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While no bigger than a poppy seed, a tick can latch onto its host for a meal and leave an infection that can cause years of debilitating symptoms. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about wants of men and women published in the previous issue.

Background: Ontologies are fundamental components of informatics infrastructure in domains such as biomedical, environmental, and food sciences, representing consensus knowledge in an accurate and computable form. However, their construction and maintenance demand substantial resources and necessitate substantial collaboration between domain experts, curators, and ontology experts. We present Dynamic Retrieval Augmented Generation of Ontologies using AI (DRAGON-AI), an ontology generation method employing Large Language Models (LLMs) and Retrieval Augmented Generation (RAG). DRAGON-AI can generate textual and logical ontology components, drawing from existing knowledge in multiple ontologies and unstructured text sources., Results: We assessed performance of DRAGON-AI on de novo term construction across ten diverse ontologies, making use of extensive manual evaluation of results. Our method has high precision for relationship generation, but has slightly lower precision than from logic-based reasoning. Our method is also able to generate definitions deemed acceptable by expert evaluators, but these scored worse than human-authored definitions. Notably, evaluators with the highest level of confidence in a domain were better able to discern flaws in AI-generated definitions. We also demonstrated the ability of DRAGON-AI to incorporate natural language instructions in the form of GitHub issues., Conclusions: These findings suggest DRAGON-AI's potential to substantially aid the manual ontology construction process. However, our results also underscore the importance of having expert curators and ontology editors drive the ontology generation process., (© 2024. The Author(s).)

Background: Among the most commonly known causes of hematospermia are infections in the genitourinary tract, but no study exists that has comprehensively investigated hematospermia in patients with acute epididymitis., Objectives: To assess the impact of hematospermia in patients with acute epididymitis and its association with clinical, microbiological, and semen parameters., Materials and Methods: Since May 2007, a total of 324 sexually active patients with acute epididymitis were recruited in a prospective cohort study. Patients received a comprehensive medical and sexual history, and clinical, sonographic, laboratory, and microbiological diagnostics. Antibiotic therapy was given according to European Association of Urology guidelines. Semen analysis was offered 14 days after the first presentation and initiation of therapy. Since 2013, a separate control group of 56 patients presenting with isolated hematospermia (= no other urogenital symptoms) was prospectively recruited, and differences between the groups were statistically evaluated., Results: Of 324 patients with acute epididymitis, 50 patients (15%) had self-reported hematospermia. This occurred with a median of 24 h before the onset of scrotal symptoms and was associated with significantly elevated prostate-specific antigen levels compared to 274 patients without hematospermia (3.1 vs. 1.8 ng/ml, p < 0.01). The two most common etiological pathogens were Escherichia coli and Chlamydia trachomatis, and the bacterial spectrum was comparable in both epididymitis subgroups (p = 0.859). Semen analysis at 14 days still showed hematospermia in 24% of patients associated with massive leukocytospermia. Compared to the hematospermia control group, the two epididymitis subgroups showed significantly increased inflammation markers (pH, leukocytes, and elastase), reduced sperm concentration, and reduced levels of alpha-glucosidase and zinc (always p < 0.01)., Discussion and Conclusion: In sexually active patients who develop acute epididymitis, self-reported hematospermia is evident in 15% of patients as early as one day before the onset of scrotal symptoms. Conversely, none of the 56 patients presenting with isolated hematospermia developed epididymitis within the next 4 weeks., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Since 1999, The Arabidopsis Information Resource (www.arabidopsis.org) has been curating data about the Arabidopsis thaliana genome. Its primary focus is integrating experimental gene function information from the peer-reviewed literature and codifying it as controlled vocabulary annotations. Our goal is to produce a "gold standard" functional annotation set that reflects the current state of knowledge about the Arabidopsis genome. At the same time, the resource serves as a nexus for community-based collaborations aimed at improving data quality, access, and reuse. For the past decade, our work has been made possible by subscriptions from our global user base. This update covers our ongoing biocuration work, some of our modernization efforts that contribute to the first major infrastructure overhaul since 2011, the introduction of JBrowse2, and the resource's role in community activities such as organizing the structural reannotation of the genome. For gene function assessment, we used gene ontology annotations as a metric to evaluate: (1) what is currently known about Arabidopsis gene function and (2) the set of "unknown" genes. Currently, 74% of the proteome has been annotated to at least one gene ontology term. Of those loci, half have experimental support for at least one of the following aspects: molecular function, biological process, or cellular component. Our work sheds light on the genes for which we have not yet identified any published experimental data and have no functional annotation. Drawing attention to these unknown genes highlights knowledge gaps and potential sources of novel discoveries., Competing Interests: Conflicts of interest: The author(s) declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Purpose: Despite recent advances in adapting the intensity of treatment for older patients with ALL, current protocols are associated with high rates of early deaths, treatment-related toxicity, and dismal prognosis. We evaluated inotuzumab ozogamicin and dexamethasone (Dex) as induction therapy in older patients with ALL within the German Multicenter Study Group for Adult ALL (GMALL)., Patients and Methods: The open-label, multicenter, phase II, INITIAL-1 trial enrolled 45 patients older than 55 years with newly diagnosed, CD22-positive, BCR::ABL -negative B-precursor ALL (B-ALL). Patients received up to three cycles of inotuzumab ozogamicin/Dex and up to six cycles of age-adapted GMALL consolidation and maintenance therapy., Results: Forty-three evaluable patients with common/pre-B (n = 38) and pro-B ALL (n = 5), with a median age of 64 years (range, 56-80), received at least two cycles of inotuzumab ozogamicin induction therapy. All patients achieved complete remission (CR/CR with incomplete hematologic recovery). Twenty-three (53%) and 30 (71%) patients had no evidence of molecularly assessed measurable residual disease (minimum 10e-4 threshold) after the second and third inductions, respectively. After a median follow-up of 2.7 years, event-free survival at one (primary end point) and 3 years was 88% (95% CI, 79 to 98) and 55% (95% CI, 40 to 71), while overall survival (OS) was 91% (95% CI, 82 to 99) and 73% (95% CI, 59 to 87), respectively. None of the patients died during 6 months after the start of induction. Most common adverse events having common toxicity criteria grade ≥3 during induction were leukocytopenia, neutropenia, thrombocytopenia, anemia, and elevated liver enzymes. One patient developed nonfatal veno-occlusive disease after induction II., Conclusion: Inotuzumab ozogamicin-based induction followed by age-adapted chemotherapy was well tolerated and resulted in high rates of remission and OS. These data provide a rationale for integrating inotuzumab ozogamicin into first-line regimens for older patients with B-ALL.

