitive probands. These data suggest that current inherited CVD syndrome definitions are incomplete and may lead to errant misclassification.
Abstract 11832: Activated Cardiomyocytes in the Cell Cycle Promote Cardiac Engraftment
Authors: Kasamoto Manabu , Yoshida Yoshinori , Funakoshi Shunsuke , Hatani Takeshi , Kimura Takeshi , Okubo Chikako
Published: March 2022

Rationale:
The only treatment for drug-resistant heart failure is heart transplantation, however, it has problems such as donor shortages and rejection. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-cardiomyocytes) are promising sources of regenerative medicine that can solve these problems. The engraftment potential of hiPSC-cardiomyocytes following the transplantation into the host heart should be improved to realize this therapy.

Objective:
We aim to discover a compound to enhance the engraftment of hiPSC-cardiomyocytes following the cell transplantation into the damaged heart. We also aim to realize a larger graft size and recover cardiac function.

Methods and Results:
We established an iPSC line constitutively expressing Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI), which can show the cell cycle phase in real-time. We compared the engraftment capacity of hiPSC-cardiomyocytes in between the S/G2/M (activation) phase and G0/G1 (inactivation) phase for three months after transplantation, finding cell cycle activated hiPSC-cardiomyocytes showed significantly higher engraftment efficiency than those in inactivated. We, thus, conducted the screening to find cell-cycle activating compounds in the hiPSC-cardiomyocytes. The screening identified some candidates from more than 4000 compounds, and we focused on the most effective compound (CCA-1). An EdU assay and cell number count demonstrated the activation of proliferative capacity by CCA-1. Moreover, genetic analysis revealed a group of genes related to CCA-1-induced cell cycle activation. Finally, using in vivo bioluminescent imaging, we confirmed that CCA-1 treated hiPSC-cardiomyocytes showed enhanced graft size after transplantation into mice ischemic heart.

Conclusions:
This study highlights the effectiveness of the FUCCI system to analyze the cell cycle status in hiPSC-cardiomyocytes, and the cell cycle activation by CCA-1 is the efficient strategy to increase the graft size following the cell transplantation into the damaged heart.
Abstract 11843: Population Effects of Clinical, Laboratory, and Genetic Risk Factors for Incident CAD: A Cohort Study in the UK Biobank
Authors: Marnell Christopher S , Bhattacharya Romit , Zekevat Seyedeh M , Trinder Mark , Honigberg Michael , Peloso Gina , Natarajan Pradeep
Published: March 2022

Background:
Modifiable clinical risk factors are estimated to account for the majority of population attributable risk (PAR) for first myocardial infarction (MI).

Hypothesis:
Novel biomarkers and genetic factors additionally contribute to the risk for first MI.

Methods:
We determined incident coronary artery disease (CAD), defined as first-time MI or revascularization, in the UK Biobank. Exposures included laboratory (ApoB/A1, lipoprotein(a) [Lp(a)], C reactive protein [CRP]), genetic (CAD polygenic risk score [PRS], heterozygous familial hypercholesterolemia [HeFH]), and clinical (waist/hip ratio, hypertension, diabetes, diet, exercise, smoking, Townsend deprivation index) risk factors. We fitted multivariable logistic regression models with clinical risk factors alone, then added CAD PRS, HeFH, CRP and Lp(a).

Results:
Among 98 387 participants, 5 408 had incident CAD (5.5%). Compared to a model with clinical risk factors alone (PAR 82.3%, 95% CI 77.6-86.9%), adding novel biomarkers (Lp(a), CRP) and genetic risk raised total PAR to 89.0% (95% CI 86.4-91.5%). Novel risk factors Lp(a) > 125 nmol/L (OR 1.22, PAR 2.5%), CRP > 2.0 mg/L (OR 1.22, PAR 8.0%), HeFH (OR 1.52, PAR 0.1%), and high CAD PRS (OR 2.48 for top vs lowest decile, PAR 37.4%) were significantly associated with incident CAD controlling for clinical risk factors. In combination with novel risk factors, smoking (OR 1.25 for current + former vs never, PAR 11.3%), ApoB/A1 ratio (OR 1.60 for top vs lowest quintile, PAR 16.6%), hypertension (OR 2.17, PAR 31.9%), waist-to-hip ratio (OR 1.21 for top vs lowest tertile, PAR 13.3%), diabetes (OR 1.59, PAR 5.6%), diet (OR 1.42, PAR 7.8%), exercise (OR 1.12, PAR 7.1%) and Townsend index (OR 1.34 for top vs lowest decile, PAR 8.6%) were significantly associated with incident CAD at α=0.05.

