tbuckley/cabot-search huggingface dataset:
Abstract 15587: Iimpact of Body Mass Index on Bleeding Events Patients Undergoing Percutaneous Coronary Intervention With or Without High Bleeding Risk
Authors: Michael Gao, Alessandro Spirito, Samantha Sartori, Birgit Vogel, Karim Kamaleldin, Mashal Nathani, Kenneth F Smith, Samin K Sharma, Annapoorna Kini, George Dangas, Roxana Mehran
Journal: Circulation (2023)

Introduction: High body mass index (BMI) values are associated with a lower risk of ischemic complications after percutaneous coronary intervention (PCI). Hypothesis : Higher BMI values may correlate with fewer bleeding after PCI in patients meeting or not the High Bleeding Risk (HBR) criteria of the Academic Research Consortium (ARC). Methods: All patients undergoing PCI between 2012 and 2019 at the Mount Sinai Hospital were included and stratified in 5 BMI categories according to World Health Organization definition. Patients where considered at HBR if they fulfilled ≥1 major or ≥2 minor ARC-HBR criteria. The primary outcome was major bleeding, the secondary outcome was post-discharge major bleeding at 1 year after PCI. Risks for these outcomes were obtained using a multivariable Cox regression model adjusted for the ARC-HBR criteria. Results: Among 16,229 patients, 20.2% had a BMI ≥18.5-25 (normal), 40.7% had a BMI ≥25-30, 24.4% had a BMI ≥30-35, 9.2% had a BMI ≥35-40, and 4.8% had a BMI ≥40 kg/m 2 . The proportion of patients meeting the ARC-HBR criteria progressively decreased from 48% in the normal BMI group to 41% in the highest BMI group. As compared to the normal BMI group (6.0%), the 1-year risk of major bleeding was significantly lower (p&lt;0.05) in the groups with BMI ≥25-30 (4.1%, adj. HR 0.73, 95% CI 0.60-0.88), with BMI ≥30-35 (3.5%, Adj. HR 0.62, 95% CI 0.49-0.77), with BMI ≥35-40 (4.2%; Adj. HR 0.72, 95% CI 0.54-0.9), while it was similar in the group of BMI ≥40 (4.9%, Adj. HR 0.83, 95% CI 0.58-1.18) ( A ). These differences were driven by lower rates of in-hospital bleeding in patients with BMI ≥25-40 kg/m 2 . Among HBR patients, 1-year rates of major bleeding were consistently above 4% in each BMI category, but relatively lower for BMI ≥25-40 kg/m 2 ( B ). Conclusions: BMI values between 25 and 40 kg/m 2 were associated with an attenuated risk of major bleeding at 1-year in patients undergoing PCI and this association was consistent among HBR individuals.
Abstract 13098: Worsening Tricuspid Regurgitation Associated With Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation: A Systematic Review and Meta-Analysis of Over 66,000 Patients
Authors: Saed Alnaimat, Mark Doyle, Kousik Krishnan, Robert W Biederman
Journal: Circulation (2023)

Introduction: Worsening TR following either PPM or ICD implantation is an emerging clinical challenge. Early recognition of this entity is essential in guiding treatment. Hypothesis: Despite many technological advances in electrophysiology, transvenous lead placement currently remains an integral part of cardiac device implantation procedures. While worsening of TR post-device does not seem to be surprising, it is counter-intuitive and eventually leads to right-sided heart failure symptoms. Methods: We searched electronic databases from inception to January 2023 for published studies that reported incidence of TR worsening post-device implantation. Log odds ratio was used to summarize group differences. Results: Our analysis included 29 studies with 66,590 participants. Patients with device implantation (n=1,008) were significantly more likely to develop worsening TR as compared to controls (n=58,605) (OR: 3.18, p&lt;0.01). Amongst a total of 7,777 patients, pooled incidence of at least one-degree worsening of TR post-implantation was 23%. Worsening TR significantly increases mortality (HR 1.42, p=0.02). Larger right atrial area (OR 1.11, p&lt;0.01) is significantly associated with an increased risk of worsening TR, while males are less likely to develop this complication as compared to females (OR 0.74, p&lt;0.01). Importantly, there is no statistically significant difference between the type of implanted device (ICD vs PPM) and post-device TR. Further, RV dysfunction, pulmonary artery pressure, baseline mitral regurgitation, LVEF, baseline atrial fibrillation, and age have no association with worsening TR. Conclusions: A substantial number of patients undergoing PPM or ICD implantation are at an increased risk of worsening TR. Importantly, in this largest review to date incorporating over 66,000 patients, this significantly increases mortality by greater than 140%, accordingly deserving more recognition and clinical attention in the current era.