Background: This study evaluated the prognostic impact of age on patients presenting with ventricular tachyarrhythmias (VTA) and aborted cardiac arrest., Material and Methods: The present registry-based, monocentric cohort study included all consecutive patients presenting at the University Medical Center Mannheim (UMM) between 2002 and 2016 with ventricular tachycardia (VT), ventricular fibrillation (VF) and aborted cardiac arrest. Middle-aged (40-60 years old) were compared to older patients (> 60 years old). Furthermore, age was analyzed as a continuous variable. The primary endpoint was all-cause mortality at 2.5 years. The secondary endpoints were cardiac death at 24 h, all-cause mortality at index hospitalization, all-cause mortality after index hospitalization and the composite endpoint at 2.5 years of cardiac death at 24 h, recurrent VTA, and appropriate implantable cardioverter defibrillator (ICD) treatment., Results: A total of 2259 consecutive patients were included (28% middle-aged, 72% older). Older patients were more often associated with all-cause mortality at 2.5 years (27% vs. 50%; hazard ratio, HR = 2.137; 95% confidence interval, CI 1.809-2.523, p = 0.001) and the secondary endpoints. Even patient age as a continuous variable was independently associated with mortality at 2.5 years in all types of VTA. Adverse prognosis in older patients was demonstrated by multivariate Cox regression analyses and propensity score matching. Chronic kidney disease (CKD), systolic left ventricular dysfunction (LVEF) < 35%, cardiopulmonary resuscitation (CPR) and cardiogenic shock worsened the prognosis for both age groups, whereas acute myocardial infarction (STEMI/NSTEMI) and the presence of an ICD improved prognosis., Conclusion: The results of this study suggest that increasing age is associated with increased mortality in VTA patients. Compared to the middle-aged, older patients were associated with higher all-cause mortality at 2.5 years and the secondary endpoints., (© 2022. The Author(s).)

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Background: Electrical storm (ES) is a severe and life-threatening heart rhythm disorder. Age and male gender have been identified as independent risk factors for cardiovascular diseases. However, data regarding the prognostic impact of age and gender on ES patients is limited., Methods: The present study included retrospectively consecutive patients presenting with ES from 2002 to 2016. Patients 67 years old or older were compared to patients younger than 67, males were also compared to females. Receiver operating characteristic analyses were performed to find the optimum age cut-off value. The primary endpoint was all-cause mortality at 3 years. The secondary endpoints were in-hospital mortality, rehospitalization rates, ES recurrences, and major adverse cardiac events (MACE) at 3 years., Results: Eighty-seven ES patients with implantable cardioverter-defibrillators were included. Age ≥ 67 years was associated with increased all-cause mortality at 3 years (48% vs. 20%, hazard ratio = 3.046; 95% confidence interval 1.316-7.051; p = 0.008; log-rank p = 0.006). MACE, in-hospital mortality, rehospitalization rates, and ES recurrences were not affected by age. Even after multivariate adjustment, age ≥ 67 years was associated with increased long-term mortality at 3 years, besides left ventricular ejection fraction < 35%. In contrast, gender was not associated with primary and secondary endpoints., Conclusions: Patients 67 years old and older presenting with ES are associated with poor long-term prognosis. Increased long-term mortality was still evident after multivariate adjustment. In contrast, gender was not associated with primary and secondary endpoints.

