tbuckley/cabot-search huggingface dataset:
Abstract Sa1002: Vasopressor or Advanced Airway First in Cardiac Arrest?
Authors: Henry Wang, Mohamud Daya, Robert Schmicker, Michelle Nassal, Masashi Okubo, ELISABETE ARAMENDI, Erik Alonso, Ahamed Idris, Ashish Panchal, Xabier Jaureguibeitia, Jestin Carlson, Graham Nichol
Journal: Circulation (2024)

Background: While early vasopressor administration (epinephrine, vasopressin) and early advanced airway management (laryngeal tube [LT], endotracheal intubation [ETI]) have been associated with improved outcomes after out-of-hospital cardiac arrest (OHCA), their optimal sequence during resuscitation remains unclear. Aims: To determine the associations between vasopressor-airway resuscitation sequence and OHCA outcomes and quality of cardiopulmonary resuscitation (CPR) in the Pragmatic Airway Resuscitation Trial (PART). Methods: Secondary analysis of the PART trial, which compared initial airway strategies of LT vs. ETI in adults with OHCA. For each patient we determined times of advanced life support (ALS) rescuer arrival, first vasopressor administration, and first successful airway insertion. We defined resuscitation sequence as: 1) vasopressor-first or 2) airway-first. We excluded cases with either vasopressor or airway given before ALS arrival and those that received neither. We used Generalized Estimating Equations to determine associations between resuscitation sequence and outcomes (72-hour survival, ROSC, survival to hospital discharge, survival with favorable neurologic status) and CPR quality (chest compression rate 100-120 per min, chest compression fraction (CCF) ≥0.8, ventilation rate 8-12 per min), adjusting for known confounders. Secondary analyses stratified by initial rhythm (shockable vs. non-shockable) and time to first intervention (vasopressor or airway, ≤10 vs. &gt;10 mins). Results: Of 3,004 patients in the parent trial, we included 2,404, including 1,821 vasopressor-first and 583 airway-first. Median intervention times were: ALS arrival-to-vasopressor 8 mins (IQR 6-11) and ALS arrival-to-airway 11 mins (8-15). Compared with airway-first, vasopressor-first sequence was not associated with 72-hour survival (aOR 0.89; 95% CI: 0.66-1.20), ROSC (0.79; 0.62-1.001), hospital survival (0.98; 0.63-1.53), or hospital survival with favorable neurologic status (0.84; 0.47-1.51). Associations were similar when stratified by initial rhythm or time to first intervention. In those with available chest compression (n=1,699) and ventilation (n=892) data, vasopressor-first sequence was not associated with chest compression rate (aOR 0.90; 95% CI: 0.73-1.11), CCF ≥0.8 (0.94; 0.72-1.21) or ventilation rate 8-12 per min (0.79; 0.57-1.08). Conclusions: Vasopressor-airway resuscitation sequence is not associated with OHCA outcomes or CPR quality.
Abstract 4146863: Efficacy of Hydralazine-Isosorbide-Dinitrate and Sodium-glucose Cotransporter-2 Inhibitors in Reducing Short-Term Readmission in African Americans with Advanced Heart Failure
Authors: Mark Kluever, Masi Javeed
Journal: Circulation (2024)

Introduction: The treatment of heart failure (HF) with hydralazine-isosorbide dinitrate (H-ISDN) in African Americans (AA) with New York Heart Association (NYHA) III-IV who remain symptomatic despite optimal medical therapy is a class Ia indication. However, the efficacy of guideline directed medical therapy (GDMT) which combines sodium-glucose cotransporter-2 inhibitors (SGLT2i) and H-ISDN in reducing hospital readmissions has not been well studied. Hypothesis: In self-identified AA adults with advanced heart failure on GDMT including hydralazine-isosorbide dinitrate, the use of a SGLT2i reduces hospitalization for HF. Methods: The patients studied were self-identified AA with advanced HF on GDMT [including any dose of an angiotensin receptor-neprilysin inhibitor (ARNi) or an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), a mineralocorticoid receptor antagonist (MRA), a beta-blocker (BB), H-ISDN, with or without treatment with an SGLT2i]. Data was obtained from the Hospital Corporation of America (HCA) enterprise-wide database from January 2020 to September 2023 using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). The final cohort was divided into two groups: Group 1 consisted of those treated with an ARNi/ACEi/ARB, MRA, a beta blocker, and H-ISDN while Group 2 included those receiving the same combination of medications with the addition of an SGLT2i. Differences in baseline characteristics were analyzed between the two groups. Logistic regression was used to analyze the relationship between the treatment groups and hospital readmission within 90 days. Results: Only 517 AA met inclusion criteria and did not meet exclusion criteria, which included a history of valvular heart disease, hypertrophic or restrictive cardiomyopathy, active myocarditis, history of cardiac arrest, and life-threatening arrhythmias. When controlling for age, gender, diabetes, chronic kidney disease, atrial fibrillation, body mass index, and smoking status, there was no significant difference in the likelihood of 90-day hospital readmission between patients whose GDMT with H-ISDN included an SGLT2i and those whose treatment did not. Conclusions: The results suggest the incorporation of an SGLT2i into GDMT with H-ISDN in AA with advanced HF does not confer additional benefits in the reduction of short-term hospital readmissions for heart failure.
Abstract Or106: Automated cardiac arrest detection incorporated in a wristband: First experience with spontaneous cardiac arrest detection
Authors: Roos Edgar, Niels Scholte, Kambiz Ebrahimkheil, Marc Brouwer, Rypko Beukema, Masih Mafi-Rad, Kevin Vernooy, Sing Yap, Eelko Ronner, Nicolas Van Mieghem, Eric Boersma, Aysun Cetinyurek-Yavuz, Peter Stas, Niels Royen, Judith Bonnes
Journal: Circulation (2024)

