tbuckley/cabot-search huggingface dataset:
Abstract 4145140: Wenckebach conduction from ventricular endocardium to epicardium induced by class Ic I <sub>Na</sub> blockers: implications for mechanical dysfunction and arrhythmias
Authors: Yuan Gao, Datun Qi, Wenping Zhao, Tong Liu, Mingjun Zhu, Chuanyu Gao, Gan-Xin Yan
Journal: Circulation (2024)

Background: It is known that the Class Ic antiarrhythmic drugs exhibit strong use-dependent blockade of fast sodium current (I Na ) due to their slow dissociation kinetics from the sodium channel. Clinically, Class Ic I Na blockers are linked to increased mortality in patients with coronary artery disease or ventricular systolic dysfunction. However, the mechanisms by which Class Ic I Na blockers influence ventricular conduction and mechanical function, thereby contributing to increased mortality, have not been well studied. We hypothesized that Class Ic I Na blockers may transition conduction of normal ventricular myocytes from an "all-or-none" pattern to Wenckebach or decremental conduction, features typically associated with slow response action potentials (APs). This change could markedly alter ventricular electrophysiology and mechanical function. Methods: APs, with ECG and contractility, were recorded concurrently from ventricular epicardium (Epi) and endocardium (Endo) in the isolated arterially perfused rabbit ventricular wedge in control and in presence of flecainide, a class Ic I Na blocker, at 10 microM. The preparations were paced from Endo at basic cycle lengths (BCL) ranging from 300 to 1000 ms. Results: Pacing from a BCL of 1000 ms down to BCLs of 300 to 600 ms resulted in decremental conduction between the ventricular Endo and Epi during pacing rate acceleration or Wenckebach conduction at a constant rapid pacing rate in the presence of flecainide. This unique conduction (Figure 1) was observed in 8 of 8 preparations under flecainide perfusion versus 0 of 8 in the control perfusion (p&lt;0.01). Decremental and Wenckebach conduction was always associated with reduced and dyssynchronous contraction. Additionally, flecainide blunted or even reversed physiologically positive staircase response of contractility (Figure 2). Notably, 2 to 1 conduction and paroxysmal conduction block between the Endo and Epi occurred in 4 of 8 (Figure 3). On the other hand, conduction delay between the ventricular Endo and Epi also promoted echo beats and non-sustained ventricular tachycardia via a reentrant mechanism. Conclusions: Flecainide due to its strong use-dependent blockage of I Na has a capability to transition ventricular fast response APs to slow response APs, leading to Wenckebach or decremental conduction. This conduction not only reduces ventricular contraction but also induces dyssynchrony. Intraventricular conduction block also promotes reentrant arrhythmias.
Abstract 4145163: Postprocedural Anticoagulation Following Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Meta-Analysis of Clinical Outcomes
Authors: Vinicius Oliveira, Natalia Gaban, ARIADNE SILVA, Lucca Lopes, Pedro Lucas Alves Alencar, Ana Paula Duarte Lima, Izadora Oliveira, Humberto Graner Moreira
Journal: Circulation (2024)

Background: The use of procedural anticoagulation during primary percutaneous coronary intervention (PCI) is well established and has been shown to improve clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Despite its widespread application in clinical settings, the necessity and efficacy of postprocedural anticoagulation (PPA) remain contentious. Thus, this is the first meta-analysis to assess the efficacy and safety of PPA after PCI for the management of STEMI. Methods: A comprehensive search of PubMed, Cochrane, and Embase databases was conducted to identify studies comparing the clinical outcomes between PPA administration and control (placebo or no anticoagulant infusion) following PCI for STEMI treatment. Statistical analyses were performed using RevMan version 5.4.1, employing a random-effects model to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Results: A total of four studies comprising 45,066 patients were included (2 RCTs and 2 non-randomized studies), of which 30,925 (68.6%) received PPA. Among the included patients, 35,770 (79.4%) were female. Compared to the control group, PPA did not significantly reduce all-cause mortality (OR 0.82; 95% CI 0.49 – 1.36; P=0.44), cardiac death (OR 0.81; 95% CI 0.49 – 1.33; P=0.41), and major adverse cardiovascular events (MACE) (OR 0.97; 95% CI 0.64 – 1.47; P=0.88; Figure 1A). Moreover, the odds of stent thrombosis (OR 1.24; 95% CI 0.92 – 1.68; P=0.15), myocardial infarction (OR 1.03; 95% CI 0.79 – 1.36; P= 0.81) and stroke (OR 0.95; 95% CI 0.41 – 2.20; P=0.90) did not differ between the groups. However, patients receiving PPA were associated with higher odds of TIMI major/minor bleeding (OR 1.49; 95% CI 1.20 – 1.84; P&lt;0.01; Figure 1B). Conclusions: This meta-analysis reveals no significant differences in the odds of all-cause mortality, cardiac death, MACE, stent thrombosis, myocardial infarction and stroke between PPA and control following PCI for the management of STEMI. However, PPA was associated with higher odds of TIMI major/minor bleeding when compared to control. Further randomized controlled trials are warranted to corroborate these findings.
Abstract 4144926: Central Sleep Apnea with Ticagrelor in Patients with Coronary Syndrome; A Meta-Analysis.
Authors: Abhigan Shrestha, Nischal Mainali, Kripa Rajak, Aman Goyal, Bimarsh Acharya, Randhir Yadav
Journal: Circulation (2024)