Allogeneic hematopoietic stem cell transplantation (HCT) is standard treatment for adult high-risk (HR) acute lymphoblastic leukemia (ALL) and contributed to the overall improved outcome. We report a consecutive cohort of prospectively defined HR patients treated on German Multicenter Acute Lymphoblastic Leukemia trials 06/99-07/03 with similar induction/consolidation therapy and HCT in first remission. A total of 542 patients (15-55 years) with BCR-ABL-negative ALL were analyzed. Sixty-seven percent received HCT from matched unrelated donors (MUD) and 32% from matched sibling donors (MSD). The incidence of non-relapse mortality (NRM) was 20% at 5 years. NRM occurred after median 6.6 months; the leading cause (46%) was infection. NRM after MUD decreased from 39% in trial 06/99 to 16% in trial 07/03 (P < .00001). Patient age was the strongest predictor of NRM. The 5-year relapse incidence was 23% using MSD and 25% using MUD. Minimal residual disease (MRD) was the strongest predictor of relapse (45% for molecular failure versus 6% for molecular CR; P < .0001). The median follow-up was 67 months, and the 5-year survival rate was 58%. Age, subtype/high risk feature, MRD status, trial and acute GvHD were significant prognostic factors. We provide a large reference analysis with long follow-up confirming a similar outcome of MSD and MUD HCT and improved NRM for MUD HCT over years. MRD has a strong impact on relapse risk, whereas age was the strongest predictor of NRM. New adapted conditioning strategies should be considered for older patients combined with the goal to reduce the MRD level before stem cell transplantation., Competing Interests: Declaration of Competing Interest M.B. received personal fees from Incyte (advisory board) and Roche Pharma AG, financial support for reference diagnostics from Affimed and Regeneron, grants and personal fees from Amgen (advisory board, speakers bureau, travel support), and personal fees from Janssen (speakers bureau). G.K. received research funding from Celgene and Amgen, Lecture fees, advisory board fees and travel support from Celgene, Amgen, Pfizer, Jazz, Neovii, Takeda, Medac, Biotest, Eurocept, MSD, Roche, Iqone, Novartis, Gilead and Abbvie N.A received honoraria for lectures from Amgen; honoraria for advisory board from Gilead, MSD Sharp & Dohme GmbH, Pfizer, Amgen, Travel grant from Gilead, MSD Sharp & Dohme GmbH, Pfizer and Amgen. N.G. received speaker honoraria, travel support or advisory board fees from Amgen, Celgene, Gilead, Novartis, Pfizer, Jazz Pharmaceuticals, Incyte, Cellestia, Erytech and Morphosys and research support (institution) from Amgen, Pfizer, Novartis, Shire/Servier, Jazz Pharmaceuticals and Incyte., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR) like the third-generation TKI osimertinib have substantially improved the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring sensitizing EGFR mutations. However, there is a subset of patients that do not benefit from these therapies in terms of response rate or progression-free-survival (PFS). It has been shown that persistence of EGFR mutations in circulating tumor DNA (ctDNA) at weeks 3 and 6 after start of osimertinib predicts shorter PFS. These patients may benefit from additional chemotherapy. While combination therapies with older TKI have been demonstrated effective in improving outcome, they are associated with a significant increase in toxicity., Patients and Methods: PACE-LUNG is a multicenter, single-arm, investigator initiated, phase II trial conducted with the German national Network Genomic Medicine (nNGM). Patients with stage IIIB or IV NSCLC and exon 19 deletion or p.L858R EGFR mutation not amenable to curative treatment with persisting ctDNA after 3 to 4 weeks of first-line osimertinib monotherapy will receive additional chemotherapy (4 cycles of either cisplatin/pemetrexed or carboplatin/pemetrexed). Afterwards, osimertinib will be continued as standard of care until disease progression or intolerable toxicity. The primary endpoint is PFS. Secondary endpoints include overall survival, response rate, safety, and quality of life. Concomitant translational research will be performed to identify patterns of mutational evolution in ctDNA upon disease progression or ctDNA persistence. Enrollment started in December 2021., Discussion: The PACE-LUNG trial is designed to evaluate the efficacy and safety of a biomarker-driven strategy for therapy escalation in patients at high risk for early treatment failure. This approach aims not only to improve treatment outcomes, but also to limit the anticipated additional toxicity to high-risk patients., Trial Registration Number: 2019-004757-88 (EudraCT)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The Arabidopsis Information Resource (TAIR; http://arabidopsis.org) is a comprehensive web resource of Arabidopsis biology for plant scientists. TAIR curates and integrates information about genes, proteins, gene function, orthologs, gene expression, mutant phenotypes, biological materials such as clones and seed stocks, genetic markers, genetic and physical maps, genome organization, images of mutant plants, protein sub-cellular localizations, publications, and the research community. The various data types are extensively interconnected and can be accessed through a variety of web-based search and display tools. This article primarily focuses on some basic methods for searching, browsing, visualizing, and analyzing information about Arabidopsis genes and genomes. Additionally, we describe how members of the community can share data via JBrowse and the Generic Online Annotation Submission Tool (GOAT) in order to make their published research more accessible and visible. © 2022 Wiley Periodicals LLC. Basic Protocol 1: TAIR homepage, sitemap, and navigation Basic Protocol 2: Finding comprehensive information about Arabidopsis genes Basic Protocol 3: Using the Arabidopsis genome browser: JBrowse Basic Protocol 4: Using the Gene Ontology annotations for gene discovery and gene function analysis Basic Protocol 5: Using gene lists to download bulk datasets Basic Protocol 6: Using TAIR's analysis tools to find short sequences and motifs Basic Protocol 7: Using the TAIR generic online annotation tool (GOAT) to submit functional annotations for Arabidopsis (or any other species) genes Basic Protocol 8: Using PhyloGenes to visualize gene families and predict functions Basic Protocol 9: Using TAIR to browse Arabidopsis literature Basic Protocol 10: Using the synteny viewer to find and display syntenic regions from Arabidopsis and other plant species., (© 2022 Wiley Periodicals LLC.)

Background: he distribution and prognostic impact of coronary artery disease (CAD) in ES are still under debate., Methods: Consecutive ES patients with implantable cardioverter-defibrillator (ICD) were included retrospectively from 2002 to 2016. Three analyses were applied to characterize ES patients: (a) ES patients without CAD (non-CAD), (b) ES patients with CAD (CAD), and (c) diagnostic findings assessed by coronary angiography (CA) at the time of ES (immediate CA). CAD was compared with non-CAD ES patients, and progressive CAD was compared with stable CAD ES patients. The primary endpoint was all-cause mortality at 2.5 years. Secondary endpoints were the composite endpoint of first recurrent ventricular tachyarrhythmias and appropriate ICD therapies, and recurrence of ES (ES-R) at 2.5 years., Results: Within a total of 87 consecutive ES patients. CAD was present in more than two-thirds (67%). However, only 52% patients underwent immediate CA at the time of ES. Here, 84% had CAD, of which 39% revealed progressive CAD with the need of target vessel revascularization (TVR) or cardiac transplantation ( n = 1). At long-term follow-up, neither the presence (or absence) of CAD (41% vs. 34%; log rank P = 0.708) nor of progressive CAD (33% vs. 26%; log rank P = 0.372) was associated with all-cause mortality at 2.5 years, and further secondary endpoints including the composite of recurrent ventricular tachyarrhythmias plus appropriate ICD therapies, or ES-R., Conclusion: In ES patients, CAD was more common than non-CAD-related cardiac diseases, accompanied by an underinvestigated rate of CA despite increasing rates of progressive CAD. CAD had no prognostic impact in ES., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The study investigates the prognostic significance of beta-blocker (BB) dose in patients with ventricular tachyarrhythmias. Limited data regarding the prognostic impact of BB dose in ventricular tachyarrhythmias is available. A large retrospective registry was used including consecutive patients on BB treatment with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Discharge BB doses were grouped as > 0-12.5%, > 12.5-25%, > 25-50%, and > 50% according to doses used in randomized trials. The primary endpoint was all-cause mortality at three years. Secondary endpoints comprised of a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias and appropriate ICD therapies) and cardiac rehospitalization. Kaplan-Meier survival curves and multivariable Cox regression analyses were applied for statistics. A total of 1313 patients with BB were included; most patients were discharged with > 25-50% of BB target dose (59%). At three years, > 12.5-25% of BB target dose was associated with improved long-term mortality as compared to the > 0-12.5% group (HR = 0.489; 95% CI 0.297-0.806; p = 0.005), whereas higher BB doses did not improve survival (> 25-50%: HR = 0.849; p = 0.434; > 50%: HR = 0.735; p = 0.285). In contrast, the composite endpoint and risk of rehospitalization were not affected by BB target dose. In conclusion, > 12.5-25% of BB target dose is associated with best long-term survival among patients with ventricular tachyarrhythmias. In contrast, risk of the composite arrhythmic endpoint and risk of cardiac rehospitalization were not affected by BB dose., (© 2022. The Author(s).)

