Circulation, Volume 146, Issue Suppl_1, Page A11773-A11773, November 8, 2022. Background:The impact of recreational marijuana use/cannabis use disorder (CUD) in elderly chronic kideney disease (CKD) patients remains unknown amidst the rising use of cannabis in the USA. We conducted a nationwide study to assess the impact of CUD on cardiovascular outcomes in these patients.Methods:We used National Inpatient Sample (2016-2019) and geriatric (≥65 years) admissions with CKD. We compared baseline characteristics, comorbidities and composite in-hospital outcomes [MACCE- all-cause mortality, acute myocardial infarction-AMI, cardiac arrest and acute ischemic stroke-AIS] between the age-matched (1:1 propensity score matching) CUD+ vs. CUD- cohorts.Results:Age-matched (median 70 years, p=0.998) geriatric CKD-CUD+ (n=34255) and CUD- (n=34225) cohorts were compared. CUD+ cohort often consisted of males (75.0 vs. 53.8%), blacks (35.9 vs 20.8%) and patients from lowermost income quartile (38.7 vs. 33.5%) (p
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Abstract 14592: Impact of Sodium Abnormalities: Hypernatremia vs Hyponatremia on Inpatient Hospital Congestive Heart Failure Outcomes: A National Inpatient Sample Data Analysis
Circulation, Volume 146, Issue Suppl_1, Page A14592-A14592, November 8, 2022. IntroductionSodium abnormalities are commonly associated with congestive heart failure (CHF). The main objective of this study is to analyze the impact of hyponatremia vs. hypernatremia on in-hospital outcomes in patients admitted with CHFMethodsThe National inpatient sample (NIS) data from 2017 to 2018 were queried using International Classification of Diseases 10 (ICD-10-CM) codes E871 and E870. Demographics and hospital characteristics were compared along with In-hospital mortality, length of stay (LOS), and total charge. The outcomes were measured using linear and logistic regression models to adjust the odds ratio for confounders.Results:A total of 350,144 patients with heart failure as a primary diagnosis (42% systolic and 32% diastolic HF) were included in the study. Among them, 37,129 (10.7%) had hyponatremia while 5839 (1.8%) had hypernatremia. In-hospital mortality rates were significantly higher with an adjusted odds ratio (OR) of 2.78 (p
Abstract 9624: Major Adverse Cardiac Events of PCSK9 Modulation by Monoclonal Antibodies vs Small Interfering Ribonucleic Acid Inhibitors. A Meta-Analysis of 92,775 Patients
Circulation, Volume 146, Issue Suppl_1, Page A9624-A9624, November 8, 2022. Introduction:Incliciran, a small interfering ribonucleic acid (siRNA), is the new modulator of the proprotein convertase subtilisin kexin 9 (PCSK9) that has proven safe and effective in reducing LDL-C and ASCVD. However, it is unclear if incliciran is superior to the already established PCSK9 monoclonal antibodies (mAb) in reducing major adverse cardiac events (MACE).Methods:We performed a meta-analysis of randomized controlled trials of patients with high cardiovascular risk who underwent PCSK9 inhibition by either mAb or siRNA. The primary outcome was the reduction of MACE.Results:Thirty RCTs with a total of 92,775 patients were included. For patients with a high cardiovascular risk profile, the modulation of PCSK9 by mAb decreases the risk of MACE (HR 0.84, 95% CI 0.8 – 0.89, p
Abstract 15749: Outcomes of Fluoroless vs. Fluoroscopy-Guided Left Atrial Appendage Electrical Isolation During Catheter Ablation of Atrial Fibrillation
