tbuckley/cabot-search huggingface dataset:
Abstract 4142193: Emerging Role of Sodium-glucose cotransporter-2 Inhibitors in the Management of Chemotherapy-Related Cardiac Dysfunction: A Systematic Review and Meta-analysis
Authors: Mansoor Rahman, Ahmad Alayyat, Junaid Ali, Hamza Asif, Waqas Ullah, Deepak Bhatt
Journal: Circulation (2024)

INTRODUCTION: Many anti-cancer agents, including alkylating, anthracycline-based, and anti-HER2 chemotherapies, have a high risk of causing clinically significant cardiac toxicity, manifesting as heart failure (HF). The efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i's) in HFrEF and HFpEF is well-established; their role, however, in managing chemotherapy-related cardiac dysfunction (CTRCD) remains unclear. AIMS: To analyze available data on the efficacy of SGLT2i's in CTRCD. Methods: Pubmed, Embase and Web of Science databases were queried to find relevant clinical studies on the use of SGLT2i's in CTRCD. Primary outcomes included HF incidence, HF exacerbations, and all-cause mortality. Using a random effects model, relative risk ratios (RRs) with 95% confidence intervals were computed for all outcomes. Results: Out of 807 retrieved citations, 4 observational studies with 6576 participants were included in the analysis. In SGLT2i's and non-SGLT2i's groups, the number of subjects, mean age, and proportion of males were 1551 vs. 5025, 67.6 vs. 68.9 years, and 42% (648) vs. 40% (2000) with median follow-up range of 1.5-3.4 years. Only one study enrolled patients with prior HF, while diabetes was common among all. Anthracyclines were the most common chemotherapy agents used and the majority of patients had a hematological malignany. Onset of HF in the SGLT2i's group, as reported by two studies, was 6/31 and 94/930 in the non-SGLT2is group. The pooled HF incidence rate was similar between the two groups, with an RR of 0.54 (0.25-1.16, p=0.11). SGLT2i's users had a significantly lower rate of HF exacerbations and all-cause mortality compared with those who did not receive SGLT2i's with RR of 0.54 (0.33-0.91, p=0.02) and 0.48 (0.32-0.73, p=0.0006), respectively. Additionally, SGLT2i's were associated with a significantly lower rate of arrhythmias [ RR 0.40 (0.22-0.70, p=0.001)]. The mortality effect was beleived to be influenced by the antitumor effects of SGLT2i's as well. Moreover, the rates of adverse events secondary to SGLT2i's, such as euglycemic ketoacidosis, hypoglycemia, and infections, were reported to be lower. Conclusion: The observational data on the efficacy of SGLT2i's in CTRCD are promising. These drugs were found to have favorable effects on HF exacerbations, all-cause mortality, and arrhythmias onset associated with CTRCD. Large-scale randomized clinical trials are needed to validate these findings.
Abstract 4142346: EPAC2-expressing neurons within the stellate ganglia are responsible for cardiac sympathetic innervation
Authors: Yue-Yi WANG, Xinyu Liu, Yu Chen, Gang Cao, Hong Jiang, Lilei Yu
Journal: Circulation (2024)

Background: Neurons located in the stellate ganglia (SG) are responsible for providing sympathetic nerve supply to the heart. This innervation plays a role in cardiac sympathetic overactivity, which can lead to malignant ventricular arrhythmias and chronic cardiac remodeling during disease processes. However, the specifics of how SG contributes to cardiac innervation are still not well understood. Methods: We used retrograde neuroanatomical tracing and immunofluorescence assays to confirm the presence of cardiac-innervating neurons, specifically the exchange protein directly activated by cAMP 2 positive (EPAC2+) neurons in the SG. Subsequently, single nucleus RNA sequencing was performed to determine the transcriptional profiles of SG cells, including EPAC2+ neurons. Additionally, we evaluated the physiological function of EPAC2+ neurons in healthy dogs and in an acute myocardial infarction (MI) model induced by occlusion of the left anterior descending artery. To explore the pathological role of EPAC2+ neurons in cardiac remodeling, we used a chronic MI model with neuron-specific adeno-associated virus (AAV). Results: We identified EPAC2+ neurons within the SG that specifically innervate the heart. These EPAC2+ neurons exhibited a unique transcriptional profile compared to EPAC- neurons, with a notable enrichment in genes involved in the calcium signaling pathway, including calcium channels and adenylyl cyclases 8 and 9 (AC8 and AC9). Functionally, activation of EPAC2 in the SG led to increased sympathetic activity. Inhibition of EPAC2 specifically reduced SG nerve activity and prevented ventricular arrhythmias following acute myocardial infarction. Moreover, targeted knockdown of EPAC2 in neurons diminished SG hyperactivity, enhanced cardiac function, reduced sympathetic nerve sprouting at the infarct border zones, and decreased ventricular remodeling after MI, while reversing the phosphorylation of MEK1/2 and ERK1/2. Conclusions: The results indicate that EPAC2+ neurons in the SG play a crucial role in heart innervation. This research enhances our understanding of cardiac sympathetic innervation and could lead to new therapeutic approaches.
Abstract 4142234: First-in-Human Multi-Perspective Mapping Approach Offers Mechanistic Insights in Atrial Fibrillation
Authors: Andrew Nguyen, Ian Ling, Matthew Chen, Rod Partow-Navid, Steven Leung, Andrew Zadeh, Ivan Ho, Junaid Zaman
Journal: Circulation (2024)