Limited data regarding the prognostic impact of ventricular tachyarrhythmias related to out-of-hospital (OHCA) compared to in-hospital cardiac arrest (IHCA) is available. A large retrospective single-center observational registry with all patients admitted due to ventricular tachyarrhythmias was used including all consecutive patients with ventricular tachycardia (VT) and fibrillation (VF) on admission from 2002 to 2016. Survivors discharged after OHCA were compared to those after IHCA using multivariable Cox regression models and propensity-score matching for evaluation of the primary endpoint of long-term all-cause mortality at 2.5 years. Secondary endpoints were all-cause mortality at 6 months and cardiac rehospitalization at 2.5 years. From 2.422 consecutive patients with ventricular tachyarrhythmias, a total of 524 patients survived cardiac arrest and were discharged from hospital (OHCA 62%; IHCA 38%). In about 50% of all cases, acute myocardial infarction was the underlying disease leading to ventricular tachyarrhythmias with consecutive aborted cardiac arrest. Survivors of IHCA were associated with increased long-term all-cause mortality compared to OHCA even after multivariable adjustment (28% vs. 16%; log rank p = 0.001; HR 1.623; 95% CI 1.002-2.629; p = 0.049) and after propensity-score matching (28% vs. 19%; log rank p = 0.045). Rates of cardiac rehospitalization rates at 2.5 years were equally distributed between OHCA and IHCA survivors. In patients presenting with ventricular tachyarrhythmias, survivors of IHCA were associated with increased risk for all-cause mortality at 2.5 years compared to OHCA survivors., (© 2021. The Author(s).)

Background: This study evaluates cardiac diseases and prognosis in young adults and adults presenting with ventricular tachyarrhythmias (VTA)., Methods: The present longitudinal, observational, registry-based, monocentric cohort study includes all consecutive patients 45 years old or younger presenting with VTA at admission from 2002 to 2016. Rates of coronary angiography, coronary artery disease (CAD) and need for percutaneous coronary intervention (PCI), cardiac diseases associated with VTA, and differences in long-term prognostic endpoints for young adults (20-34 years old) were analyzed and compared to those of adults (35-45 years old), for whom multivariable risk prediction models were developed. Kaplan-Meier analyses were performed according to age and type of VTA., Results: A total of 259 consecutive patients were included in the study (36% young adults and 64% adults). At admission, 38% of young adults had VTA due to CAD that required PCI. Furthermore, VTA in young adults was commonly idiopathic (27%), or had underlying channelopathies (18%), primary cardiomyopathies (13%) or acute myocardial infarction (AMI, 11%). In adults, VTA was mostly associated with AMI (28%), though the rate of idiopathy was still high (20%). A total 41% of all patients received cardiopulmonary resuscitation (CPR), for whom AMI (STEMI 17%, NSTEMI 24%) was most frequently observed. Irrespective of the type of VTA, all-cause mortality was similar for young adults and adults. In young adults, left ventricular ejection fraction (LVEF) < 35% (HR = 33.590) was associated with increased long-term all-cause mortality., Conclusion: Despite high rates of idiopathic ventricular tachyarrhythmias, CAD and AMI are common causes of VTA and CPR in adults 45 years old and younger. Young adults and adults had comparable survival at index hospitalization and after 2.5 years irrespective of the type of VTA. Clinical trial registration clinicaltrials.gov identifier: NCT02982473., (© 2022. The Author(s).)

Background: The study sought to assess the prognostic impact of chronic kidney disease (CKD) in patients with electrical storm (ES). ES represents a life-threatening heart rhythm disorder. In particular, CKD patients are at risk of suffering from ES. However, data regarding the prognostic impact of CKD on long-term mortality in ES patients is limited., Methods: All consecutive ES patients with an implantable cardioverter-defibrillator (ICD) were included retrospectively from 2002 to 2016. Patients with CKD (MDRD-GFR < 60 ml/min/1.73 m 2 ) were compared to patients without CKD. The primary endpoint was all-cause mortality at 3 years. Secondary endpoints were in-hospital mortality, cardiac rehospitalization, recurrences of electrical storm (ES-R), and major adverse cardiac events (MACE) at 3 years., Results: A total of 70 consecutive ES patients were included. CKD was present in 43% of ES patients with a median glomerular filtration rate (GFR) of 43.3 ml/min/1.73 m 2 . CKD was associated with increased all-cause mortality at 3 years (63% vs. 20%; p = 0.001; HR = 4.293; 95% CI 1.874-9.836; p = 0.001) and MACE (57% vs. 30%; p = 0.025; HR = 3.597; 95% CI 1.679-7.708; p = 0.001). In contrast, first cardiac rehospitalization (43% vs. 45%; log-rank p = 0.889) and ES-R (30% vs. 20%; log-rank p = 0.334) were not affected by CKD. Even after multivariable adjustment, CKD was still associated with increased long-term mortality (HR = 2.397; 95% CI 1.012-5.697; p = 0.047), as well as with the secondary endpoint MACE (HR = 2.520; 95% CI 1.109-5.727; p = 0.027)., Conclusions: In patients with ES, the presence of CKD was associated with increased long-term mortality and MACE., (© 2021. The Author(s).)