Introduction: Survival from out-of-hospital cardiac arrest depends on immediate recognition and early cardiopulmonary resuscitation. Especially for unwitnessed cardiac arrest, survival chances are poor due to delays in receiving help. Automated cardiac arrest detection using wearables could facilitate early help. In the DETECT-1 study, an algorithm for circulatory arrest detection was developed using wrist-derived photoplethysmography (PPG) from patients with induced circulatory arrest, yielding 98% sensitivity. Next step is the validation of this algorithm in spontaneous cardiac arrest events. Goal: This study presents the first experience with the PPG algorithm for cardiac arrest detection in hospitalized patients with spontaneous cardiac arrest. Methods: The study population consisted of patients who underwent transcatheter aortic valve implantation (TAVI) complicated by an episode of cardiac arrest, and patients admitted to the intensive care unit (ICU) in whom life sustaining treatment was withdrawn, while wearing the PPG wristband. Continuous ECG, arterial blood pressure data, and/or procedural logs were used as reference standard. The developed PPG algorithm for cardiac arrest detection was used to study sensitivity for cardiac arrest detection. Additionally, the mean arterial pressure (MAP) and pulse pressure, determined from the arterial blood pressure at the time of the algorithm’s cardiac arrest alarm, were analyzed. Results: A cardiac arrest occurred in 15 patients (9 TAVI patients and 6 ICU patients), of whom 2 had ventricular fibrillation, 11 pulseless electrical activity (Figure 1), and 2 asystole. Cardiac arrest was successfully detected in 14 out of the 15 patients, yielding a sensitivity of 93% (95% CI 66-100%). The false negative alarm was related to noisy PPG signal resulting from the immediate resuscitative interventions of the medical team. PPG data were identified as cardiac arrest at a median MAP of 37 mmHg (IQR 26-55 mmHg) and a median pulse pressure of 16 mmHg (IQR 6-18 mmHg). There were no false positive cardiac arrest alarms. Conclusion: The PPG algorithm successfully detected all but one cardiac arrests, which holds promise for future implementation of wristband-based cardiac arrest detection. Moreover, there were no false positive alarms. As a the next step, the PPG algorithm needs to be validated in a larger sample of cardiac arrest events and potential false positive alarms need to be studied thoroughly during daily life use.
Abstract 4147145: Short Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy versus 1-Year Dual Antiplatelet Therapy after Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials
Authors: Meghna Joseph, Mrinal Murali Krishna, Chidubem Ezenna, Vinicius Pereira, Ancy Jenil Franco, Andrew Goldsweig
Journal: Circulation (2024)