Conclusions:
The novel cardiovascular risk factors Lp(a), CRP, CAD PRS, and HeFH contribute significant risk for first-time CAD, with PAR for CAD PRS exceeding conventional risk factors.
Abstract 11847: Acute Myocarditis Following COVID-19 mRNA Vaccination
Authors: Simone Anthony , Herald John , Chen Aiyu , Gulati Neil , Shen Albert Yuh-Jer , Lewin Bruno , Lee Ming
Published: March 2022

Introduction:
Acute myocarditis after coronavirus disease 2019 (COVID-19) mRNA vaccination is not well described. Recent public reports have signaled that this is an entity that requires ongoing surveillance. The goal of this study is to investigate myocarditis incidence following COVID-19 mRNA vaccination, and to report the clinical course and outcomes.

Methods:
This is a retrospective population-based cohort study performed at Kaiser Permanente Southern California (KPSC), an integrated health care system in California. Patients who received at least one dose of BNT162b2 (Pfizer) or mRNA-1273 (Moderna) mRNA vaccine were included. Clinically significant cases of acute myocarditis within 10 days of COVID-19 mRNA vaccination were identified between 12/14/2020 and 5/31/2021. Key demographic, clinical, laboratory, diagnostic data, and clinical course were obtained from medical record review.

Results:
Of 1,776,608 KPSC members who received at least one dose of COVID-19 mRNA vaccines, 12 developed acute myocarditis within 10 days following vaccination, for an estimated incidence of 6.6 cases per 1 million patients. All patients were relatively healthy White or Hispanic men between the ages of 18 and 40 years. Patients reported chest pain two to eight days after vaccine administration (Moderna N=5; Pfizer N=7). Eleven patients developed myocarditis after the second dose, and one after the first dose. Troponin I elevations ranged from 1.53-32.30 ng/mL. All cases were self-limited, with troponin peaking within 24-48 hours of admission and symptom resolution prior to discharge. None of the patients had evidence of decompensated heart failure. Length of stay was 1-4 days, with all patients discharged home and no recurrence, readmission, or major adverse cardiac events.

Conclusions:
Acute myocarditis after COVID-19 mRNA vaccination is a rare and self-limited event that warrants further description and investigation.
Abstract 11850: Targeted Next-Generation Sequencing of 36 Lipid-Related Genes in Patients With Clinically Diagnosed Familial Hypercholesterolemia
Authors: Okada Takeshi , Koseki Masahiro , Nishida Makoto , Omatsu Takashi , Tanaka Katsunao , Inui Hiroyasu , Chang Jiuyang , Kanno Kotaro , Saga Ayami , Ohama Tohru , Ishihara Mitsuaki , Kujiraoka Takeshi , Hattori Hiroaki , Masuda Daisaku , Yamashita Shizuya , Sakata Yasushi
Published: March 2022

Background:
Familial hypercholesterolemia (FH) is characterized by elevated serum low-density lipoprotein cholesterol (LDL-C) levels and premature coronary artery disease. This condition is considered to be caused by mutations of conventional FH genes such as LDL receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). However, it is not fully elucidated whether other lipid-related gene variants may be overlapped in addition to these FH genes.

Methods and Results:
One hundred twenty-five heterozygous FH (HeFH) patients in Osaka University Hospital and Rinku General Medical Center, who met the clinical FH criteria of Japan Atherosclerosis Society were enrolled. Genomic DNA for each patient was extracted from peripheral blood cells. Targeted exon sequencing was performed to investigate 36 lipid-related genes including conventional FH genes. Among variants with a minor allele frequency of <5% in 1000 Genomes Project of East-Asian population, we have defined pathogenic variants if they fulfilled i) protein truncating variants, ii) damaging missense variants, and iii) ClinVar-registered pathogenic or likely pathogenic variants. Among 125 HeFH patients, we have identified LDLR pathogenic variants in 89 patients (71.2%), PCSK9 variants in 6 patients (4.8%), and APOB variants in 1 patient (0.8%). Among these 96 patients, 37 patients (38.5%) additionally have pathogenic variants of other lipid-related genes, which include apolipoprotein E2 (APOE2) in 3 patients, apolipoprotein E4 (APOE4) in 19 patients, variants of ATP-binding cassette subfamily G member 5 (ABCG5) in 3 patients, apolipoprotein C3 (APOC3) in 1 patient, and CD36 in 11 patients. As for remaining 29 patients without conventional FH gene variants, 17 patients (58.6%) have pathogenic variants of other lipid-related genes, which include APOE4 in 13 patients, apolipoprotein E5 (APOE5) in 1 patient, variants of ABCG5 in 1 patient, and CD36 in 2 patients.