Introduction: The study sought to assess the effect of treatment with mineralocorticoid receptor antagonists (MRAs) on long-term prognosis of patients with systolic heart failure (HF) surviving index episodes of ventricular tachyarrhythmias., Methods: A large retrospective registry was used including consecutive HF patients with left ventricular ejection fraction <45% and index episodes of ventricular tachyarrhythmias from 2002 to 2015. The primary endpoint was all-cause mortality at 3 years and secondary endpoints were rehospitalization, as well as the composite endpoint consisting of recurrent ventricular tachyarrhythmias, sudden cardiac death and appropriate implantabe cardioverter defibrillator (ICD) therapies at 3 years., Results: 748 patients were included, 20% treated with MRA and 80% without. At 3 years, treatment with MRA was not associated with improved all-cause mortality (22% vs. 24%, log-rank p = 0.968; hazard ratio (HR) = 1.008; 95% CI 0.690-1.472; p = 0.968). Accordingly, risk of the composite endpoint (28% vs. 27%; HR = 1.131; 95% CI 0.806-1.589; p = 0.476) and first cardiac rehospitalization (24% vs. 22%; HR = 1.139; 95% CI 0.788-1.648; p = 0.489) were not affected by treatment with MRA., Conclusion: In patients with ventricular tachyarrhythmias, treatment with MRA was not associated with improved all-cause mortality at 3 years. The therapeutic effect of MRA treatment in patients with ventricular tachyarrhythmias needs to be reinvestigated within further randomized controlled trials., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Both acute myocardial infarction complicated by ventricular tachyarrhythmias (AMI-VTA) and electrical storm (ES) represent life-threatening clinical conditions. However, a direct comparison of both sub-groups regarding prognostic endpoints has never been investigated. All consecutive implantable cardioverter-defibrillator (ICD) recipients were included retrospectively from 2002 to 2016. Patients with ES apart from AMI (ES) were compared to patients with AMI accompanied by ventricular tachyarrhythmias (AMI-VTA). The primary endpoint was all-cause mortality at 3 years, secondary endpoints were in-hospital mortality, rehospitalization rates and major adverse cardiac event (MACE) at 3 years. A total of 198 consecutive ICD recipients were included (AMI-VTA: 56%; ST-segment elevation myocardial infarction (STEMI): 22%; non-ST-segment myocardial infarction (NSTEMI) 78%; ES: 44%). ES patients were older and had higher rates of severely reduced left ventricular ejection fraction (LVEF) < 35%. ES was associated with increased all-cause mortality at 3 years (37% vs. 19%; p = 0.001; hazard ratio [HR] = 2.242; 95% CI 2.291-3.894; p = 0.004) and with increased risk of first cardiac rehospitalization (44% vs. 12%; p = 0.001; HR = 4.694; 95% CI 2.498-8.823; p = 0.001). This worse prognosis of ES compared to AMI-VTA was still evident after multivariable adjustment (long-term all-cause mortality: HR = 2.504; 95% CI 1.093-5.739; p = 0.030; first cardiac rehospitalization: HR = 2.887; 95% CI 1.240-6.720; p = 0.014). In contrast, the rates of MACE (40% vs. 32%; p = 0.326) were comparable in both groups. At long-term follow-up of 3 years, ES was associated with higher rates of all-cause mortality and rehospitalization compared to patients with AMI-VTA., (© 2021. The Author(s).)

This study evaluates the prognostic impact of anemia in patients presenting with ventricular tachyarrhythmias. The present longitudinal, observational, registry-based, monocentric cohort study included retrospectively all consecutive patients presenting with ventricular tachyarrhythmias on admission from 2002 to 2016. Anemic patients (hemoglobin levels <12.0 g/dl) were compared with non-anemic patients (hemoglobin levels ≥12.0 g/dl). The primary endpoint was all-cause mortality at 2.5 years. Secondary endpoints were cardiac death at 24 hours, all-cause mortality at index hospitalization, and the composite endpoint of cardiac death at 24 hours, recurrent ventricular tachyarrhythmias, and appropriate ICD therapies at 2.5 years. A total of 2,184 consecutive patients were included, of whom 30% were anemic and 70% non-anemic. Anemia was associated with the primary endpoint of all-cause mortality at 2.5 years (65% vs 29%, p = 0.001; HR = 2.441; 95% CI 2.086 to 2.856), cardiac death at 24 hours (26% vs 11%, p = 0.001), all-cause mortality at index hospitalization (45% vs 20%, p = 0.001), and the composite endpoint (35% vs 27%, p = 0.001; HR = 2.923; 95% CI 2.564 to 4.366). After multivariable adjustment, anemia was no longer associated with the composite endpoint. Predictors of adverse prognosis for anemics were CKD (HR = 2.191), LVEF <35% (HR = 1.651), cardiogenic shock (HR = 1.591), CPR (HR = 1.460), male gender (HR = 1.379), and age (HR = 1.017). In conclusion, anemic patients presenting with ventricular tachyarrhythmias were associated with increased long-term mortality at 2.5 years but not with the composite arrhythmic endpoint at 2.5 years. Predictors of adverse prognosis at 2.5 years were CKD, LVEF <35%, cardiogenic shock, CPR, male gender, and age., Competing Interests: Disclosures The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Data regarding recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients according to atrial fibrillation is limited., Objective: To assess the prognostic impact of atrial fibrillation on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator recipients., Methods: A large retrospective registry was used, including all ICD recipients with episodes of ventricular tachycardia or fibrillation from 2002 to 2016. Patients with atrial fibrillation were compared to those without atrial fibrillation. The primary endpoint was first recurrence of ventricular tachyarrhythmias at 5 years. Secondary endpoints comprised recurrences of ICD-related therapies, first cardiac rehospitalization and all-cause mortality at 5 years. Cox regression, Kaplan-Meier and propensity score-matching analyses were applied., Results: A total of 592 consecutive ICD recipients were included (33% with atrial fibrillation). Atrial fibrillation was associated with reduced freedom from recurrent ventricular tachyarrhythmias (42% vs. 50%, log-rank P=0.004; hazard ratio 1.445, 95% confidence interval 1.124-1.858), mainly attributable to recurrent ventricular fibrillation in secondary-preventive ICD recipients. Accordingly, atrial fibrillation was associated with reduced freedom from first appropriate ICD therapies (31% vs. 42%, log-rank P=0.001; hazard ratio 1.598, 95% confidence interval 1.206-2.118). Notably, the primary endpoint of freedom from first episode of recurrent ventricular tachyarrhythmias was still reduced in those with atrial fibrillation compared to those without atrial fibrillation after propensity score matching. Regarding secondary endpoints, patients with atrial fibrillation still showed a trend towards reduced freedom from appropriate ICD therapies., Conclusions: Atrial fibrillation was associated with increased rates of recurrent ventricular tachyarrhythmias and appropriate device therapies in ICD recipients with ventricular tachyarrhythmias., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