Background: Sleep apnea is characterized by cessation of breathing during sleep. It is often prevalent among patients with cardiovascular disorders. Ticagrelor, an anti-platelet drug, can have significant implications on the health of a patient. It is suspected to have potential impacts on sleep including sleep apnea. However, the extent of the association between ticagrelor and sleep apnea is unclear. Hypothesis: This meta-analysis evaluates the association between ticagrelor and the association of sleep apnea compared to placebo. Method: We systematically searched for relevant articles published until March 2024, on PubMed, Google Scholar and Embase. Odds ratios (OR) were pooled using the random-effects DerSimonian-Laird model, and a p-value of &lt;0.05 was considered statistically significant. Result: A total of four observational studies were included in the analysis. The use of ticagrelor was associated with increased odds of sleep apnea [OR 4.16, (95% CI: 2.63-5.70), I 2 =0.00% p=0.00] with statistical significance. Conclusion: The use of ticagrelor is associated with a significant increase in the risk of sleep apnea compared to placebo. Thus, there should be careful consideration of the risk of sleep apnea when prescribing ticagrelor. Despite these findings, further large-scale studies are warranted to justify these results in larger sample sizes.
Abstract 4145057: From Infection to Innovation: Leadless Pacemakers Implantation Following Infected Cardiovascular Implantable Electronic Device Extraction - An Updated Systematic Review
Authors: Bilawal Nadeem, Amel Fatima, Surik Sedrakyan, Ali Ahmed, Mirza Mehmood Ali Baig, Mifrah Rahat Khan Sherwani, John Wylie
Journal: Circulation (2024)

Introduction: Cardiovascular Implantable Electronic Device (CIED) infection is class I indication for complete transvenous lead removal (LR). The reimplantation strategies post-LR, especially in pacemaker-dependent patients or those necessitating cardiac resynchronization therapy (CRT) and/or implantable defibrillators, remain complex. Considering the limitations and risks associated with traditional approaches, the exploration of alternative devices such as leadless pacemakers (LP) have garnered attention due to their purported lower infection risk. Methods: We meticulously reviewed literature sources including PubMed, Scopus, and Embase utilizing a combination of search terms. The inclusion criterion was LP implantation post-LR of infected CIED, while the exclusion criterion was LR for noninfectious indications. Study endpoints encompassed patients’ outcomes during follow-up. Results: Our literature review yielded 818 articles, of which 21 met the inclusion criteria, encompassing a cohort of 612 patients who underwent LR followed by LP implantation (Table 1). A total of 250 (40.8%) patients underwent concurrent LP implantation during the LR procedure. The rest underwent staged procedures and the overall duration between LR of infected CIED and LP implantation was 4.32 ± 3.9 days. In our cohort, 172 (28.1%) patients had systemic CIED infections, whereas 130 (21.2%) had isolated pocket infections, with Staphylococcus aureus as the predominant causative organism in 96 (39.3%) cases. Procedural complications were scarce. Over a mean follow-up period of 13.2 ± 8.1 months, pacemaker syndrome was observed in 3 (0.67%) patients, while 1 (0.16%) patient had a re-infection related to LP. Conclusion: The remarkably low incidence of complications and re-infections following LP implantation underscores its potential utility as a viable implantation option after LR, particularly in pacing-dependent patients at higher risk of CIED infections.
Abstract 4144929: Electronegative VLDL Impairs Mitochondrial Function and Promotes Cardiomyocyte Dysfunction in Heart Failure with Preserved Ejection Fraction
Authors: Huan-Hsing Chiang, Omer Akyol, Ming-Hsien Tsai, Camila Hochman, Jody Vykoukal, Johannes Fahrmann, Darren Woodside, Deepak Bhatt, Chu-Huang Chen
Journal: Circulation (2024)