Conclusion:
Approximately 40% clinically diagnosed HeFH patients have pathogenic variants of other lipid-related genes in addition to those of conventional FH genes. These overlapping variants may affect the atherogenicity of patients and selection of medication.
Abstract 11854: Longitudinal Improvement in Patient Reported Outcome Measures Following Supervised Exercise Therapy for Symptomatic Peripheral Artery Disease
Authors: Chowdhury Mohsin , Natesan Sahana , Schmaier Alec , Raja Aishwarya , Carroll Brett , Krawisz Anna , Rose Betsy , Secemsky Eric A
Published: March 2022

Background:
Symptomatic peripheral artery disease (PAD) is associated with severe morbidity and poor quality of life. Although data suggest that supervised exercise therapy (SET) may improve symptoms, few studies have evaluated longitudinal changes in patient reported outcomes among a real-world PAD population.

Methods:
Consecutive patients with symptomatic PAD treated at a single tertiary care center and referred for SET were enrolled. Patient reported outcomes were assessed at baseline and at 30 days, 6-months, and 1-year post-treatment through an electronic survey. The primary outcome was the change in the Peripheral Artery Questionnaire (PAQ) summary score from baseline to each time point. A change in PAQ summary score of >8 has been established as clinically meaningful improvement.

Results:
Twenty-nine patients enrolled in the study received SET who had a mean baseline PAQ score 46.9±16.5. Following treatment, the mean PAQ score at 30 days, 6 months and 1 year were 61.0 ±20.7, 70.4 ±16.2 and 67.0 ±13.9, respectively (Figure 1), corresponding to a 14.1 point, 23.5 point and 20.1 point improvement in PAQ score.

Conclusion:
In this real-world assessment of patient reported outcomes following SET for the management of symptomatic PAD, treatment demonstrated consistent long-term improvement in patient reported outcomes as measured by the PAQ. Future work assessing the long-term durability of these changes is ongoing.
Abstract 11857: Benchmarking a Functional Assay to Assist Clinical Classification of Variants of Uncertain Significance in
KCNH2
(Long QT Syndrome Type 2)
Authors: Jiang Connie , Farr Jessica , Hill Adam , Kroncke Brett , Ingles Jodie , Vandenberg Jamie , Ng Chai A
Published: March 2022

Introduction:
Our ability to determine the pathogenicity of variants is limited by the paucity of clinical data when variants are seen in very few individuals. In vitro functional assays could help overcome the deluge of variants of uncertain significance (VUS). To be clinically useful, such assays must satisfy stringent benchmarking criteria established by the ACMG/AMP. For variants in
KCNH2
, the cause of Long QT Syndrome Type 2 (LQTS2), ~70% of missense variants are VUS. Here, we wish to formally evaluate the accuracy, replicability and robustness of a high-throughput automated patch-clamp (APC) assay for characterising
KCNH2
variants.

Aim:
To evaluate an APC assay for
KCNH2
variants against the criteria for the application of functional evidence within the ACMG/AMP framework.

Methods:
Twenty five variants classified as pathogenic/likely pathogenic and 18 variants classified as benign/likely benign from ClinVar were heterozygously expressed in stable Flp-In HEK293 cells and analysed for loss-of-function based on current density and changes in channel gating.

Results:
Twenty three of 25 pathogenic variants had <50% wild-type (WT) peak current density, indicating loss-of-function. The two remaining pathogenic variants, G584S and N629S, had <50% WT current levels (IKr) after incorporating additional gating measures. All 18 benign variants had >50% WT current levels both before and after including gating measures. For 17 of the benign variants, current levels were not statistically different to WT. The current level for R148W was significantly different to WT (p<0.005) but was still >50%. Based on a 50% cut-off, the assay yields a sensitivity of 100% and specificity of 100%.