This study sought to assess the prognostic impact of treatment with single beta-blocker (BB) compared to combined therapy with BB plus amiodarone (BB-AMIO) on recurrences of ventricular tachyarrhythmias in implantable cardioverter-defibrillator (ICD) recipients. A large retrospective registry was used including consecutive ICD recipients with index episodes of ventricular tachyarrhythmias from 2002 to 2016. Patients treated with BB were compared to patients treated with BB-AMIO. Kaplan-Meier and Cox regression analyses were applied for the evaluation of the primary end-point defined as first recurrences of ventricular tachyarrhythmias at five years. Secondary end-points comprised first appropriate ICD therapies, first cardiac rehospitalization and all-cause mortality at five years. Among 512 ICD recipients, 81% were treated with BB and 19% with BB-AMIO. BB and BB-AMIO were associated with comparable risk of first recurrences of ventricular tachyarrhythmias (46% vs. 43%; log rank P = .941; HR = 1.013; 95% CI 0.725-1.415; P = .941) and appropriate ICD therapies (35% vs. 37%; log rank P = .389; HR = 0.852; 95% CI 0.591-1.228; P = .390). BB was associated with decreased long-term all-cause mortality within an univariable analysis only (20% vs. 28%; log rank p = 0.023). In conclusion, BB and BB-AMIO were associated with comparable risks regarding recurrences of ventricular tachyarrhythmias at five years., (© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd).)

Objective: The study sought to assess the prognostic impact of treatment with mineralocorticoid receptor antagonists (MRA) on recurrences of ventricular tachyarrhythmias in implantable cardioverter-defibrillator (ICD) recipients with systolic heart failure (HF)., Background: Data regarding the outcome of patients with ventricular tachyarrhythmias treated with MRA is limited., Methods: A large retrospective registry was used including consecutive ICD recipients with systolic HF (i.e., left ventricular ejection fraction < 45%) and index episodes of ventricular tachyarrhythmias from 2002 to 2016. Patients treated with MRA were compared to patients without (non-MRA). Kaplan-Meier and multivariable Cox regression analyses were applied for the evaluation of the primary endpoint defined as first recurrence of ventricular tachyarrhythmias at five years. Secondary endpoints were appropriate ICD therapies, first cardiac rehospitalization, and all-cause mortality., Results: 366 ICD recipients with systolic HF were included, 20% treated with MRA (spironolactone: 65%; eplerenone: 35%) and 80% without. At five years, treatment with MRA was not associated with the primary endpoint of first recurrence of ventricular tachyarrhythmias [47% vs. 48%, log-rank p = 0.732; hazard ratio (HR) = 1.067; 95% confidence interval (CI) 0.736-1.546; p = 0.732]. Accordingly, risk of first appropriate ICD therapies, first cardiac rehospitalization, and all-cause mortality were not affected by the presence of MRA therapy. Finally, patients with spironolactone and eplerenone had comparable risk of first recurrences of ventricular tachyarrhythmias (50% vs. 45%; p = 0.255; HR = 2.263; 95% CI 0.495-10.341; p = 0.292)., Conclusion: Treatment with MRA was not associated with recurrences of ventricular tachyarrhythmias and ICD therapies at five years., (© 2020 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Background: Despite a few studies evaluating the prognostic impact of coronary chronic total occlusion (CTO) in implantable cardioverter defibrillator (ICD) recipients, the impact of CTO on different types of recurrences of ventricular tachyarrhythmias, as well as their predictors has not yet been investigated in CTO patients., Methods: A large retrospective registry was used including all consecutive patients with ventricular tachyarrhythmias undergoing coronary angiography at index from 2002 to 2016. Only ICD recipients with CTO were compared to patients without (non-CTO). Kaplan-Meier and Cox regression analyses were applied for the primary end point of first recurrence of ventricular tachyarrhythmias at 5 years. Secondary end points comprised of the different types of recurrences, first appropriate ICD therapy and all-cause mortality at 5 years., Results: From a total of 422 consecutive ICD recipients with ventricular tachyarrhythmias at index, at least one CTO was present in 25%. CTO was associated with the primary end point of first recurrence of ventricular tachyarrhythmias at 5 years (55% vs. 39%; log rank p = 0.001; HR = 1.665; 95% CI 1.221-2.271; p = 0.001), as well as increased risk of first appropriate ICD therapy (40% vs. 31%; log rank p = 0.039; HR = 1.454; 95% CI 1.016-2.079; p = 0.041) and all-cause mortality at 5 years (26% vs. 16%; log rank p = 0.011; HR = 1.797; 95% CI 1.133-2.850; p = 0.013). Less developed collaterals (i.e., either ipsi- or contralateral compared to bilateral) and a J-CTO score ≥ 3 were strongest predictors of recurrences in CTO patients at 5 years., Conclusion: A coronary CTO even in the presence of less developed collaterals and more complex CTO category is associated with increasing risk of recurrent ventricular tachyarrhythmias at 5 years in consecutive ICD recipients.