Introduction: Current guidelines recommend dual antiplatelet therapy (DAPT) for 6 months for stable ischemic heart disease and 12 months for acute coronary syndrome following percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation. However, long-term DAPT is associated with increased bleeding risk. Objective: To compare short DAPT (≤3 months) followed by P2Y12 inhibitor (P2Y12i) monotherapy until 12 months vs. standard DAPT for 12 months in patients undergoing PCI with DES. Methods: We systematically searched PubMed, Scopus, and Cochrane Central databases for studies comparing short DAPT followed by P2Y12i monotherapy vs. 12-month DAPT following PCI. The co-primary outcomes were composite major adverse cardiovascular/cerebrovascular events (MACCE) and net adverse clinical events (NACE; MACCE + bleeding events) at 12 months post-PCI. Secondary outcomes were major and any bleeding, myocardial infarction (MI), stroke, stent thrombosis, all-cause and cardiovascular mortality, and target vessel revascularization (TVR) at 12 months post-PCI. Results: The systematic review identified 8 randomized controlled trials including 39,782 patients (short DAPT n=19,877, 49.96%). MACCE (RR 0.88; 95%CI 0.78-0.98; p=0.023; I 2 =0%) and NACE (RR 0.75; 95%CI 0.65-0.86; p&lt;0.001; I 2 =56%) at 12 months were significantly lower with short DAPT than 12-month DAPT. Major (RR 0.52; 95%CI 0.37-0.72; p&lt;0.001; I 2 =63%) and any bleeding (RR 0.55; 95%CI 0.42-0.73; p&lt;0.001; I 2 =80%) were also significantly lower with short DAPT. MI, stroke, stent thrombosis, all-cause and cardiovascular mortality, and TVR at 12 months did not differ significantly between short and 12-month DAPT. Conclusion: Short DAPT for ≤3 months followed by P2Y12i monotherapy after PCI with DES was associated with decreased MACCE, NACE, and bleeding without differences in other outcomes. Short DAPT should be considered for high-bleeding risk patients.
Abstract 4146709: TMEM65 regulates NCLX-dependent mitochondrial calcium efflux to limit pathogenic mitochondrial calcium overload
Authors: Joanne Garbincius, Oniel Salik, Henry Cohen, Carmen Choya-Foces, Adam Mangold, Angelina Makhoul, Anna Schmidt, Dima Khalil, Joshua Doolittle, Anya Wilkinson, Emma Murray, Michael Lazaropoulos, Alycia Hildebrand, Dhanendra Tomar, John Elrod
Journal: Circulation (2024)

Introduction: Mitochondrial calcium ( m Ca 2+ ) exchange regulates energy metabolism, but if perturbed causes m Ca 2+ depletion and energy starvation or m Ca 2+ overload and cell death. The mitochondrial sodium (Na + )-calcium exchanger, NCLX, is critical for m Ca 2+ efflux in the heart, and animal models support NCLX as a therapeutic target to limit pathogenic m Ca 2+ overload. However, the mechanisms that regulate NCLX activity are largely unknown, representing a key barrier to translation. Goal: We used proximity biotinylation screening to identify the NCLX interactome and define novel regulators of NCLX function. Hypothesis: Our screen identified the mitochondrial inner membrane protein, TMEM65, as an NCLX-proximal protein that potently enhances Na + -dependent m Ca 2+ efflux. Therefore, we hypothesized that TMEM65 promotes m Ca 2+ efflux through NCLX. Approach: We measured m Ca 2+ exchange in AC16 cardiomyocytes with TMEM65 overexpression (OE) or CRISPR/Cas9 genetic disruption of TMEM65 to test its effect on m Ca 2+ efflux, and used pharmacologic inhibition and genetic knockout to determine TMEM65’s functional dependence on NCLX. We evaluated TMEM65’s impact on murine cardiac function in vivo using an AAV9-shRNA knockdown strategy. Results: Deletion of TMEM65 attenuated Na + -dependent m Ca 2+ efflux, while inhibition or deletion of NCLX ablated the increase in m Ca 2+ efflux observed with TMEM65 OE. Proximity ligation assay revealed co-localization of TMEM65 and NCLX in intact cells. In silico molecular modeling and co-fractionation of NCLX and TMEM65 via size-exclusion chromatography support their existence in a common macromolecular complex. Mutagenesis studies identified residues N163/D167 as critical to TMEM65 function, suggesting their importance to its cooperation with NCLX. TMEM65 expression decreased in human and murine heart failure, and Tmem65 KD in mice promoted myocardial m Ca 2+ overload and impaired cardiac function. Notably, TMEM65 OE mitigated necrotic cell death during cellular Ca 2+ -overload in vitro . Conclusions: Loss of TMEM65 function disrupts NCLX-dependent m Ca 2+ efflux, causing pathogenic m Ca 2+ overload, cell death and organ-level dysfunction, whereas gain of TMEM65 function can attenuate these effects. Our findings demonstrate the essential role of TMEM65 in maintaining m Ca 2+ efflux and suggest modulation of TMEM65 as a novel therapeutic strategy to control m Ca 2+ homeostasis in heart failure and other pathologies featuring dysregulated m Ca 2+ exchange.
Abstract 4147215: Cardiac Magnetic Resonance Imaging vs Positron Emission Tomography in the Assessment of Viability in Ischemic Cardiomyopathy. The Alternative Imaging Modalities in Heart Failure (AIM-HF) Clinical Trial
Authors: Anahita Tavoosi, David Paterson, Eileen Omeara, James White, Eric Larose, Juhani Knuuti, Christiane Wiefels, Benjamin Chow, Li Chen, Linda Garrard, Riina Kandolin, Ann Guo, Robert deKemp, George Wells, Rob Beanlands, Lisa Mielniczuk
Journal: Circulation (2024)