Circulation, Volume 146, Issue Suppl_1, Page A15749-A15749, November 8, 2022. Introduction:Fluoroscopy-guided catheter ablation remains a common practice. With the presence of technologies such as intracardiac echocardiography (ICE) and electroanatomic mapping (EAM), it is possible to perform fluoro- and lead-free procedures to avoid the hazards of prolonged radiation exposure. Left atrial appendage electrical isolation (LAAEI) is a proven e!ective ablation strategy for atrial fibrillation (AF). We sought to assess the characteristics, complications, and outcomes of fluoroscopy-guided LAAEI and compare them to fluoroless LAAEI.Methods:We retrospectively analyzed patients with AF who underwent LAAEI as part of their ablation procedure. The study group included patients who underwent LAAEI either under fluoroscopy guidance or with ICE and EAM alone. We analyzed outcomes and procedural data, including procedural times, fluoroscopy times, radiation exposure (mGy), and radiofrequency times.Results:Overall, we analyzed 168 patients who underwent LAAEI; 110 under fluoroscopy guidance and 58 fluoroless. The mean procedural time was similar in both groups (248 ± 101 vs 264 ± 83 minutes, respectively, p=0.27). The mean RF time was longer in the fluoroscopy-guided group (50 ± 28.2 compared to 43 ± 17.1 minutes, respectively, p
Abstract 14643: Benefits and Risks of Single- vs. Dual- Chamber Implantable Cardioverter Defibrillators for Primary Prevention of Sudden Cardiac Death
Circulation, Volume 146, Issue Suppl_1, Page A14643-A14643, November 8, 2022. Introduction:Implantable cardioverter defibrillator (ICD) is the more effective and safer treatment for the primary prevention of sudden cardiac death. It remains unclear whether dual-chamber ICD offers the clinical benefits over single-chamber ICD without increasing complications.Hypothesis:The study aimed to evaluate the benefits and risks of dual-chamber ICD compared with single-chamber ICD for primary prevention of sudden cardiac death in clinical practice.Methods:Using the Korean National Health Insurance Service database from January 2008 to December 2019, we include patients with primary prevention ICD and no documented indication for pacing. The propensity score matching method was used to balance covariates across single- and dual-chamber ICDs. Primary outcomes were all-cause mortality, hospitalization of heart failure, and hospitalization of cardiovascular cause.Results:Among 1,929 patients, 1,098 (56.9%) received a single-chamber ICD and 831 (43.1%) received a dual-chamber ICD. In 752 pairs of patients after propensity matching baseline characteristics were balanced between the 2 groups (median age 62 years; male 72%). Over a mean follow-up of 2.7±2.4 years, 1- and 5-year all-cause mortality (5.5% vs. 5.6%, P=0.910; 19.4% vs. 19.3%, P=0.948), 1- and 5-year hospitalization for cardiovascular cause (14.9% vs. 14.9%, P=1.000; 23.9% vs. 22.6%, P=0.542), and 1- and 5-year hospitalization for heart failure (10.8% vs. 8.6%, P=0.163; 16.8% vs. 14.0%, P=0.133) were similar in both groups. However, cardiac tamponade in the rates of device-related complications was 0.1% in the single-chamber ICD vs. 1.1% in dual-chamber ICD groups (P=0.013).Conclusions:In the real-world population receiving a primary prevention ICD, dual-chamber ICD was associated with higher rates of cardiac tamponade than single-chamber ICD. One and five-year rates of all-cause mortality and hospitalization did not differ significantly between the two groups.