Introduction: The mechanisms underlying the persistence of atrial fibrillation (AF) are still debated. Studies in animal and human cardiac bench top models suggest that different mapping techniques influence the detection of localized sources or self-sustaining, transient wavelets in AF. Despite this, no human studies have examined the influence of a local versus global mapping approach on the detection of these sources simultaneously in the same patient. Objective: We hypothesize that local and global mapping of AF offer different spatiotemporal resolutions that influence the nature of sustaining mechanisms but not their location in the chamber. This will be particularly evident for rotational sources. Methods: 16 patients who underwent catheter ablation for AF, atrial flutter (AFL), or premature atrial contractions (PACs) were studied. All patients underwent electroanatomic mapping of the left and right atria with both local and global approaches. Anatomical locations were subdivided into different regions (Figure 1A, 1B). Mechanisms were classified as focal, rotational, or localized irregular activation (LIA) using mapping algorithms. Analyses were done using Chi-squared tests. Results: A total of 40 AF, 12 AFL, and 4 PAC simultaneous electroanatomic maps were obtained. Both local and global mappings identified an AF source (n=52) within close anatomical proximity 86.5% of the time ( p &lt;0.001). However, mechanisms differed between AF sources identified with different views (34.6% same, 65.4% different, p =0.03) (Figure 1C). These different mechanisms were 47.1% rotational and 50% LIA on global maps (n=34, p &lt;0.001) and 94.7% focal on local maps (n=19, p &lt;0.001) (Figure 1D). AF sources with the same activation pattern across different scales were mostly identified as focal (94.4%, p &lt;0.001). In contrast, AFL and PACs shared both location (100%, p =0.005) and mechanism (87.5%, p =0.03) across local and global maps. Conclusion: Local and global maps offer different spatiotemporal resolutions that influence how a mechanism of a source is portrayed, and hence ablation strategy. This has a greater impact on rotational sources in AF, and may explain the divergent results in pre-clinical and clinical AF mapping studies.
Abstract 4142363: Pattern-Recognition Receptor-Associated Thromboinflammatory Transcript Changes in Platelets and Leukocytes
Authors: Jason Core, Heather Corkrey, Jeffrey Rade, Robert Finberg, Jennifer Wang, Kahraman Tanriverdi, Jane Freedman, Milka Koupenova
Journal: Circulation (2024)