Background: Heart failure with preserved ejection fraction (HFpEF) affects energy metabolism, increasing reliance on long chain fatty acids (LCFA). Alterations to VLDL, the main triglyceride transporter, may significantly influence disease progression. VLDL can be separated into 5 subfractions from V1 (most beneficial, least electronegative) to V5 (most electronegative). This study investigates whether VLDL electronegativity induces cardiomyocyte dysfunction through changes in cellular metabolism. Goals: We aim to explore the cellular mechanisms of V5-induced pathology in rat neonatal cardiomyocytes (RNC) and bovine aortic endothelial cells (BAEC), potentially accelerating the systemic inflammation that leads to the development of HFpEF. Methods: V1 and V5 were isolated from healthy blood bank donors. RNCs were treated with PBS (control), V1, or V5 at 25 or 50 µg/mL for 24 hours. Mitochondrial function was evaluated using the Seahorse ATP production rate, cell mito stress, and palmitate oxidation stress test assays. Immunofluorescence staining of RNCs and BAECs was performed to elucidate systemic inflammation. Comprehensive lipidomics characterized components potentially involved in V5’s cytotoxic effects. Results: For RNCs treated with V5, ATP production shifted remarkably towards glycolysis instead of oxidative phosphorylation ( Figure A ). V5 but not V1 severely impaired mitochondrial respiration, affecting basal respiration, spare respiratory capacity, and maximal respiration in a concentration-dependent manner ( Figure B ). When LCFA transport into mitochondria is blocked, V5-treated RNCs showed increased cellular uptake of palmitate, leading to heightened lipotoxicity. In both RNCs and BAECs, V5 but not V1 reduced cell viability and increased apoptosis ( Figure C ). Lipidomic studies revealed that compared to V1, V5 contains multiple glycated lipid components and a richer triglyceride content. Conclusion: We report novel findings that increased VLDL electronegativity provokes mitochondrial dysfunction through energy depletion and lipid overload, resulting in cardiomyocyte impairment. This explains how V5-rich VLDL, observed in metabolic syndrome, contributes to systemic inflammation and clinically manifests as HFpEF.
Abstract 4145151: In-Flight Sudden Cardiac Arrest and Automated External Defibrillator Use
Authors: Mario Bassi, Matthew Kuchtaruk, Nathan Jiang, Cameron Sartor, Adrian Baranchuk
Journal: Circulation (2024)

Background: In-flight cardiac arrest (IFCA) is unique due to restricted access to equipment, healthcare providers, and isolated location in the air. This review aimed to explore the complexities surrounding IFCA on commercial flights, including the prevalence, incidence, and risk factors of IFCA and the effectiveness of automated external defibrillators (AED). Methods/Results: A narrative review of the literature was conducted on MEDLINE, PubMed, EMBASE, and Google Scholar. Literature searches were completed with Medical Subject Headings (MeSH), Emtree terminology, and appropriate keywords. The applied terms included “sudden cardiac arrest” OR “sudden cardiac death” OR “cardiac arrest, out of hospital” OR “cardiopulmonary resuscitation” OR “defibrillators” and a combination of “aircraft” OR “aviation”. IFCA accounts for approximately 0.3% of all in-flight emergencies yet is responsible for up to 86% of all in-flight deaths. The most recent literature shows an overall survival rate from IFCA of 44%; with shockable and non-shockable rhythm survival at 53% and 35%, respectively. Table 1 summarizes reports of IFCA incidence and survival. The most impactful risk factors for IFCA included male sex (79%) and past cardiac history (48.5%). Age was not found to be a significant predictor of IFCA. Thought to be due to in-flight immobility and venous stasis, pulmonary embolisms are reportedly responsible for 2% of IFCA. AEDs have been mandated on all commercial flights with at least 1 trained attendant in the US since 2004, however, they are only recommended in many parts of the world. A study analyzing the emergency medical equipment of European airlines showed that only 65% have provided an AED for their aircraft. Studies have shown a survival of IFCA to hospital admission of up to 36% in patients that received a shock from an AED compared to 6% without an AED. Even in non-shockable rhythms, 76% of AED applications were used for monitoring purposes and assisted with ongoing treatment. Conclusion: IFCA remains a rare yet highly fatal event that is associated with male sex, past cardiac history, and pulmonary embolism risk. Availability of AEDs and trained personnel are critical factors to treat patients presenting with IFCA.
Abstract 4145096: Postural Orthostatic Tachycardia Syndrome and Inappropriate Sinus Tachycardia – Two Distinct Phenotypes in Post-COVID-19 Cardiovascular Dysautonomia: Prevalence, Overlap and Clinical Characteristics
Authors: Maria Juszczyk, Artur Fedorowski, Marcus Stahlberg, Christian Lewinter, Sara Nawaz
Journal: Circulation (2024)