Conclusions:
High-throughput electrophysiological phenotyping correctly predicted loss of function for 25/25 pathogenic variants, and 18/18 benign variants. The assay should be able to assist with the clinical classification of
KCNH2
variants.
Abstract 11860: Long Term Outcomes and Risk Stratification in Patients With Heart Failure With Recovered Ejection Fraction
Authors: Perry Andrew , Mudigonda Parvathi , Huang Gary , Cheng Richard , Levy Wayne C , Li Song
Published: March 2022

Introduction:
Data are lacking on the natural history of heart failure with recovered ejection fraction (HFrecEF) with no available risk model for future heart failure events. This study aimed to understand the long-term outcomes of patients with HFrecEF, identify predictors of adverse events, and develop a risk stratification model.

Methods:
From an academic healthcare system we retrospectively identified patients who had an improvement in left ventricular ejection fraction (LVEF) from <40% to ≥53%. Significant predictors of all-cause mortality, hospitalization and recurrent reduction in LVEF were identified via Cox regression analysis. A Cox proportional hazard risk model was developed for all-cause mortality.

Results:
133 patients were included (median age 67, 39% female, 30% ischemic etiology). Kaplan-Meier survival was 70% at 5 years. Freedom from hospitalization was 58% at 1 year, and the risk of recurrent LVEF reduction to <40% was 28% at 3 years. Diuretic dose and BNP at the time of LVEF recovery were the strongest predictors of mortality and hospitalization in multivariate adjusted analysis (BNP HR per 100pg/mL increase 1.13 [p<0.01]; furosemide equivalent dose HR per 40mg increase 1.19 [p=0.02]). An all-cause mortality risk model incorporating NYHA functional class, BNP and diuretic dose at the time of recovery showed excellent risk discrimination (c-statistic 0.79) and calibration.

Conclusions:
Patients with HFrecEF have significant heterogeneity in clinical outcomes ranging from persistent recovery to requiring advanced heart failure therapies or death. A risk model utilizing NYHA functional class, BNP and diuretic dose can accurately stratify mortality risk.
Abstract 11865: New Insights Into Optimal Duration of Dual Antiplatelet Therapy After Left Main Coronary Stenting: Findings From the Largest LM PCI Cohort
Authors: Wang Haoyu , Xu Bo , Zhang Rui , Guan Changdong , Dou Kefei
Published: March 2022

Background:
The optimal duration of dual antiplatelet therapy (DAPT) and the risk-benefit ratio for long-term DAPT in patients with left main coronary artery disease (LMCAD) undergoing PCI remains uncertain.

Objectives:
The aim of this study was to assess the efficacy and safety of extended duration DAPT (>12-month) versus ≤12-month DAPT in patients who received PCI for LMCAD.

Methods:
A total of 4,561 consecutive patients undergoing PCI and stenting of LMCAD at a single center from January 2004 to December 2016 were enrolled. The primary outcome was 3-year MACCE (death, myocardial infarction, stent thrombosis, or stroke). The key safety outcome was BARC 2, 3, or 5 bleeding at 3 years.

Results:
3,865 patients free of major ischemic or bleeding events in the first 12 months were included in the primary analysis. The distal LM bifurcation disease was involved in 80.5% of cases, in whom 27.0% were treated with a 2-stent strategy. DAPT>12-month (n=1,727) versus ≤12-month DAPT (n=2,138) was associated with a reduced risk of 3-year primary outcome (2.5% vs. 4.5%; adjusted HR [aHR]: 0.592, 95% CI: 0.414-0.948). Similar results were found for the other ischemic end points: all-cause mortality (0.9% vs. 3.0%; aHR: 0.315 [0.179-0.554]), cardiovascular mortality (0.5% vs. 1.6%; aHR: 0.354 [0.169-0.739]), myocardial infarction (0.8% vs. 1.9%; aHR: 0.451 [0.245-0.831]), and stent thrombosis (0.4% vs. 1.1%; aHR: 0.400 [0.171-0.936]). Long-term DAPT showed similar risks of BARC 2, 3, or 5 bleeding compared to short-term DAPT (1.8% vs. 1.6%; aHR: 1.109; 95% CI: 0.681-1.806). The lower risk of a net adverse clinical event (a composite of BARC 2, 3, or 5 bleeding and MACCE) was identified in patients in patients treated with extended-term DAPT (4.1% vs. 5.7%; aHR: 0.729; 95% CI: 0.543-0.980). The effect of DAPT>12-month on the reduction of primary outcome was consistent across clinical presentations (stable CAD vs. ACS), P2Y
12
inhibitor (clopidogrel vs. ticagrelor), and LM bifurcation PCI (1- vs. 2-stent strategy).