Abstract 15581: Increasing Myocardial Carnosine Levels Reduces Adverse Remodeling During Heart Failure
Authors: Benjamin Doelling, David Hoetker, Kenneth Brittian, Robert E Brainard, Aruni Bhatnagar, Shahid P Baba
Journal: Circulation (2023)

Background : Lipid peroxidation products, such as acrolein, are highly toxic aldehydes generated during pathological remodeling and associated with heart failure. Until now, no translatable therapy has been tested to remove these toxic products from heart and examine the subsequent effects on failing hearts. The heart contains small histidyl dipeptides, such as carnosine (β-alanine-histidine), which bind lipid peroxidation products. Carnosine is decreased in failing hearts and its levels can be increased by supplementing the precursor, β-alanine. This study investigates the cardioprotective and translational potential of β-alanine supplementation in a transaortic constriction (TAC) model of heart failure. Hypothesis : Increasing myocardial carnosine via β-alanine supplementation will improve cardiac function during heart failure. Approach : Male wild-type C57BL/6J mice were treated either (a) water alone, (b) β-alanine 1 week prior to TAC, or (c) β-alanine (20g/L) in water 4 weeks post TAC. Supplementation of β-alanine was continued for 8 weeks, followed by serial echocardiography, biochemical, and mass spectrometry analysis. Results : Myocardial carnosine increased ~3-4-fold after 1 week of β-alanine feeding compared with water alone (p &lt; 0.05). β-alanine pre-feeding compared with water alone, after 8 weeks of TAC, decreased left ventricular (LV) mass (β-alanine: 174 ± 29 vs water: 241 ± 17 mg, p &lt; 0.05) and LV inner diameter at systole (β-alanine: 2.2 ± 0.6 vs water: 3.5 ± 0.4 mm, p &lt; 0.05) and diastole (β-alanine: 3.5 ± 0.4 vs water: 4.4 ± 0.3 mm, p &lt; 0.05), and increased ejection fraction (β-alanine: 67 ± 14% vs water: 42 ± 9%, p &lt; 0.05) and cardiac output (β-alanine:13.6 ± 2.6 vs water: 10.7 ± 1.0 mL/min, p &lt; 0.05). Post-TAC β-alanine intervention decreased LV mass (β-alanine :177 ± 8 vs water: 214 ± 11 mg, p &lt; 0.05), hypertrophic markers Nppa and Myh7 , and increasingly removed acrolein from heart by conjugation (β-alanine: carnosine-propanal: 12.2 ± 0.4 vs water: 0.7 ± 0.4 pmoles/mg protein, p &lt; 0.0001). Conclusion : Increasing myocardial carnosine via oral supplementation alleviates pathological remodeling, possibly through quenching reactive aldehydes. These findings lay foundation to test the feasibility of β-alanine in heart failure patients.