Introduction: Postural orthostatic tachycardia syndrome (POTS) and Inappropriate sinus tachycardia (IST) are common manifestations of cardiovascular dysautonomia (CVAD) in patients with post-COVID-19 syndrome. Studies regarding differences between post-COVID-19 POTS and post-COVID-19 IST have been sparse and based on small patient series. Aims: To examine clinical differences between POTS and IST in patients with post-COVID-19 syndrome. Methods: A cross-sectional observational study based on a dataset of patients diagnosed with post-COVID-19 syndrome and POTS/IST, at Karolinska University Hospital, Stockholm in 2020-2023, was performed. Data was retrieved using patients’ medical records. ANOVA, chi-square tests and Fisher’s exact tests were used for analysis. Results: A total of 200 patients diagnosed with post-COVID POTS/IST (ICD-10 codes, I.498 + U.099) were included (female, 85%) and divided into a POTS-group (n=110) and IST-group (n=90). Sixty-one patients (31%) met the diagnostic criteria of both and were included in the IST-group. The mean ages were 38 years for the POTS-group and 42 years for the IST-group (p=0.027). Hypertension was more common within the IST-group (p&lt;0.001). Of the entire study population, 73% developed their post-COVID-19 tachycardia after being infected by the SARS-CoV-2 virus in 2020. Non-cardiac symptoms were more common than cardiac symptoms and fatigue was the most frequently reported symptom amongst the entire study population, but both cognitive impairment (p=0.046) and nausea (p=0.020) were more commonly reported by the POTS-group. There was no significant difference regarding symptom burden according to Malmö POTS Score. Resting, average and maximum heart rate during 24-hour ECG monitoring were higher in the IST group compared to the POTS-group (89 vs. 78 bpm; 91 vs. 76 bpm; 157 vs.144; p&lt;0.001). Ivabradine was the most frequently prescribed pharmacological agent within the study population, but Pyridostigmine was more commonly prescribed within the POTS-group (44% of the POTS-group vs. 31% of the IST-group, p=0.047). Conclusions: The diagnosis of POTS is more common than IST in patients suffering from post-COVID-19 syndrome, and there is a 31% overlap of patients diagnosed with both. There are some significant clinical differences between the groups, but both groups share the same symptom burden. The most commonly prescribed pharmacological treatment is Ivabradine, and Pyridostigmine is more frequently used for POTS.
Abstract 4145103: Reduced Penetrance and Variable Expression of Dilated Cardiomyopathy Associated with Homozygous Truncating Variants of <i>NRAP</i> Gene
Authors: Aisha Alqahtani, Sahar Tulbah, Nadiah Alruwaili, Maarab alkorashy, DIMPNA CALILA ALBERT BROTONS, Samah Zarroug, Zuhair Al-Hassnan
Journal: Circulation (2024)

Dilated cardiomyopathy (DCM) is a clinical condition with tremendous diversity of etiology. In familial forms of DCM, there has been a compelling evidence of immense genetic heterogeneity that implicate various mechanisms. Recently, biallelic loss-of-function (LOF) variants in the nebulin-related-anchoring protein ( NRAP ) gene have been reported in an ultra-rare form of DCM inherited recessively. In this study, we sought to describe the clinical and genetic spectrum associated with NRAP variants in our highly consanguineous population. Genetic analysis with whole exome sequencing, conducted on consecutively recruited cases of DCM, identified 13 consanguineous families with 6 different LOF variants in NRAP . Segregation analysis detected 25 homozygous and 25 heterozygous individuals. Interestingly, only 18 of the 25 homozygous cases were symptomatic with a remarkable variability of age of onset (9 months to 47 years, median 5 years), of whom 9 cases died with a median age of death of 3 years (range: 9 months to 13 years). None of the heterozygous individuals was clinically symptomatic. Of note, 3 homozygous cases underwent heart transplantation at the ages of 8, 11, and 14 years who are alive with a follow up of 6 years, 3 years, and 3 months respectively. Our work illustrates a notable clinical variability of DCM associated with NRAP LOF variants. This observation suggests an underling complex mechanism of NRAP -related DCM that deviates from simple mendelian inheritance and plausibly implicates modifiers. The reduced penetrance and variable expression underscore the need of exercising precaution when counseling individuals and families found to have NRAP variants.
Abstract 4145001: Renal Outcomes of Staged Versus Concomitant Percutaneous Coronary Intervention and Transcatheter Aortic Valve Replacement: A meta-analysis
Authors: Veda Chanda, Vinicius Bittar, Pedro Carvalho, Philippe Garot
Journal: Circulation (2024)