We aim to enable the accurate and efficient transfer of knowledge about gene function gained from Arabidopsis thaliana and other model organisms to other plant species. This knowledge transfer is frequently challenging in plants due to duplications of individual genes and whole genomes in plant lineages. Such duplications result in complex evolutionary relationships between related genes, which may have similar sequences but highly divergent functions. In such cases, functional inference requires more than a simple sequence similarity calculation. We have developed an online resource, PhyloGenes (phylogenes.org), that displays precomputed phylogenetic trees for plant gene families along with experimentally validated function information for individual genes within the families. A total of 40 plant genomes and 10 non-plant model organisms are represented in over 8,000 gene families. Evolutionary events such as speciation and duplication are clearly labeled on gene trees to distinguish orthologs from paralogs. Nearly 6,000 families have at least one member with an experimentally supported annotation to a Gene Ontology (GO) molecular function or biological process term. By displaying experimentally validated gene functions associated to individual genes within a tree, PhyloGenes enables functional inference for genes of uncharacterized function, based on their evolutionary relationships to experimentally studied genes, in a visually traceable manner. For the many families containing genes that have evolved to perform different functions, PhyloGenes facilitates the use of evolutionary history to determine the most likely function of genes that have not been experimentally characterized. Future work will enrich the resource by incorporating additional gene function datasets such as plant gene expression atlas data., (© 2020 The Authors. Plant Direct published by American Society of Plant Biologists, Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: The study sought to assess the prognostic impact of potassium levels (K) in patients with ventricular tachyarrhythmias., Methods: A large retrospective registry was used including all consecutive patients presenting with ventricular tachyarrhythmias on admission from 2002 to 2016. Patients with hypokalemia (i.e., K < 3.3 mmol/L), normokalemia (i.e., K 3.3-4.5 mmol/L), and hyperkalemia (i.e., K > 4.5 mmol/L) were compared applying multi-variable Cox regression models and propensity-score matching for evaluation of the primary endpoint of all-cause mortality at 3 years. Secondary endpoints were early cardiac death at 24 h, in-hospital death, death at 30 days, as well as the composite endpoint of early cardiac death at 24 h, recurrences of ventricular tachyarrhythmias, and appropriate ICD therapies at 3 years., Results: In 1990 consecutive patients with ventricular tachyarrhythmias, 63% of the patients presented with normokalemia, 30% with hyperkalemia, and 7% with hypokalemia. After propensity matching, both hypokalemic (HR = 1.545; 95% CI 0.970-2.459; p = 0.067) and hyperkalemic patients (HR = 1.371; 95% CI 1.094-1.718; p = 0.006) were associated with the primary endpoint of all-cause mortality at 3 years compared to normokalemic patients. Hyperkalemia was associated with even worse prognosis directly compared to hypokalemia (HR = 1.496; 95% CI 1.002-2.233; p = 0.049). In contrast, potassium measurements were not associated with the composite endpoint at 3 years., Conclusion: In patients presenting with ventricular tachyarrhythmias, normokalemia was associated with best short- and long-term survival, whereas hyperkalemia and hypokalemia were associated with increased mortality at 30 days and at 3 years.

Objective: The study sought to assess the impact of ischemic (ICMP) compared to non-ischemic cardiomyopathy (NICMP) on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients., Background: Data comparing recurrences of ventricular tachyarrhythmias in ICD recipients with ischemic or non-ischemic cardiomyopathy is limited., Methods: A large retrospective registry was used including all consecutive ICD recipients with first episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2016. Patients with ICMP were compared to patients with NICMP. The primary prognostic endpoint was first recurrences of ventricular tachyarrhythmias at one year. Secondary endpoints comprised ICD-related therapies, rehospitalization and all-cause mortality at one year. Statistics Kaplan-Meier survival and multivariable Cox regression analyses., Results: A total of 387 consecutive ICD recipients were included retrospectively (ICMP: 82%, NICMP: 18%). At one year of follow-up, freedom from first recurrences of ventricular tachyarrhythmias was lower in NICMP (81% vs. 71%, log-rank p = 0.063; HR = 1.760; 95% CI 0.985-3.002; p = 0.080), mainly attributed to higher rates of sustained VT (20% versus 12%, p = 0.054). Accordingly, freedom from first appropriate device therapies was lower in NICMP (74% vs. 85%, log rank p = 0.004; HR = 1.951; 95% CI 1.121-3.397; p = 0.028), especially in patients with sustained VT or VF at index. Both groups revealed comparable rates of rehospitalization and all-cause mortality at one year., Conclusion: NICMP was associated with higher rates of recurrent ventricular tachyarrhythmias and appropriate ICD therapies compared to ICMP at one year of follow-up, whereas rates of rehospitalization and all-cause mortality were comparable., Condensed Abstract: This study retrospectively compared the impact of cardiomyopathy types (ICMP versus NICMP) on recurrences of ventricular tachyarrhythmias in 387 ICD recipients. Freedom from first episodes of ventricular tachyarrhythmias and first appropriate device therapies were lower in patients with NICMP compared to ICMP., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Only few data evaluating the prognostic impact of blood-derived potassium levels (K) on arrhythmic endpoints in patients with implantable cardioverter-defibrillators (ICD) is available. Therefore, this study evaluates the prognostic impact of potassium levels on recurrences of ventricular tachyarrhythmias in consecutive ICD recipients., Methods: A large retrospective registry was used including all consecutive patients presenting with ventricular tachyarrhythmias on admission from 2002 to 2016 at one institution. Patients were divided into three subgroups: hypokalemia (i.e., K < 3.3 mmol/L), normokalemia (i.e., K 3.3 - 4.5 mmol/L), and hyperkalemia (i.e., K > 4.5 mmol/L). Kaplan-Meier and Cox regression analyses were applied for the evaluation of the primary endpoint of first recurrences of ventricular tachyarrhythmias at one year. Secondary endpoints comprised of first appropriate ICD therapy, first cardiac rehospitalization, and all-cause mortality at one year., Results: Five hundred and thirty ICD recipients with a median potassium level of 4.23 mmol/L were included (67%: normokalemia, 27%: hyperkalemia, and 6%: hypokalemia). Whereas hyperkalemia was not associated with increasing risk of recurrent ventricular tachyarrhythmias, hypokalemia was associated with decreasing freedom from recurrent ventricular tachyarrhythmias (HR = 2.135; 95% CI 1.158 - 3.937; p = 0.015), even after mul-tivariable adjustment (HR = 2.577; 95% CI 1.236 - 5.372; p = 0.012). Higher risk of recurrences was especially attributed to higher rates of electrical storm in the presence of hypokalemia (15% vs. 3 - 4%). Negative impact of hypokalemia was mainly attributed to secondary preventive ICD (HR = 2.637; 95% CI 1.325 - 5.248; p = 0.006). Moreover, hypokalemia was associated with increasing risk of appropriate ICD therapies (HR = 1.920; 95% CI 0.912 - 4.042; statistical trend: p = 0.086), which was still demonstrated after multivariable adjustment. In contrast, risk of first cardiac rehospitalization and all-cause mortality were not affected by potassium levels., Conclusions: In consecutive ICD recipients with ventricular tachyarrhythmias at index, hypokalemia - but not hyperkalemia - was associated with increasing risk of recurrent ventricular tachyarrhythmias and appropriate ICD therapies.