Background: Increased risk of thrombotic outcomes has been observed during respiratory infections. This phenomenon likely involves platelet-leukocyte crosstalk via pattern recognition receptors (PRRs), including Toll-like receptors (TLR), Retinoic acid-inducible gene I-like receptors (RLR) and cGAS. Purpose: We studied correlations between PRRs and select pro-thrombotic/procoagulant transcripts (ITGA2B, GP1BA, GP9, GP5, GP6, PF4, PF4V1, F13A1, SELP, SERPING1) in platelets and leukocytes of COVID19 (α-δ variants) patients; and determined if those correlations were present in blood from patients with 3 respiratory infections (COVID19, Influenza, Tuberculosis-TB). Methods: RNA sequencing data of platelets and leukocytes isolated from COVID19 patients (n=10) and non-infected controls (n=15) was generated using AmpliSeq. Whole blood RNAseq was obtained from public databases for COVID19 (GSE217948), influenza (GSE161731), and TB patients (0m-peak infection, GSE181143). Transcripts with significantly greater mean expression in infected patients versus the respective control were assessed for positive correlations with PRRs using Spearman’s correlation coefficients. Data was analyzed in R. Results: Platelets and leukocytes showed distinct patterns of the top five highest expressed PRRs, based on BaseMean (Platelets: TLR9&gt;DDX58&gt;IFIH1&gt;CGAS&gt;TLR4, Leukocytes: TLR4&gt;IFIH1&gt;DDX58&gt;TLR8&gt;TLR2). PRR that were significantly increased in COVID19 platelets versus controls were DDX58 (p=0.017) and IFIH1 (p=0.005); in leukocytes only IFIH1 (p=0.015) showed significant difference. The only overlapping correlation between a PRR and transcript in the two cell populations was TLR1 with F13A1 (platelets, R=0.56, p=0.04; leukocytes, R=0.56, p=0.02). In COVID19 platelets, TLR9 correlated with GP1Ba (R=0.62, p=0.002); DDX58 correlated with GP9 and PF4; and IFIH1 correlated with GP9 and GP6. In COVID19 leukocytes, IFIH1 and DDX58 correlated with SERPING1. In whole blood RNAseq analysis of all 3 infections, only DDX58 and TLR1 uniformly associated with PF4 and F13A1, respectively. Surprisingly, correlations between PRRs and the listed transcripts overlapped predominantly between COVID19 and acute TB, but not with influenza. Conclusion: Platelets and leukocytes show distinct patterns of PRR expression and correlations with pro-thrombotic/procoagulant transcripts. Whole blood correlations between PRRs and thrombotic transcripts in COVID19 infection demonstrate more overlap with TB than influenza.
Abstract 4142194: Comparative Characteristics and Outcomes of Primary Compared to Glycogen Storage Disease-Associated Hypertrophic Cardiomyopathy
Authors: Spandan Desai, Nicholas Roma, Megan Pattoli, Matthew Durkin, Brian Henstenburg, Lindsey Magid, Vikas Yellapu, Luke Miller, Jamshid Shirani
Journal: Circulation (2024)

Background: Glycogen storage disease (GSD), characterized by defects in carbohydrate metabolism, may result in left ventricular hypertrophy (GSD-CM) that mimics primary hypertrophic cardiomyopathy (HCM). Differentiation of GSD-CM and HCM relies mostly on genetic testing. We aimed to evaluate differences in demographics, comorbidities and in-hospital outcomes of GSD-CM compared to HCM. Methods: National Inpatient Sample 2016-2021 was used to identify adults with GSD-CM and HCM using appropriate ICD codes. Logistic regression was applied to compare in-hospital outcomes. Results: From 2016-2021, 110 GSD-CM and 333,685 HCM adults were admitted. Most common admitting or principal diagnoses in the GSD-CM group were acute on chronic heart failure (23.8%) and pneumonia (14.3%). In comparison to HCM, GSD-CM cases were younger (44.3 -vs- 66 years), more likely to be males (66.7% -vs- 44.1%, p&lt;0.001) and less likely to be caucasians (40.0% -vs- 67.6%, p&lt;0.001). Most common causes of GSD were observed to be Pompe disease (50 cases) and von Gierke disease (25 cases). As shown in Table 1, despite GSD-CM cases having lower proportions of comorbidities including hypertension, diabetes mellitus, coronary artery disease, hyperlipidemia, and chronic kidney disease, GSD-CM had a longer length of stay (LOS) as compared to HCM (12.9 -vs- 5.9 days, p&lt;0.001). GSD-CM also had a higher total hospital cost compared to HCM ($261,167 -vs- 87,246) and higher rates of in hospital complications such as mortality (4.8%-vs-3.5%, p=0.037), cardiogenic shock (9.5% -vs- 2.6%, p&lt;0.001) and need for heart transplant (9.5% -vs- 0.2%, p=0.041). Conclusion: This retrospective database analysis comparing GSD-CM with HCM was indicative of higher prevalence amongst younger males and resulted in higher mortality, higher in-hospital complication rate, prolonged LOS, and increased total cost of hospitalization. While the overall proportion of GSD-CM compared to other cardiomyopathies remains low, this particular subset of patients warrants further study to better understand long-term outcomes.
Abstract 4142700: Inverse decremental conduction in the left bundle following cardiac surgery: potential clinical implications
Authors: Stefano Pacifici, Filip Istvanic, Yubin Zhang, Carlos Ceron, Farah Olleik, Tong Liu, Chuanyu Gao, Gan-Xin Yan
Journal: Circulation (2024)