Abstract 13106: Two-Year Clinical Outcomes of Staged Transcatheter Mitral Edge-to-Edge Repair After Transcatheter Aortic Valve Replacement
Authors: Takashi Nagasaka, Mamoo Nakamura
Journal: Circulation (2023)

Introduction: Residual significant MR has been linked to an increased risk of adverse clinical events in patients undergoing TAVR. However, the effectiveness of staged TEER after TAVR has been poorly assessed. Hypothesis: To investigate clinical outcomes of staged transcatheter edge-to-edge repair (TEER) for residual significant mitral regurgitation (MR) after transcatheter aortic valve replacement (TAVR). Methods: This observational study included consecutive patients with residual grade 3+ or 4+ MR after TAVR performed at our institution between April 2016 and November 2020. The primary composite outcomes were all-cause mortality and heart failure (HF) hospitalization at 2 years, with HF hospitalization assessed as a secondary outcome for all-cause mortality. Additional analyses, including changes in MR grade and New York Heart Association (NYHA) functional classification, were performed. Results: Among 314 patients, 104 (33.1%) treated with staged TEER and 210 (66.9%) treated with medical therapy alone were enrolled. Patients who underwent staged TEER had a lower rate of primary composite outcomes than those who received medical therapy alone (33.7% vs. 48.1%, p=0.027) (Figure1). However, there was no significant difference in all-cause mortality (11.5% vs. 13.8%, p=0.46) or HF hospitalization (31.7% vs. 42.9%, p=0.061). Staged TEER was associated with a marked improvement in the MR grade and NYHA class from baseline to 2 years. Conclusions: Staged TEER following TAVR was associated with improved clinical outcomes and a reduced MR grade. The findings suggest that TEER should be considered a potential treatment option for significant residual MR in patients who have previously undergone TAVR.
Abstract 14198: Therapy for Myocardial Ischemia-Reperfusion Injury Using Novel Allogenic Mitochondria and Associated Organelle Complex
Authors: Yuuki Shimizu, Takumi Hayashi, Yiyang Che, Zhongyue Pu, Hisashi Ota, Rick Tsai, Masashi Suganuma, Toyoaki Murohara
Journal: Circulation (2023)

Background: Ischemia and reperfusion (I/R) injury induces intracellular calcium overload and generation of reactive oxygen species, which trigger intracellular mitochondrial damage, resulting in cardiomyocyte apoptosis. Freshly prepared autologous mitochondria improved damaged cardiac function, however, little is known whether allogenic mitochondrial organelle complex -Q (MRC-Q) can be replenished in the heart to achieve cardioprotective effects against I/R injury. Purpose: The aim of this study was to investigate whether the exogenous administration of allergenically isolated mitochondria leads to a protective effect on the myocardium after I/R injury using a well-established murine model. Methods and Results: The MRC-Q used in the current experiments were isolated by a proprietary technology ( WO2021132735A2) . All MRC-Q was frozen and stored at -80 °C before use. First, purified GFP-labeled HUVEC-derived MRC-Q were added to a rat cardiomyocyte cell line, and observed to be uptaken in cardiomyocytes in a time-dependent manner, which was also confirmed by quantitative polymerase chain reaction detecting human mitochondria DNA in rat cardiomyocytes. In addition, we demonstrated that cell viability was improved in the MRC-Q-treated group 96 hours after hypoxia/reoxygenation (H/R). Further examinations suggested the one of mechanism on cardioprotection by incorporating MRC-Q into the cardiomyocyte to be mediated by the secretion of mitochondria-derived peptides (MDP), which could inhibit apoptosis-promoting signals in addition to anti-ROS activity of MRC-Q. Next, we examined potential cardioprotective effect of MRC-Q administration on I/R injury in a murine model. Simultaneously at reperfusion, MRC-Q were administered intramyocardially in the damaged myocardium area. Compared to the vehicle group, MRC-Q-treated group showed a reduction in infarct size with fewer apoptotic cells, a decrease in circulating cardiac enzymes, and an improvement in cardiac function 24 hours after reperfusion. Finally, a preclinical pig model also confirmed the cardioprotective effects of MRC-Q. Conclusion: Our data demonstrated that MRC-Q have a protective effect on the heart by modulating cardiac apoptosis after ischemia/reperfusion injury.