Conclusions:
In a large cohort of consecutive patients undergoing LM PCI, longer DAPT duration (>12 months) could achieve more favorable outcomes by reducing ischemic risk, not significantly offsetting the increases in clinically relevant bleeding events.
Abstract 11868: A Reduced Anticoagulation Strategy Among Patients Supported With Ventricular Assist Device is Not Associated With Increased Mortality
Authors: Shin Soomin , Sheridan Brett , Huang Qiwen , Sudat Sylvia , Pham Michael X
Published: March 2022

Introduction:
Patients with left ventricular assist device (VAD) are typically treated with aspirin and warfarin. However, some patients are unable to tolerate full anticoagulation (AC). There is limited information available regarding intermediate-term outcomes in patients on reduced or no anticoagulation.

Methods:
Patients who underwent VAD implantation at California Pacific Medical Center from January 2015 to January 2020 were studied retrospectively. Patients received aspirin 81 mg daily and warfarin with a target INR of 2-3, and anticoagulation was gradually de-intensified or withdrawn in response to recurrent mucosal bleeding. Pre-implantation characteristics, thrombolytic events (hemolysis, pump thrombosis requiring exchange, TIA, or ischemic CVA), and survival post-implant were compared among patients treated with full AC vs. reduced or no AC. We performed nonparametric survival analysis to obtain Kaplan-Meier survival estimates as of 9/15/2020. Cox proportional hazards regression was used to adjust for confounders measured at baseline.

Results:
91 patients underwent VAD implant (80 HeartMate 3 and 11 HeartMate II). The median age was 65, and the majority of patients (79%) were treated as destination therapy. Reduced AC was used in 43 patients (47%), including no anticoagulation (12 patients), aspirin monotherapy (2 patients), warfarin monotherapy (16), warfarin monotherapy with a reduced INR target (10), and aspirin plus warfarin with a reduced INR target (3). During a median follow-up of 22 months, 15 thrombotic events were observed (12 in the reduced AC group and 3 in the full AC group, P=0.19). Two patients underwent pump exchange. 67% of thrombotic events and both pump exchanges occurred in HMII recipients. Survival was similar in both groups (Figure).

Conclusions:
The use of a reduced or no anticoagulation strategy after VAD implant is not uncommon and is associated with acceptable outcomes, particularly among HeartMate 3 recipients.
Abstract 11871: Left Ventricular End Diastolic Diameter as a Predictor of Severe Functional Mitral Regurgitation Persistence Following Acute Heart Failure Hospitalization
Authors: Rahgozar Kusha , Hase Christopher , Kataria Rachna , MADAN Shivank A , Latib Azeem , Jorde Ulrich P
Published: March 2022

Introduction:
The phenotype of patients with functional mitral regurgitation (fMR) is broad. We sought to study the relationship of left-ventricular end-diastolic diameter (LVIDd) with severe fMR persistence after acute heart failure hospitalization.

Methods/Results:
We conducted a retrospective chart review of consecutively admitted patients to Montefiore Medical Center between 2012-2017 for acute-decompensated heart-failure (ADHF) who also had a severe fMR on index transthoracic-echocardiogram (TTE), and had follow-up TTE available within 1-6 months of hospital discharge. Patients were categorized into two subgroups based on whether their follow-up TTE showed improvement in fMR severity to moderate/less vs. persistence of severe fMR and compared for baseline characteristics. Relationship between LVIDd quartiles based on LVIDd on index TTE, and rates of persistent severe fMR on follow-up TTE were also evaluated. A total of 134 patients met our study criteria, n= 53(40%) with improved fMR and n=81(60%) with persistent severe fMR on follow-up TTE. The two groups were similar including guideline-directed-medical-therapy (GDMT) and diuretic use (Table-1). Patients in the highest LVIDd quartile (≥6.4cm) were less likely to have fMR improvement on follow-up TTE than patients in the 1
st
-3
rd
quartiles (19% vs 46%,p=0.007, Figure 1).