Background: Patients with ischemic heart failure (IHF) often undergo myocardial viability assessment to help determine the appropriate treatment strategy, whether revascularization or medical therapy. However, there is a lack of evidence regarding the optimal imaging modality for this purpose. The present study aimed to compare the clinical outcomes of IHF patients undergoing cardiac magnetic resonance (CMR) versus positron emission tomography (PET) for myocardial viability assessment. Methods: We enrolled patients &gt;18 years with IHF and ejection fraction (EF) &lt; 45% needing viability assessment. Exclusions included those with cardiac devices, significant medical conditions, recent ST segment myocardial infarction (&lt;4 weeks), unsuitability for revascularization, or needing emergency revascularization/valve surgery. Patients were randomized to PET or CMR for viability detection. The primary endpoint was the composite of cardiac death, myocardial infarction, cardiac arrest, or cardiac re-hospitalization. Secondary endpoints evaluated the effect of imaging strategies on each composite component, including cardiac death. Results: Total of 116 patients were randomized to either the CMR group (n=60) or the PET group (n=56) at sites where both modalities were available. There were no significant differences between the CMR and PET groups in terms of average age (63.7±9.6 vs. 63.9±10.2), prevalence of male patients (90% vs. 89%), or NYHA class III or IV (40% vs. 38%). The mean EF was 25.5±7.9 in the CMR and 26.6±8.3 in the PET group, with a standardized difference of 0.264.Over a median (IQR) of 25.0 (15.3,29.6) months, the cumulative incidence rate (CIR) for the primary endpoint was 25.0% for CMR and 32.6% for PET (HR 0.74,CI 0.37-1.49,p=0.402).The CIR for cardiac death was 13.9% for CMR vs. 13.2% for PET (HR 1.12 (0.41,3.06,p=0.822)).(Fig.1) Conclusion: The result of this randomized cohort showed that among IHF patients who required a definition of viability, there were no significant differences in the incidence of important cardiac endpoints when either CMR or PET were used. Larger randomized clinical trials should be considered to confirm the current results.
Abstract 4146986: Removal of the Entrapped distal embolic protection system behind the stent frame during the percutaneous intervention of critically stenosed Saphenous venous graft. A Case Report.
Authors: Salman Abdul Basit, Nadia Jamil, Muhammad Sabih Saleem, Muhammad Hassan Shakir, Sunny Kumar, NISHANT SETHI
Journal: Circulation (2024)

Case Description and Procedural Technique: 86 year old female with a prior history of coronary artery bypass grafting presented with non-ST elevation MI underwent subtotal occlusion of vein graft supplying the large obtuse marginal artery. The left coronary bypass catheter was used to cannulate the vein graft, supplying the obtuse marginal artery. Balanced middleweight universal wire (BMW) was used to cross the lesion. Given the critical nature of the lesion, it was pre-dilated using a 2 mm balloon. Bare wire and emboshield NAV6 (2.5-4.8mm) embolic protection was then used for distal protection. Due to hemodynamically intolerance, direct stenting was opted for, and a 3.5 x 16 mm synergy stent was deployed over the BMW wire with accidental entrapment of the bare wire and embossed filter protection system behind the stent frame. We have then placed an un-inflated 2.5 mm balloon inside the stent frame over the BMW wire. A 1 mm sapphire balloon was advanced over the bare wire, and its distal tip was placed behind the proximal edge of the stent. It was then inflated at 8 atmospheres. Serial inflations behind the stent frame were done with slow advancement of the balloon, covering the entire length of the stent. The balloon was then upsized to 2 mm, and serial inflations were performed behind the stent frame. After creating enough lumen, the filter was pulled back and re-captured. The 2.5 mm balloon was then inflated inside the stent frame. The balloon was upsized to 3.5 mm for the good apposition of the stent frame. TIMI III flow was obtained without any complications. Discussion: Distal embolic protection with intravascular filters is often used during percutaneous intervention of saphenous venous grafts. Accidental entrapment of emboshield filter systems can occur behind the stent in emergent situations when buddy wire technique is used in the vein graft. Our technique describes removal of the entrapped filter in a safe manner keeping the stent frame in place without surgical intervention. A few similar cases have been reported in the literature with surgical removal of wire.
Abstract 4148059: Impact of Chronic Kidney Disease on Incidence of Atrial Fibrillation Following Heart Failure Exacerbation
Authors: Thomas Fretz, Sarah Fortna, Tanyanan Tanawuttiwat, Onyedika Ilonze, Mithilesh Das
Journal: Circulation (2024)