Abstract 14054: Pre-Hospital Predictors of Cardiogenic Shock Among ST-Segment Elevation Myocardial Infarction Patients With and Without Cardiac Arrest: Implications for Shock Teams
Authors: Cathevine Yang, Terry Lee, Andrew Kochan, Madeleine Barker, Thomas Roston, Joel Singer, Brian Grunau, Jennifer Helmer, Graham C Wong, Christopher Fordyce
Journal: Circulation (2023)

Introduction: Cardiogenic shock (CS) develops in up to 8.6% of patients with STEMI and is associated with poor outcomes. Early identification of patients at risk of CS is paramount to enable timely mobilization of shock teams to improve outcomes. Hypothesis: We hypothesized that pre-hospital clinical parameters can predict development of CS in STEMI patients undergoing primary PCI. Using these predictors, we developed a risk score to rapidly identify patients at risk of developing CS. Methods: We performed a retrospective cohort study using prospective data from a centralized STEMI registry of a healthcare system serving 1.25 million people. Patients presenting with STEMI with intent to receive primary PCI between 2012 to 2020 were included. Logistic regression was used to assess the relationship between predictors and the occurrence of CS at any point from first medical contact to hospital discharge. The prediction model was converted to a risk score by scaling of the regression coefficients. The accuracy of the risk score was determined using C-statistic. Results: Among 2736 consecutive STEMI patients, 15.2% (n=415) developed CS. Overall, 10.9% of patients had prehospital cardiac arrest, which was more likely in those with CS (46.5% vs. 4.5%, p&lt;0.001). Patients with CS were more likely to have prolonged first medical contact-to-device time per national guidelines (74.7% vs. 53.3%, p&lt;0.001). Regression analysis identified 8 parameters that predict CS as shown in Table 1. Two models, with and without cardiac arrest, were developed. Both models show C-statistics of 0.80 and above. Conclusions: Among STEMI patients with intent to undergo primary PCI, we identified 8 clinical parameters that strongly predict CS. This has been developed into a scoring system which can be easily used by emergency service providers to rapidly identify patients with CS and enable timely shock team activation.
Abstract 12945: Six-Month Adherence Among Early Inclisiran Initiators vs. Anti-PCSK9 mAbs Users: A Retrospective Analysis of US Claims Databases
Authors: Charlene Niu, Akhil Parlapalli, Joseph Neenan, Xinshuo Ma, Abena Osei-Wusu, Jina Park, Sean McElligott
Journal: Circulation (2023)

Introduction: Poor adherence with statins is an obstacle in achieving LDL-C targets for patients with atherosclerotic cardiovascular disease (ASCVD). Inclisiran is a first-in-class, long-acting, small-interfering RNA approved as an adjunct to diet and maximally tolerated statin for adults with ASCVD or heterozygous familial hypercholesterolemia who require additional LDL-C lowering. It is initially administered subcutaneously by an HCP, again at 3 months and then twice yearly. Real-world studies assessing adherence of inclisiran are limited. Hypothesis: This study evaluated treatment adherence at 6 months for patients who newly initiated inclisiran, alirocumab (every 2 weeks or 1/month) or evolocumab (every 2 weeks or 1/month) since 2022. Methods: This retrospective, observational study utilized the US Komodo Health database from 1/1/21 - 2/8/23. Komodo Health is a nationally representative longitudinal database that captures 330 million patients in the US from open and closed administrative databases. Patients were aged ≥18 years, had 12 months of continuous enrollment (CE) before the index date, 6 months CE after the index date and a first claim for inclisiran, alirocumab, or evolocumab in the identification period (1/1/22 - 10/31/22). Adherence was defined as the proportion of days covered (PDC): the number of days covered by the drug divided by the observational period (6 months after index date). Poor adherence was defined as PDC &lt;80%. Results: A total of 981 patients had ≥6 months of CE after the index date and were in the inclisiran cohort;11,330 patients were in the alirocumab cohort and 30,515 in the evolocumab cohort. Mean (SD) 6-month adherence was highest for inclisiran at 0.85 (0.22) followed by 0.72 (0.30) for alirocumab and 0.70 (0.30) for evolocumab. The proportion of patients with high adherence (PDC ≥0.8) was 69.9% for inclisiran, followed by 51.0% for alirocumab and 48.6% for evolocumab. Of patients in the inclisiran cohort (n=981), 70.9% received a second dose with a mean time of 90.9 (32.0) days between doses. Conclusions: Early evidence post launch shows patients initiating inclisiran had higher adherence vs anti-PCSK9 mAbs. Inclisiran is a new option for patients with ASCVD who may have difficulty reaching their LDL-C target.