Abstract 10931: Impact of Atrial Fibrillation Type (paroxysmal vs. Non-paroxysmal) on Long-Term Clinical Outcomes: The Raffine Registry Subanalysis
Circulation, Volume 146, Issue Suppl_1, Page A10931-A10931, November 8, 2022. Background:Type of atrial fibrillation (AF) (paroxysmal or non-paroxysmal) is important for determining the therapeutic management. However, prognostic impact of AF type on incidence of cardiovascular events remains uncertain.Methods:We investigated patients with AF who were selected from an observational, multicenter, prospective registry (RAFFINE) comprising 4 university hospitals and 50 general hospital / clinics in Japan between 2013 and 2015. In this subanalysis of the RAFFINE trial, patients were divided into 2 groups according to their AF pattern at the time of enrollment. The primary outcome was composite of all-cause death, ischemic stroke, and heart failure related hospitalization.Results:Among 3,845 patients, 1,472 (38.3%) and 2,373 (61.7%) were paroxysmal and non-paroxysmal AF, respectively. Patients with non-paroxysmal AF were older, higher CHADS2score and had higher prevalence of comorbidities compared with those with paroxysmal AF. During a median follow-up of 3.7 years, 681 (17.7%) primary endpoints were identified. Cumulative incidences of primary endpoint were significantly higher in non-paroxysmal AF group (log-rank p
Abstract 15753: Comparative Transcriptomics Analysis of Histone (De)acetylases and Cardiac Ion Channels in Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes vs. the Adult Human Heart
Circulation, Volume 146, Issue Suppl_1, Page A15753-A15753, November 8, 2022. Epigenetic regulation is critical for cardiac electrophysiology and pathology. Epigenetic modulators, such as histone deacetylases (HDACs) and histone acetyltransferases (HATs) are known master regulators of gene expression. Recently, novel pharmacological agents, HDAC inhibitors, have been developed as treatments for cancer and immune diseases. The effects of HDAC inhibitors on cardiac ion channels (ICs) are of great interest. To exert specific gene modulation, we used small interfering RNAs against the known HDACs, including sirtuins, and deployed them in human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Follow-up RNAseq data (n = 61) were compared to identically processed and normalized RNAseq data from human left ventricle (LV) from the GTEx database (n = 84). Gene expression of cardiac ICs displayed similar patterns, with some differences. For example, hiPSC-CMs showed upregulatedCACNA1C, SLC8A1and downregulatedKCNJ2andRYR2compared to the adult LV, most of which are known distinctions (Fig. 1A). Correlative analysis (Fig. 1B) and partial least square regression models helped visualize links between HDACs/HATs, key transcription factors (TFs) and cardiac ICs. Powerful TFs, includingMEF2A, GATA4, 6exerted positive effect on ICs in hiPSC-CM and the adult LV. In the hiPSC-CMs,HDAC1, HDAC10andSIRT6were found to be the strongest predictors of the expression of individual cardiac ICs, as revealed by permutation importance. Further studies will involve determination of the role of different cell types using single-cell sequencing data from the adult LV. Our analysis offers new insights about the role of epigenetic modifiers on cardiac electrophysiology and informs the utility of hiPSC-CM as a scalable, experimental model for cardiotoxicity testing of HDAC inhibitors.
Abstract 15119: Diastolic Peak Wall Stresses in Marfan vs Non-Marfan Ascending Thoracic Aortic Aneurysm: A Propensity Score Analysis
Circulation, Volume 146, Issue Suppl_1, Page A15119-A15119, November 8, 2022. Introduction:Marfan syndrome (MFS) carries a risk of aortic dissection and death. The current aneurysm repair guideline of diameter ≥5cm may neglect up to 15% of MFS patients who dissect at smaller diameters. Since dissection can occur biomechanically when wall stress exceeds tissue strength, patient-specific biomechanics may enhance risk stratification for MFS patients. The goal of this study was to compare aneurysm wall stresses between propensity score-matched MFS and non-MFS aneurysm patients.Methods:The cohort consisted of 5 MFS and 42 non-MFS patients with aortic aneurysm. Preoperative CTA or MR scans were used to create 3D hexahedral meshes. Finite element analysis was performed with MFS and nonMFS material properties to determine peak (99th percentile) diastolic stresses[TE1] . Propensity scores were calculated by logistic regression using age, sex, height, hypertension, diabetes, smoking history, valve type, and sinus diameter. Five pairs were formed by 1:1 optimal matching without replacement. Comparisons used the paired t-test.Results:Diameters were similar at the sinus but lower for MFS at the STJ (3.4±0.5 vs 3.9±0.7cm, p=0.003) and the ascending aorta (3.1±0.5 vs 4.3±0.5cm, p