Introduction: Chronic kidney disease (CKD) is associated with increased morbidity and mortality in patients with heart failure (HF). Patients with HF have a high prevalence of CKD, affecting 50% or more of those with either preserved or reduced ejection fraction HF. Both heart failure and chronic kidney disease are associated with an increased incidence of atrial fibrillation (AF). However, the impact of chronic kidney disease on the incidence of AF in the heart failure population is incompletely understood. Hypothesis: Patients with a history of CKD have a higher risk of developing AF following HF hospitalization. Aims: Our goal with this study was to examine whether chronic kidney disease impacts the development of AF following HF hospitalization. Methods: This retrospective study included consecutive patients who were admitted to an academic tertiary care center over a 3 year time period with a primary diagnosis of heart failure exacerbation and no prior diagnosis of AF. The primary outcome was an incident of AF within 12 months after hospitalization. Demographic, comorbidity, echocardiographic data, and medications were obtained. Cox-regression analysis was performed to identify the predictors of new atrial fibrillation following heart failure hospitalization. Results: A total of 2,087 patients with CKD and 1,866 patients without CKD were identified and included in our study. Of those with a previous diagnosis of CKD, 22.7% developed AF at one year, whereas this occurred in 13.2% of those without previous diagnosis of CKD. This difference was statistically significant after controlling for age and comorbidities ( p&lt;0.001; RR 1.62; 95% CI 1.37-1.90) (Figure). Conclusion: A previous diagnosis of chronic kidney disease is a predictor of development of new atrial fibrillation at one year following heart failure hospitalization.
Abstract 4147041: Genetic evidence implicating collagen type VI a3 in heart failure risk and aortic health
Authors: Marie-Joe Dib, Joe David Azzo, Oday Salman, Hamed Tavolinejad, Cameron Beeche, Dipender Gill, Julio Chirinos
Journal: Circulation (2024)

Background: Endotrophin, a peptide derived from the COL6A3 chain that is released during COL6 formation, has been associated with cardiorenal outcomes in human observational studies and has demonstrated a strong association with adverse outcomes in heart failure with preserved ejection fraction. Endotrophin may modulate various biologic processes, but its potential causal cardiovascular effects are at present poorly understood. Research Questions/Aims: We aimed to investigate the potential causal effects of COL6A3-derived endotrophin on cardiorenal outcomes in humans, and its mediating mechanisms. Methods: Using genetic summary data from the UK Biobank (Olink, N=51,637) and deCODE (SOMAScan, N=35,365) studies, we first validated genetic instruments for COL6A3-derived endotrophin. We then leveraged those genetic instruments to investigate the effects of endotrophin inhibition on primary cardiorenal outcomes, including coronary artery disease, abdominal aortic aneurysm (AAA), chronic kidney disease, and heart failure (HF). Results informed our secondary analyses, where we investigated the effects of endotrophin on pulse pressure and aortic diameter. Next, using independent genetic association summary statistics (N=200,000-1,000,000), we explored the human proteome to gain insights into mechanisms of action, and the human phenome to assess the widespread health implications of COL6A3-derived endotrophin. We adjusted for multiple comparisons using the false discovery rate method. Results: MR findings revealed a significant association between COL6A3-derived endotrophin inhibition and reduced risk of HF (OR=0.60; 95%CI=0.51, 0.77) and AAA (OR=0.49; 95%CI=0.31, 0.77). Proteome-wide MR suggested that genetically proxied COL6A3-derived endotrophin inhibition was significantly associated with reduced COL28A1 (β=-0.71; 95%CI= -0.88, -0.53) and MAM domain containing-2 (MAMDC2; β=-0.71; 95%CI=-0.84, -0.57) levels. Phenome-wide association MR analyses suggested that genetically proxied COL6A3-derived endotrophin inhibition was associated with reduced risk of thoracic aortic aneurysm (OR=0.35, 95%CI=0.21, 0.59) and bronchiectasis (OR=0.26, 95%CI=0.14, 0.48). Conclusions: This is the first study to validate genetic instruments for COL6A3-derived endotrophin, and to provide genetic evidence supporting a causal role for endotrophin on HF and AAA risk. Clinical trials are required to further explore the effect of pharmacologically perturbing COL6A3-derived endotrophin levels.