Abstract 12946: Among Patients With Acute Coronary Syndromes, is the Risk of Hyperglycemia for In-Hospital Mortality Similar in Men and Women?
Authors: Jose C Nicolau, Santiago A Castro Vintimilla, Renato Rosa, Adriadne J Bertolin, Maria C Andrade, Leonardo V Salis, Jorge L Montero Ribera, Nadia R Quintanilha, Glaylton S Santos, Luciano M Baracioli, Roberto R Giraldez, Felipe G Lima, Cesar C Pereira, Andre M Nicolau, Remo H Furtado, Robert P Giugliano
Journal: Circulation (2023)

Introduction: Hyperglycemia is associated with higher in-hospital mortality in acute coronary syndromes (ACS) patients (pts). However, interaction between hyperglycemia, mortality and sex in ACS pts is poorly understood. Hypothesis: To analyze the relationship between hyperglycemia and in-hospital mortality stratified by sex. Methods: We analyzed 4633 ACS pts included in an administrative databank. Categorical variables were compared using the chi-square or Fisher exact tests as appropriate; continuous variables were compared by the Student’s t-test if Gaussian distribution, or Mann-Whitney test if not. Logistic regression test was used for the interaction analysis and adjusted models. ROC curves were developed and compared by the De Long test. The first glucose measurement obtained during hospitalization was utilized. Hyperglycemia was defined as glucose ≥126.5 mg/dL: best cut point, derived from the ROC curve for the whole population. Results: A) In comparison with men, women were older, with higher rates of hyperglycemia, hypertension and diabetes, and lower rates of prior MI, CABG, ST-elevation MI, and in-hospital PCI. B) As shown in figure there was a stronger association between hyperglycemia and in-hospital mortality in women (OR 3.34) than in men (OR 2.46 p-interaction &lt;0.001). C) ROC analysis of the predictive value of hyperglycemia for in-hospital mortality showed areas under the curve (AUC) of 0.64 (95% CI 0.60-0.67), 0.62 (95% CI 0.58-0.66) and 0.66 (95% CI 0.61-0.71) resp. for the whole population, men, and women (P&lt;0.01 for each), with no difference between men and women (P 0.23). D) Significant multivariate predictors of in-hospital mortality included: hyperglycemia, cardiogenic shock and age for both sexes; ST-elevation MI and in-hospital PCI only for men; and previous MI and in-hospital CABG only for women. Conclusions: In ACS pts, the association of hyperglycemia with higher in-hospital mortality is greater in women than in men.
Abstract 12950: A Nationwide Remote Patient Intervention Hypertension Program: Can Remote Patient Monitoring and a Multi-Disciplinary Team of Clinicians Improve Blood Pressure Control?