Abstract 9570: Different Distribution of CD163 Positive Macrophages in Thrombus Retrieved From Infarct-Related Artery: Atherothrombosis vs. Cardiogenic Thrombosis, Pathological Analyses From the MITO Study
Circulation, Volume 146, Issue Suppl_1, Page A9570-A9570, November 8, 2022. Introduction:Diagnosis of cardiogenic thrombosis is important because anticoagulant therapy is recommended for its secondary prevention. However, it is difficult to make a clear distinction in the pathogenesis between atherothrombosis and cardiogenic thrombosis.Hypothesis:Role of macrophage in thrombus formation is different between atherothrombosis and cardiogenic thrombosis.Methods:The Macrophage in Thrombus (MITO) study is a prospective observational study examining pathological and biological differences of arterial thrombus between atherothrombosis and cardiogenic thrombosis. Patients with ST elevation myocardial infarction (STEMI) or acute ischemic stroke (AIS) whose solid thrombus could be retrieved from the infarct-related artery were enrolled. Patients were divided into 2 groups as follows; STEMI with sinus rhythm: Group A (presumed atherothombosis) and AIS with atrial fibrillation (presumed cardiogenic thrombosis): Group C, and compared macrophage score as follows; 1:almost no macrophages detected byх40; 2:difficult to detect the macrophages in х20 but detected by х40; and 3:easy to detect macrophages in х20 in the thrombus. Serum levels of soluble CD163 were measured all the patients.Results:The score for CD163 positive macrophage of Group C (n=33) was significantly higher than that of Group A (n=32) (p
Abstract 11462: Alcohol Septal Ablation vs Surgical Myectomy for Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis
Circulation, Volume 146, Issue Suppl_1, Page A11462-A11462, November 8, 2022. Introduction:Surgical Myectomy (SM) is the gold standard treatment for hypertrophic obstructive cardiomyopathy (HOCM). However, alcohol septal ablation (ASA) has emerged as an alternative option for selected patients. Nonetheless, the long-term efficacy and safety of ASA have been debated in recent years. The aim of this metanalysis is to evaluate the long-term outcomes of ASA vs SM in HOCM patients.Hypothesis:ASA is a safe and effective alternative to SM in HOCM.Methods:: Unrestricted searches of the PubMed, EMBASE, and Cochrane databases from inception till June 1, 2022, for studies comparing long-term outcomes of ASA with SM in HOCM patients. Relevant data were extracted and analyzed using Revman 5.3 software. Odds Ratio (OR) and 95% Confidence interval (CI) were calculated using the random-effects model.Results:: A total of 12 retrospective studies were included examining 7,599 HOCM patients (2,010 ASA vs 5,589 SM). After a mean follow-up of 5.04 years, all-cause mortality was similar between the two groups (OR 1.18; 95% CI 0.60-2.29). However, ASA was associated with high rates of reinterventions (OR 15.68; 95% CI 6.71-36.61), and pacemaker insertion (OR 2.74; 95% CI 1.39-5.41).Conclusions:Although there was no difference in mortality between ASA and SM, ASA was associated with higher rates of reinterventions and pacemaker insertion in long-term follow-up. Therefore, the selection of septal reduction therapy in HOCM should be individualized and should be performed in a comprehensive center after detailed risk and benefits discussions with an experienced team.
Abstract 10345: Comparison of Clinical Characteristics, Positive Airway Pressure Usage, and Healthcare Resource Utilization in Obstructive Sleep Apnea Patients With Heart Failure With Preserved vs Reduced Ejection Fraction