Background: New onset left bundle branch block (LBBB) is the most common complication following transcatheter aortic valve replacement (TAVR), occurring in up to 35% of cases. Previous case studies have shown that in some patients with new onset LBBB, the QRS duration is positively correlated with the preceding RR interval. This unique phenomenon, known as inverse decremental conduction (IDC) or Yan conduction, prompted us to investigate its clinical features and implications. Methods: We reviewed 12-lead ECGs and available in-patient telemetry for patients with new onset LBBB within 14 days following any types of cardiac surgery from 2018 to 2023 at two medical centers. Patients with ≥3 different degrees of LBBB in response to different preceding RR on 12-lead ECGs or on telemetry were included in the analysis. Results: A total of 22 patients (19 males) with a mean age of 75±8 years were identified to exhibit varying degrees of LBBB, with QRS duration that was positively correlated to the preceding RR interval within a certain range of heart rates. Among these patients, 17 had undergone TAVR, while the remaining 5 underwent surgical aortic valve replacement (AVR) and/or mitral valve replacement. 13 of the 22 patients were in sinus rhythm with premature atrial beats or sinus arrhythmias, while the remaining 9 patients were in atrial fibrillation. Figure 1 shows the typical manifestations of IDC in the left bundle on ECG in a patient post TAVR, with a positive correlation between QRS duration and the preceding RR (r = 0.87, p &lt; 0.01). IDC in the left bundle in patients with new-onset LBBB occurred within three days following cardiac surgeries in 20 of the 22 patients, while the remaining 2 patients exhibited IDC in the left bundle &gt; 7 days after the surgeries. IDC in the left bundle is a temporary phenomenon, commonly lasting &lt;24 hours in most cases, and evolving into either a normal QRS or permanent LBBB. Interestingly, alternating LBBB occurred in 5 patients with IDC in the left bundle as shown in Figure 2 . Conclusion and Comment: 1) there is a positive correlation between the preceding RR interval and QRS duration, indicating IDC in left bundle, in the patients with new onset of LBBB following cardiac surgeries particularly AVR; 2) this unique phenomenon is often short-lived; 3) theoretically, IDC in left bundle can translate into PR interval changes consistent with IDC in patients with preexisting right bundle branch block, leading to paroxysmal AV block.
Abstract 4142252: Impact of Diagnosis to Ablation Time on Recurrence of Atrial Fibrillation and Clinical Outcomes after Catheter Ablation: A Systematic Review and Meta-analysis with Reconstructed Time-to-Event Data.
Authors: Ahmed Mazen Amin, Hossam Elbenawi, Ubaid Khan, Omar Almaadawy, Mustafa Turkmani, Wael Abdelmottaleb, Mohammed Essa, Mohamed Abuelazm, Basel Abdelazeem, Zain Ul Abideen Asad, Abhishek Deshmukh, Christopher Desimone
Journal: Circulation (2024)

Background: Current clinical guidelines emphasize the significance of rhythm control with catheter ablation but lack guidance on the timing after diagnosing atrial fibrillation (AF). Purpose: We aim to investigate the latest evidence on the impact of diagnosis to ablation time (DAT) on AF recurrence, all-cause mortality, stroke, and heart failure (HF) after AF catheter ablation. Methods: We comprehensively searched PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through February 2024. We conducted a pair-wise and prognostic systematic review and meta-analysis with a reconstructed time-to-event data meta-analysis. All analyses were performed using R V. 4.3.1. PROSPERO ID: CRD42024525542. Results: With the inclusion of 22 studies, our cohort comprised a total of 42,101 patients. Regarding pair-wise meta-analysis, shorter DAT was significantly associated with a decreased incidence of AF recurrence across paroxysmal and persistent AF subgroups. Moreover, DAT ≤ one year was significantly associated with a decreased incidence of all-cause mortality (RR: 0.73 with 95% CI [0.59, 0.92], P&lt; 0.01) with a trend toward lowering the risk of stroke (RR: 0.80 with 95% CI [0.62, 1.03], P= 0.08). However, there was no significant difference between DAT ≤ one year and DAT &gt; one year in HF. Regarding adjusted prognostic meta-analysis, longer DAT was significantly associated with an increased risk of AF recurrence (P &lt; 0.01). Our reconstructed Kaplan Meier showed that DAT &gt; one year was significantly associated with a 50% increase in the risk of AF recurrence compared to DAT ≤ one year (HR: 1.50 with 95% CI [1.42, 1.58], P&lt; 0.00001) over 60 months follow-up. Conclusion: Our meta-analysis strongly underscores the critical importance of a short DAT in significantly reducing AF recurrence and all-cause mortality, with a trend toward lowering stroke risk, though no significant impact on HF was observed. Early ablation proves beneficial not only for patients with paroxysmal AF but also for those with persistent AF. These findings suggest that minimizing DAT can markedly improve AF outcomes, warranting further investigation to optimize treatment strategies.
Abstract 4142289: Abatacept Drug-Induced Loeffler Endocarditis: A Manifestation of Hypereosinophilic Syndrome
Authors: Alexander Sweeting, Michael Atalay, Saurabh Agarwal, Edward Hulten, Yash Patel
Journal: Circulation (2024)