Authors: David I Feldman, Marcus L Campbell, Sarine Babikian, Randall Curnow, Theodore Feldman, Marat Fudim
Journal: Circulation (2023)

Introduction: Traditional methods for diagnosing and treating HTN, which is the most common modifiable risk factor accounting for ASCVD in the US, have been ineffective. Innovative solutions, like remote patient monitoring (RPM), can transform how we provide longitudinal care for patients with HTN. Hypothesis: An advanced practice provider led HTN program, which leverages RPM and technology-enabled treatment protocols, can provide a scalable solution for optimizing HTN management nationwide. Methods: Cadence is a healthcare technology organization that enrolled patients into a virtual HTN program in PCP clinics in 11 states across the US from February 2022 to April 2023. Eligible patients were Medicare enrollees who had a diagnosis of HTN based on ICD-10 codes, mean blood pressure (BP) &gt;140/90 (using last 3 EMR-based vitals) and were enrolled for at least 30 days. Using daily vitals from a cellular enabled BP cuff and scheduled visits, a team of multidisciplinary clinicians leveraged technology-enabled clinical protocols to facilitate optimization of HTN control. A two-sample t-test was used to detect a difference in mean BP. Results: A total of 4006 patients were enrolled (mean age 73 +/- 9, 70% White) with a baseline BP of 144/83 mmHg. The total reduction in systolic BP (SBP)/diastolic BP (DBP) was 9/6 (p&lt;0.001) in the last week compared to the first week (mean follow-up of 136 +/- 92 days). The total number of vitals recorded, clinical visits and phone calls completed, and high acuity clinical alerts resolved is depicted in Figure 1A. The SBP/DBP reductions by different BP strata are depicted in Figure 1B. There was a ~2x increase in the number patients at goal (BP&lt;130/80) in the last week compared to the first week (31% vs. 15%; p&lt;0.001). Conclusions: A remote patient monitoring HTN program not only can improve the diagnosis of hypertension, but also can significantly reduce blood pressure, and in doing so help more patients achieve guideline recommended BP goals.
Abstract 12927: Impact of AAV- <i>MYBPC3</i> Gene Transfer on Heart Structure and Function in Human and Mouse Models of Hypertrophic Cardiomyopathy
Authors: Catherine Vitelli, Lening Zhang, Ryan Murphy, Bartlomiej Blus, Terri Christianson, Alexander Giaramita, John Holtzinger, Britta Handyside, Hannah May, Ann Pham, Tu Nguyen, Huiyu Zhou, Ioanna Ntai, Giulia Mearini, Valeria Ricotti, Thomas Voit, Thomas Eschenhagen, Lucie Carrier, Pooja Agarwal, Stuart Bunting, Marius Sumandea
Journal: Circulation (2023)

Background: Hypertrophic cardiomyopathy (HCM) is a life-threatening inherited heart disease characterized by left ventricular hypertrophy and diastolic dysfunction. The most common cause of HCM is genetic variants in MYBPC3 , encoding cardiac myosin binding protein C (cMyBP-C), a sarcomeric protein with structural and regulatory roles. The majority of MYBPC3 gene variants are truncating leading to protein haploinsufficiency. Hypothesis: Transfer of a functional copy of MYBPC3 to heart muscle deficient in cMyBP-C will lead to sustained improvements in cardiac function. Aims: To determine whether BMN 293 (AAV-hMYBPC3) can restore cMyBP-C levels in the sarcomere and halt and/or reverse disease progression in non-clinical models of genetic HCM due to MYPBC3 deficiency. Methods: BMN 293 is an adeno-associated virus (AAV) vector that encodes wild-type human MYBPC3 under the control of a cardiomyocyte-selective promoter. We transduced human iPSC-derived cardiomyocytes and engineered heart tissues (EHTs) carrying a compound heterozygous truncating MYBPC3 mutation (MYBPC3 -/- ) with BMN 293 and assessed cMyBP-C levels and contractile parameters. We also systemically administered BMN 293 to MYBPC3 -/- mice and assessed cardiac distribution of human cMyBP-C by molecular and histological methods and determined its impact on left ventricular hypertrophy and function by echocardiography and other imaging techniques. Results: BMN 293 transduction of human iPSC MYBPC3 -/- cardiomyocytes and EHTs resulted in high levels of human MYBPC3 mRNA and cMyBP-C protein, correct incorporation of cMyBP-C into the sarcomere, and complete normalization of contractile kinetics. BMN 293 was well tolerated in MYBPC3 -/- mice and resulted in uniform restoration of cMyBP-C expression throughout the heart and significant correction of structural and functional cardiac abnormalities. Conclusions: A single IV infusion of BMN 293 to MYBPC3 -/- mice resulted in early and sustained reduction in left ventricular hypertrophy and durable improvements in diastolic function.