Circulation, Volume 146, Issue Suppl_1, Page A10345-A10345, November 8, 2022. Introduction:The prevalence of obstructive sleep apnea (OSA) in heart failure (HF) patients varies from 30 to 50%. The differences in clinical characteristics, healthcare resource utilization (HCRU), and positive airway pressure (PAP) usage between HF with preserved ejection fraction (HFpEF) vs. HF with reduced ejection fraction (HFrEF) in OSA patients are not well known.Objective:To compare clinical characteristics, PAP usage, and HCRU in OSA patients with HFpEF vs HFrEF.Methods:Retrospective cohort study using US administrative claims data linked to objective PAP usage data over one year. HFpEF and HFrEF were identified by ICD-9/10 codes associated with healthcare encounters 1 year before starting PAP therapy. Pearson’s Chi-squared and Wilcoxon rank-sum tests were used as applicable to compare baseline characteristics and PAP usage, and the pre to post-PAP initiation difference in the number of health care encounters.Results:In total, 7,419 patients with HF and OSA were identified, of which 57% had HFpEF. HFpEF patients were majority female (54%) and older than those with HFrEF (64.1 ± 11.52 vs 59.7 ± 11.24 years, p
Abstract 9569: Unplanned Readmission Rate in Tobacco Use Population After Percutaneous Coronary Intervention vs Coronary Artery Bypass Grafting: Propensity Matched Comparison
Circulation, Volume 146, Issue Suppl_1, Page A9569-A9569, November 8, 2022. Introduction:Tobacco use is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD) and associated with cardiac intervention complications. However, there is a lack of data on the effect of smoking status on the post cardiac procedural results.Methods:We conducted a retrospective analysis of the 2018 to 2019 Nationwide Readmission Database (NRD). Adult patients (Age > 18) with tobacco use who underwent either PCI or CABG were selected using the ICD-10-CM diagnosis and procedure code. Discharge-level weight analysis was used to produce a national estimate. Propensity score matching (1:1) with age, sex, and comorbidity burden was performed and the outcomes were compared between matched cohorts.Results:During the study period, 1,392,730 patients underwent PCI (991,730; 71.2%) or CABG (401,000; 28.8%) of which 18,574 patients (1.3%) used tobacco. Patients who underwent PCI with tobacco use were younger (59.7 SE 0.1 vs 62.4 SE 0.2) and with more female population (25.7% vs 18.2%) compared to those who underwent CABG with tobacco use. In discharged patients with tobacco use, unplanned 30-day readmission rate was 9.0%. The majority of the readmission was due to ischemic heart diseases (89.4%) and 2.7% was due to complications of cardiac implants or grafts. A half of readmission occurred within 9 days after the discharge. 9,223 discharged patient with tobacco use who underwent PCI or CABG were propensity-matched. 30-day readmission rate was significantly lower in patients with PCI (8.5% vs 10.7%; p = 0.006). Furthermore, PCI was associated with shorter length of stay (3.5 days SE 0.1 vs 10.1 days SE 0.1; p < 0.001) and lower total hospital cost ($111,492.2 SE 1,188 vs $231,603.6 SE 3,558.3; p < 0.001). In-hospital mortality was similar in PCI and CABG groups (2.0% vs 1.8%, p = 0.26).Conclusions:9.0% of tobacco use patients with ASCVD who underwent PCI or CABG had unplanned readmissions. The most common reason for readmission was ischemic heart disease, with more than 50% of patients returning to the hospital within the first two weeks of hospital discharge. Tobacco use patients who underwent PCI had statistically significantly lower readmission rates, length of stay, than their propensity-matched peers who underwent CABG.
Abstract 12487: Ex Vivo Assessments of Human Nodular Calcification: Optical Frequency Domain Imaging and Histopathology
Circulation, Volume 146, Issue Suppl_1, Page A12487-A12487, November 8, 2022. Introduction:It has been reported that a nodular calcification is associated with a calcified nodule and the reappearance of in-stent failure after percutaneous coronary intervention.Hypothesis:This study evaluated characteristics of nodular calcification on optical frequency domain imaging (OFDI) image in comparison to histopathology.Methods:One hundred and seven matched OFDI and histopathological cross-sections from 13 coronary arteries of 5 human autopsy hearts were evaluated. In histopathological assessment, a nodular calcification was defined as a fragmented calcification with accumulated fibrin. In OFDI analysis, calcification arc, shape of luminal surface, lumen side shape of calcification, irregularity of lumen surface, and irregularity of calcification surface of lumen side were analyzed in each OFDI image.Results:There were 10 nodular calcifications and 97 non-nodular calcifications in histopathological slices. The calcification arc was significantly smaller in nodular calcification than in non-nodular calcification [89.5° (56.4-108) vs. 126° (82.0-190), p =0.02]. OFDI features of a nodular calcification were characterized by a convex shape of the luminal surface (90.0% in nodular calcifications vs. 6.2% in non-nodular calcifications, p