Background: The impact of staged on renal outcomes percutaneous coronary intervention (PCI) in patients undergoing transcatheter aortic valve replacement (TAVR) is uncertain. Methods: MEDLINE, Embase, and Cochrane were systematically searched for studies comparing staged versus concomitant PCI in patients with aortic stenosis and coronary artery disease undergoing TAVR and PCI. A random-effects model meta-analysis calculates the odds ratio (OR) with a 95% confidence interval (CI). Our outcome of interest was the incidence of contrast-induced acute coronary injury (CI-AKI) and its respective stages. Results: 11 studies comprising 6,056 patients undergoing TAVR and PCI were included. Compared with concomitant PCI, staged PCI did not reduce the incidence of CI-AKI (OR 0.89; 95% CI 0.48-1.64; p=0.70; Figure 1). In a subgroup analysis, there was no difference between staged and concomitant PCI in the incidence of stage 1 CI-AKI (OR 1.99; 95% CI 0.38-10.47; p=0.70), stage 2 CI-AKI (OR 1.01; 95% CI 0.39-2.64; p=0.70), and stage 3 CI-AKI (OR 0.48; 95% CI 0.23-1.00; p=0.051). Conclusion: In patients undergoing TAVR, there was no difference between staged versus concomitant PCI in the incidence of contrast-induced nephropathy.
Abstract 4145154: A Pilot Study of Post-Discharge Atrial Fibrillation Using a Novel Mobile Electrocardiography Monitoring Device
Authors: Alexander Iribarne, Nirav Patel, David D'Alessandro, John DiMaio, Sanjeev Bhavnani, Vinay Badhwar, Partho Sengupta, Linda Johnson, Elzbieta Gajewska-Dendek, Robert Kramer, Ellen Moquete, Jonathan Hupf, Prezley Duncan, Efstathia Mihelis, Michael Borger, Andrew Muir, Vaughn Starnes, Albin Edegran, Kathleen Fenton, Wendy Taddei-Peters, Alan Moskowitz, Patrick OGara, Annetine Gelijns, John Alexander, A Gillinov, Emilia Bagiella
Journal: Circulation (2024)

Introduction: Post-operative atrial fibrillation (AF) is the most common arrhythmic complication after CABG. Following inpatient treatment, data on the frequency and duration of recurrent AF after hospital discharge remain sparse. Research Question: Do patients who experience in-hospital post-operative AF have recurrent arrhythmias in the 30 days post discharge? Goals: To characterize the burden of AF after hospital discharge using a wearable telemetry device. Methods: Patients enrolled in the CTSN PACeS trial were eligible for this sub-study. PACeS is a randomized trial of anticoagulation versus no-anticoagulation in patients with new-onset post-operative AF. Eligibility criteria include patients with new onset AF defined as AF &gt; lasting 60 minutes or recurrent AF episodes within 7 days after CABG and before hospital discharge. All patients in this sub-study wore a 3-lead mobile telemetry device upon hospital discharge that provided continuous beat-to-beat data for 30 days. For this analysis, an AF event was counted if it was at least 30 seconds in duration. Results: Forty-six patients participated in this sub-study. The mean age was 68.8 years, 21.7% were women, 78.3% White and 11% Hispanic. The mean and median device wear times were 23 and 29 days, respectively. The average total available analytic time (i.e., total time of interpretable electrocardiographic signal) was 20.3±3.3 hours/day. At least one episode of AF post-discharge was detected in 38 (82.6%) of patients. Among these, the median number of days in which patients had an episode of AF was 6. The mean duration of time in AF was 1.6±1.7 hours/day and the overall percent time in AF was 7.5%. Most patients (78.3%, n=36) had AF for &lt;10% of the recording time. Nearly all AF events occurred within the first two weeks post discharge (Figure). Conclusions: In this telemetry study, patients who developed postoperative AF within 7 days of CABG were found to have a modest burden of post discharge AF episodes, most frequently within the first 2 weeks. These preliminary data should be verified in larger prospective studies, and may help inform anti-thrombotic and other management decisions for patients who develop AF following CABG surgery.