Aims: This study sought to assess the prognostic impact of coronary chronic total occlusions (CTO) in patients presenting with ventricular tachyarrhythmias on admission., Methods and Results: A large retrospective registry was used, including all consecutive patients presenting with ventricular tachyarrhythmias on admission and undergoing coronary angiography from 2002 to 2016. Patients with a CTO were compared with all other patients (non-CTO) for prognostic outcomes. Statistics comprised Kaplan-Meier and Cox regression analyses. Within a total of 1,461 consecutive patients included with ventricular tachyarrhythmias on admission, a CTO was present in 20%. At midterm follow-up of 18 months, the primary endpoint all-cause mortality had occurred in 40% of CTO patients compared to 27% of non-CTO patients (HR 1.563, 95% CI: 1.263-1.934; p=0.001). The rates of secondary endpoints were higher for in-hospital all-cause mortality at index (29% versus 20%, log-rank p=0.027) and the composite endpoint of cardiac death at 24 hours, recurrent ventricular tachyarrhythmias and appropriate ICD therapies at midterm follow-up (28% versus 20%, log-rank p=0.005). Mortality rates were highest in CTO patients with stable coronary artery disease (CAD), acute myocardial infarction and in patients surviving index hospitalisation., Conclusions: In patients presenting with ventricular tachyarrhythmias on admission, the presence of a coronary CTO is independently associated with an increase of midterm all-cause mortality, in-hospital all-cause mortality and the composite endpoint of early cardiac death, recurrent ventricular tachyarrhythmias and appropriate ICD therapies.

Background: Data regarding the outcome of patients with ventricular tachyarrhythmias related to arterial hypertension (AHT) and smoking is limited. The study sought to assess the prognostic impact of AHT and smoking on survival in patients presenting with ventricular tachyarrhythmias., Methods: All consecutive patients surviving ventricular tachycardia (VT) and ventricular fibrillation (VF) upon admission to the University Medical Center Mannheim (UMM), Germany from 2002 to 2016 were included and stratified according to AHT and smoking by propensity score matching. The primary prognostic endpoint was all-cause mortality at 30 months., Results: A total of 988 AHT-matched patients (494 each, with and without AHT) and a total of 872 smoking-matched patients (436 each, with and without smoking) were included. The rates of VT and VF were similar in both groups (VT: AHT 60% vs. no AHT 60%; smokers 61% vs. non-smokers 62%; VF: AHT 35% vs. no AHT 38%; smokers 39% vs. non-smokers 38%). Neither AHT nor smoking were associated with the primary endpoint of long-term all-cause mortality at 30 months (long-term mortality rates: AHT/no AHT, 26% vs. 28%; log-rank p = 0.525; smoking/non-smoking, 22% vs. 25%; log-rank p = 0.683)., Conclusions: Paradoxically, neither AHT nor smoking were associated with differences of long-term all-cause mortality in patients presenting with ventricular tachyarrhythmias.

Objective: This study evaluates the impact of left ventricular ejection fraction (LVEF) on recurrences of ventricular tachyarrhythmias in recipients of implantable cardioverter defibrillator (ICD)., Background: Data regarding recurrences of ventricular tachyarrhythmias in ICD recipients according to LVEF is limited., Methods: A large retrospective registry was used, including all consecutive ICD recipients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2016. Patients with LVEF <35% were compared to patients with LVEF ≥35%. The primary end point was first recurrences of ventricular tachyarrhythmias at 5 years. Secondary end points were ICD-related therapies, rehospitalization, and all-cause mortality at 5 years. Cox regression, Kaplan Meier, and propensity score matching analyses were applied., Results: A total of 528 consecutive ICD recipients were included (51% with LVEF ≥35% and 49% with LVEF <35%). LVEF <35% was associated with reduced freedom from recurrent ventricular tachyarrhythmias (40 vs. 49%, log rank p = 0.014; hazard ratio [HR] = 1.381; 95% confidence interval [CI] 1.066-1.788; p = 0.034), mainly attributed to recurrent sustained VT in primary preventive ICD recipients. Accordingly, LVEF <35% was associated with reduced freedom from first appropriate ICD therapies (28 vs. 41%, log rank p = 0.001; HR = 1.810; 95% CI 1.185-2.766; p = 0.001). Finally, LVEF <35% was associated with a higher rate of rehospitalization (23 vs. 34%; p = 0.005) and all-cause mortality at 5 years (13 vs. 29%; p = 0.001)., Conclusion: LVEF <35% was associated with reduced freedom from recurrent ventricular tachyarrhythmias, appropriate device therapies, rehospitalization and all-cause mortality secondary to index ventricular tachyarrhythmias., (© 2020 S. Karger AG, Basel.)

The study sought to assess the impact of chronic kidney disease (CKD) on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients. Data regarding the outcome of patients with CKD in ICD recipients is limited. A large retrospective registry was used including consecutive ICD recipients surviving episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2016. CKD patients were compared to non-CKD patients. The primary endpoint was the first recurrence of ventricular tachyarrhythmias at 5 years. Secondary endpoints were ICD-related therapies, rehospitalization and all-cause mortality at 5 years. Kaplan-Meier, multivariable Cox regression and propensity score matching were applied. A total of 585 consecutive patients were included (non-CKD: 57%, CKD: 43%). CKD had higher rates of the primary endpoint of recurrent ventricular tachyarrhythmias compared to non-CKD patients (50% vs. 40%; log rank p = 0.008; HR = 1.398; 95% CI 1.087-1.770; p = 0.009), which was irrespective of a primary or secondary preventive ICD and mainly attributed to recurrent VF (11% vs. 5%; p = 0.007) and electrical storm (ES) (10% vs. 5%; p = 0.010). Accordingly, CKD patients had higher rates of the secondary endpoint of appropriate ICD therapies (41% vs. 30%; log rank p = 0.002; HR = 1.532; 95% CI 1.163-2.018; p = 0.002), mainly attributed to appropriate ICD shocks (19% vs. 11%; p = 0.005). After multivariable Cox regression CKD was associated with a 1.4-fold higher risk of appropriate device therapies (HR = 1.353; 95% CI 1.001-1.825; p = 0.049), but not with first recurrence of ventricular tachyarrhythmias (p = 0.177). Irrespective of propensity score matching, CKD was associated with increasing all-cause mortality at 5 years (p = 0.001). The presence of CKD is associated with increased rates of recurrent ventricular tachyarrhythmias, appropriate device therapies, mainly attributed to appropriate shock, and all-cause mortality in ICD recipients at 5 years.