Abstract 10851: A Randomized Study to Compare LDL-C-Lowering Effects of Inclisiran With Usual Care vs Usual Care Alone in Patients With Recent Hospitalization for an Acute Coronary Syndrome: Rationale and Design of the VICTORION-INCEPTION Trial
Circulation, Volume 146, Issue Suppl_1, Page A10851-A10851, November 8, 2022. Introduction:Patients are at high risk for a recurrent cardiovascular (CV) event in the first year following acute coronary syndrome (ACS). Low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for recurrent CV events. Despite the availability of lipid-lowering therapies (LLT), many patients fail to achieve guideline recommended LDL-C
Abstract 12634: A Novel in-vitro Patient-Specific Re-Engineered Cardiomyocyte Model of Multifocal Ectopic Purkinje-Related Premature Contractions
Circulation, Volume 146, Issue Suppl_1, Page A12634-A12634, November 8, 2022. Introduction:Multifocal ectopic Purkinje-related premature contractions (MEPPC), the most recent addition to the spectrum ofSCN5A-mediated cardiac channelopathies, is characterized by frequent premature ventricular complexes (PVCs) originating from the Purkinje system, atrial arrhythmias, and a predilection for PVC-mediated dilated cardiomyopathy.Hypothesis:To investigate the electrophysiology phenotype of MEPPC in a novel, patient-specific, re-engineered cardiomyocyte model.Methods:Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated from a 27-year-old male with a history of frequent, multifocal PVCs and atrial tachycardia, positive for a putative MEPPC-causativeSCN5Avariant (p.Q419P). A CRISPR-Cas9 Q419P variant-corrected isogenic control (IC) was created to establish the normalized electrophysiology recordings for that MEPPC model. The standard whole-cell patch clamp technique was used to measure Q419P-SCN5A- and IC-derived NaV1.5 sodium currents using voltage clamp configuration. In addition, action potential duration (APD) of the iPSC-CMs were measured using FluoVolt optical voltage-sensing dye.Results:Analysis of the current-voltage relationship revealed that neither peak sodium current densities nor late inward sodium current were impacted by Q419P-SCN5A. However, Q419P-SCN5A significantly right-shifted the V1/2in inactivation by 8.3 mV from -81.1±1.7 mV (IC, n=5) to -72.8±0.2 mV (Q419P-SCN5A, n=6, p
Abstract 13583: Conduction System Pacing Experience: His Bundle vs. Left Bundle Branch Area Pacing at Columbia University
Circulation, Volume 146, Issue Suppl_1, Page A13583-A13583, November 8, 2022. Introduction:Conduction system pacing (CSP) with His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) are utilized as alternatives to RV endocardial and biventricular pacing. Which patients gain the most benefit from CSP remains an area of active investigation.Objective:To report on the early experience with HBP and LBBAP conduction system pacing at an academic medical center.Methods:All patients with a Medtronic 3830 SelectSecure lead implanted from 3/2016 to 5/2022 at Columbia University were selected for chart review. Patients were excluded if follow up interrogation or clinical data were unavailable for review.Results:A total of 36 patients were included and 3 were excluded for lack of follow up. 25 patients had HBP and 11 patients had LBBAP (Table 1). Average time from implant to most recent interrogation for HBP was 530.8 ± 506.2 days, range 22 – 1589, compared to 113.6 ± 149.6 days, range 10 – 397, for LBBAP. The implant threshold was significantly higher in HBP compared to LBBAP (1.58 ± 1.06 V vs. 0.57 ± 0.19 V, p=0.004) (Table 1). There were increased threshold in both groups at follow up compared to initial implant HBP (1.81 ± 1.19 V vs 1.58 ± 1.06, p=0.17) and LLBAP (< 30 days of follow up [n=4], 0.84 ± 0.66 V vs 0.58 ± 0.22 V,p=0.46; >30 days of follow up [n = 7], 1.34 ± 1.40 vs 0.57 ± 0.19, p=0.18) although it was not significant. Complication rates were low, one HBP lead was deactivated due to high threshold, two LBBAP patients required lead revision, one for dislodgement and one for pocket infection.Conclusions:CSP is a feasible and safe procedure. Higher thresholds were observed in the HBP group at implant compared to the LBBAP group. There was a trend of an increased threshold over time in both groups. Ongoing monitoring of the LBBAP is crucial for long term feasibility.