Conclusions:
LVIDd on index TTE at time of ADHF-hospitalization was associated with severe fMR persistence post-discharge. In our cohort, LVIDd ≥6.4cm was associated with lower likelihood of improvement in severe fMR with pharmacotherapy alone, and may help to identify patients who may benefit from interventional therapies.
Abstract 11885: An App That Brings Guidelines to the Point-of-Care: A Pathway for Anticoagulation in Prosthetic Heart Valves
Authors: Kansara Tikal , Saperstein Yair , Park Joongheum , Kumar Ashish , Majmundar Monil , Thakkar Samarthkumar J , Mushiyev Savi , Kokkirala Aravind , Basman Craig
Published: March 2022

Introduction:
AHA/ACC guidelines are updated regularly, but their clinical implementation at bedside or in the clinic is cumbersome, complicated, and difficult. Apps may fill this gap by bringing medical guidelines to the physician at the bedside. We built the AHA/ACC guidelines as an interactive app that makes the guidelines accessible at the point-of care. This app, in turn, saves time, increases efficiency, and improves the quality of care.

Method:
While reviewing the AHA/ACC guidelines, we realized that several unique flowcharts can be created each with endpoints being the recommendation for a specific patient characteristic. We used Google App Script and build a spreadsheet-based branching-tree questionnaire with data entry points (e.g., segmented buttons, text data field, or multiple-item selectors) for data inputs. Our data inputs were based on the most recent AHA/ACC guidelines. A unique trigger was set to each data entry item, allowing branching of questions and the users being exposed to a specific subset of questions at each selection. On completion of the clinical module, the app script packages the contents into multiple CSV files (dashboard, pages, contents of each page, and references), and sends the files to Google Firebase, which is Google’s real-time database. In the end, the final recommendation presented is the specific section of the AHA/ACC guideline pertaining to the characteristics of the patient as entered by the user. Qualitative feedback found our app to be “more usable” than the traditional review of guidelines on the website or a paper printout. A subset of the questions for “anticoagulation in prosthetic heart valve patients” is shown in Figure 1. This example represents one of the many modules designed on the same principle.

Conclusion:
Our interactive app based on AHA/ACC guideline can both save time and improve the quality of care. The app is called “AvoMD”, and we made it available for free on app stores to help clinicians in their practice.
Abstract 11886: Total Root Remodeling by Sleeve Technique for Severe Aortic Regurgitation in Patient With Mild or Moderate Root Dilatation
Authors: Obase Kikuko , Nakaji Shun , Matsumaru Ichiro , Miura Takashi , Eishi Kiyoyuki
Published: March 2022

Introduction:
Cusp repair in combination with root repair is a central strategy for aortic regurgitation (AR). However, aortic root replacement in patient without significant root dilatation is controversial.

Hypothesis:
Sleeve procedure can be an alternative to root replacement in such clinical settings.

Methods:
27 tricuspid aortic valve patients (Body surface area: 1.64±0.16 m2) without significant root dilatation who underwent aortic valve repair with Sleeve procedure during January, 2017-April 2020 were studied. Of the 81 cusps, 34 cusps underwent central plication. Neo-chord technique was prophylactically applied in 12 cusps to prevent future leaflet prolapse. Selected Valsalva graft size was 26.1±1.4 mm. Pre- and post-operative diastolic valve geometry was evaluated by 3D cardiac computed tomography.

Results:
Geometric change in aortic valve by Sleeve is summarized in the Table. Postoperative increase in commissure height was noted and effective height of non-plicated cusp kept more than 8.5 mm in average postoperatively despite of the nearly 10 mm reduction in STJ diameter. There was no recurrence of AR more than grade II in one year follow-up.

Conclusions:
Preserved or increased commissure height by Sleeve procedure may contribute to sufficient cusp coaptation with preventing an iatrogenic cusp prolapse. Because of the external covering with the graft, neo-chord technique could be stably performed under Sleeve procedure. Sleeve procedure offers valve-sparing and total root remodeling without root replacement/coronary reconstruction in repairing AR, which may be beneficial for patients with mild or moderate root dilatation.
Abstract 11893: Women, Ethnic, and Racial Groups Are Underreported and Underrepresented in Atrial Fibrillation Clinical Trials
Authors: Wang Paul C , Rice Eli C , Stafford Randall S , Lewis Eldrin , Wang Paul J
Published: March 2022

Introduction:
Women, ethnic, and racial group representation in clinical trials is low or uncertain in various fields of medicine.

Hypothesis:
Ethnic/racial information is underreported in atrial fibrillation clinical Trials.