Description of Case: This case presents a 32-year-old woman with history of rheumatoid arthritis who presented with symptoms of worsening dyspnea on exertion, fatigue, and stable angina five weeks after starting abatacept. Methods: Performed a comprehensive retrospective analysis of one patient's medical history, clinical presentation, diagnostic assessment, therapeutic intervention, and clinical outcome. Results: Physical exam was remarkable for signs of volume overload. Electrocardiogram showed sinus tachycardia and diffuse nonspecific T-wave inversions. Laboratory studies revealed a complete blood count significant for eosinophilia of 26,000, representing 79.5% of the differential. Troponins were negative. A brain natriuretic peptide was 903 pg/ml. Echocardiogram findings included mild reduction in biventricular systolic function with wall motion abnormality seen at the apex. Cardiac MRI (CMR) demonstrated mild biventricular systolic dysfunction, left ventricular intracavitary filling defect consistent with thrombi, and diffuse biventricular subendocardial late gadolinium enhancement (LGE) consistent with fibrosis. Abatacept was stopped with resolution of eosinophilia. Patient was treated with a short course of steroids and initiated on warfarin for left ventricular thrombi. Repeat CMR four months later showed resolution of left ventricular thrombi and biventricular dysfunction, with persistence of diffuse subendocardial fibrosis in both left and right ventricles. Discussion: CMR demonstrates findings consistent with Loeffler Endocarditis as evident by ventricular intracavitary filling defects and diffuse biventricular subendocardial late gadolinium enhancement. Initial management of involves prompt discontinuation of the suspected offending drug. Corticosteroids may be employed to mitigate eosinophilic infiltrate and myocardial inflammation. Diagnostic modalities such as cardiac imaging, endomyocardial biopsy, and laboratory testing play crucial roles in confirming the diagnosis and assessing severity. Follow-up CMR can help follow the response to cessation of the offending agent and rule-out confounding disease processes, as seen in this case. In conclusion, abatacept-induced eosinophilic endocarditis is a rare phenomenon that is poorly understood. Drug-induced eosinophilic endocarditis should be considered as a differential in patients that develop heart failure symptoms and eosinophilia after initiating abatacept.
Abstract 4142355: Effect of Testosterone Replacement Therapy on Cardiovascular Outcomes in Males: a meta-analysis of Randomized Controlled Trials
Authors: Teebro Paul, Rohan Kaza, Hadii Mamudu, Dihan Thilakaratne, Jimmy Kerrigan
Journal: Circulation (2024)

Background: Available data on the effects of testosterone replacement therapy (TRT) on cardiovascular (CV) events and all-cause mortality have yielded conflicting results. There is scarcity of data from large prospective randomized controlled trials in this regard. The objective of this meta-analysis is to compare all-cause mortality and cardiovascular outcomes in patients with and without TRT. Methods: PubMed database and Google Scholars was searched through May 2024 for articles meeting the eligibility criteria. We included randomized controlled trials (RCTs) with a sample size of at least 100 patients and a follow-up of more than 12 months. The end points were all-cause mortality, CV mortality, myocardial infarction (MI), stroke, and any CV event. The Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI) was computed with Random Effects model and p&lt;0.05 was considered as a level of significance. RevMan 5.4 software was used for the analysis. Results: There were twelve studies (n=8,636) comparing CV outcomes and all-cause mortality among patients with hypogonadism treated with TRT (n=4,336) vs control groups (n=4300). There was no significant heterogeneity observed with the outcomes. There was no significant difference in MI (OR 1.11; CI 0.79-1.55), stroke (OR 1.02; CI 0.67-1.53), any CV events (OR 0.94; CI 0.62-1.43), CV mortality (OR 0.88; CI 0.0.66-1.16), and all-cause mortality (OR 0.86; CI 0.49-1.49) between TRT and control groups. Forest plots (Figure 1 and Figure 2) showed MI and any cardiovascular events, respectively. Conclusion: There was no significant difference in CV outcomes and all-cause mortality in patients treated with TRT as compared to controls. However, large RCTs with a long-term follow-up are needed to evaluate these findings.