Methods:
We systematically reviewed 85 randomized atrial fibrillation clinical trials (RCT), published with results on ClinicalTrials.gov, encompassing 2,546,351 participants from January 2011 to May 2021. We determined the representation of women and ethnic/racial groups, and the frequency of information reporting.

Results:
All of the studies reported gender information; women represented 33.73% of the participants. Only 56.5% (48/75) reported racial/ethnic data. The distribution of the participants were 87% White and 5.1% Black. Data on Latinx were reported in 38% (33/85) of RCTs and represented 5% of reported samples. Only 3.8% of participants were Asian and reported in 34 studies. Ethnic and racial group underrepresentation and underreporting were observed in trials involving device/procedure as well as drug therapy, with more underrepresentation and underreporting observed in drug therapy trials (Table).

Conclusions:
Gender reporting is consistent for all RCTs but with women representing only one-third of participants. However, the ethnic and racial characteristics, particularly in drug therapy trials, are underreported. In RCTs that report ethnic and racial data, Black and Latinx patients are underrepresented compared to their proportion in the overall population. These limitations may significantly impact the generalizability of the RCT results.
Abstract 11896: Building Capacity for a Patient-Centered Research Agenda on Racial and Sex-Specific Cardiovascular Disease Disparities in COVID-19
Authors: Crabbe Deborah L , Hausman Alice , Richardson Briana , Castillo Elyse , Confair Amy , Islam Sabrina , Tajeu Gabriel , Johnson Krys , Gardiner Heather
Published: March 2022

Introduction:
African Americans (AA) and women are under-represented in clinical research. Barriers to including AA’s and women as research partners include fear, distrust, and a poor understanding of the research process. COVID-19 could be an opportunity to engage under-represented minorities and women in the research process.

Objectives:
The goal of this project was to build stakeholder capacity for patient-centered outcomes research (PCOR) and incorporate the perspectives of AA and female patients in developing a research agenda and questions suitable for use in the AHA COVID-19 CVD Quality Improvement Registry (AHA-R). The final research agenda will address the racial/sex-specific CVD disparities in COVID-19.

Methods:
Using community participatory principles, we established a network of stakeholders (AA patients, women, and researchers). Stakeholders were recruited to participate in focus group (FG) interviews and Town Hall (TH) meetings. All activities were held virtually and recorded. Videos and transcripts were independently reviewed. A Research advisory council (RAC, n=8) was recruited from a subset of stakeholders. RAC members received monthly research training using the PCOR Institute’s resources. RAC members attended a training workshop on narrative medicine principles and were encouraged to share their own experiences. The program sponsored 2 Facebook live events and conducted a survey to acquire and share compelling real-life COVID health stories. The questions generated from the FG, TH and RAC were prioritized by the RAC to create a research agenda and questions suitable for inquiry using AHA-R.

Results:
The program educated participants on CVD complications related to COVID (TH =51, 84% AA, 78% women), (FG =28, 93% AA, 82% women). There were 53 questions and 7 compelling narratives generated covering 7 topics. Topics included: COVID with and w/o heart disease, research, COVID and pregnancy, stress, racism, and general heart disease. In both groups, feedback on research results was cited as an important factor for participation in research activities.

Conclusions:
The project developed a research ready stakeholder network, and a prioritized research agenda about CVD disparities in COVID-19 suitable for inquiry using AHA-R.
Left Atrial Volumetric/Mechanical Coupling Index
Authors: Benfari Giovanni , Essayagh Benjamin , Nistri Stefano , Maalouf Joseph , Rossi Andrea , Thapa Prabin , Michelena Hector I. , Enriquez-Sarano Maurice
Published: March 2022

Background:

Left atrial assessment is complex, particularly in heart failure with reduced ejection fraction due to interactions with functional mitral regurgitation (FMR). Pilot data suggest that left atrial volumetric/mechanical coupling index (LACI) may be useful, but large outcome data are lacking.

Methods:

We enrolled a comprehensively characterized cohort of patients in sinus rhythm with heart failure with reduced ejection fraction diagnosis at Mayo Clinic from 2007 to 2011. Routinely measured left atrial volume index and tissue-doppler-imaging a’ allowed LACI calculation as (left atrial volume index)/(tissue-doppler-imaging a’). Survival was the outcome measured.

Results:

The cohort’s 4196 patients (69 [58–77] years, ejection fraction 40 [31–45]%) had mild FMR in 1505 and moderate-severe FMR in 1068. LACI was overall 5.06 (3.50–8.10) and increased with each FMR grade (3.86 [2.94–5.29] without FMR, 5.38 [3.80–8.02] with mild, 5.45 [1.49–8.07] with moderate/severe FMR;
P
<0.0001). At diagnosis, higher LACI was independently determined by more severe FMR and by higher left ventricular mass index, lower ejection fraction, higher E/e’, and lower glomerular filtration rate (all
P
<0.0001). During follow-up 1588 (38%) patients died. In spline modeling, excess mortality appeared around LACI=6 and steeply increased thereafter (5-year survival 72±1% with LACI<6 and 49±2% with LACI ≥6,
P
<0.0001). Multivariable comprehensive adjustment showed LACI strong association with excess mortality (adjusted hazard ratio, 1.41 [1.23–1.61],
P
<0.0001 for LACI ≥6). Independent link to mortality persistent across FMR grades (adjusted hazard ratio, 1.45 [1.13–1.86],
P
=0.004 without FMR, 1.42 [1.16–1.77],
P
=0.0008 with mild FMR, and 1.38 [1.01–1.66],
P
=0.04 with moderate/severe FMR) without interaction (
P
=0.3). LACI independent impact on outcome was incremental to that of left atrial volume index, tissue-doppler-imaging a’, or any other characteristic including the Meta-Analysis Global Group in Chronic-score (least significant
P
=0.02).

Conclusions:

In this large cohort, left atrial volumetric/mechanical coupling measured by LACI in routine practice integrates the influence of several morphological/hemodynamic determinants but displays progressive deterioration with increasing FMR severity in heart failure with reduced ejection fraction. About outcome, higher LACI is strongly, independently, and incrementally associated with excess mortality, irrespective of FMR grade and in all subsets. Hence, LACI is a novel and critical measure in heart failure with reduced ejection fraction, quantifiable in routine practice, which should be integrated in prognostication and decision-making.
Definitions and Clinical Trial Design Principles for Coronary Artery Chronic Total Occlusion Therapies: CTO-ARC Consensus Recommendations
Authors: Ybarra Luiz F. , Rinfret Stéphane , Brilakis Emmanouil S. , Karmpaliotis Dimitri , Azzalini Lorenzo , Grantham J. Aaron , Kandzari David E. , Mashayekhi Kambis , Spratt James C. , Wijeysundera Harindra C. , Ali Ziad A. , Buller Christopher E. , Carlino Mauro , Cohen David J. , Cutlip Donald E. , De Martini Tony , Di Mario Carlo , Farb Andrew , Finn Aloke V. , Galassi Alfredo R. , Gibson C. Michael , Hanratty Colm , Hill Jonathan M. , Jaffer Farouc A. , Krucoff Mitchell W. , Lombardi William L. , Maehara Akiko , Magee P.F. Adrian , Mehran Roxana , Moses Jeffrey W. , Nicholson William J. , Onuma Yoshinobu , Sianos Georgios , Sumitsuji Satoru , Tsuchikane Etsuo , Virmani Renu , Walsh Simon J. , Werner Gerald S. , Yamane Masahisa , Stone Gregg W. , Rinfret Stéphane , Stone Gregg W. ,   On behalf of the Chronic Total Occlusion Academic Research Consortium
Published: March 2022

Over the past 2 decades, chronic total occlusion (CTO) percutaneous coronary intervention has developed into its own subspecialty of interventional cardiology. Dedicated terminology, techniques, devices, courses, and training programs have enabled progressive advancements. However, only a few randomized trials have been performed to evaluate the safety and efficacy of CTO percutaneous coronary intervention. Moreover, several published observational studies have shown conflicting data. Part of the paucity of clinical data stems from the fact that prior studies have been suboptimally designed and performed. The absence of standardized end points and the discrepancy in definitions also prevent consistency and uniform interpretability of reported results in CTO intervention. To standardize the field, we therefore assembled a broad consortium comprising academicians, practicing physicians, researchers, medical society representatives, and regulators (US Food and Drug Administration) to develop methods, end points, biomarkers, parameters, data, materials, processes, procedures, evaluations, tools, and techniques for CTO interventions. This article summarizes the effort and is organized into 3 sections: key elements and procedural definitions, end point definitions, and clinical trial design principles. The Chronic Total Occlusion Academic Research Consortium is a first step toward improved comparability and interpretability of study results, supplying an increasingly growing body of CTO percutaneous coronary intervention evidence.