The Impact of Timing of Fixed Dose Triple Antihypertensive Combinations on Ambulatory Blood Pressure Monitoring Parameters.

INTRODUCTION: Re-establishing "dipping" physiology significantly reduces cardiovascular events. The aim was to investigate the effect of timing of fixed dose triple antihypertensive combinations on blood pressure (BP) control. METHODS: One hundred sixteen consecutive patients (62.7 ± 10.7 years, 38 men) with grade II hypertension were randomized into four groups. Group 1 and Group 2 patients were given angiotensin converting enzyme inhibitor-based triple antihypertensive pills to be taken in the morning or evening, respectively while Group 3 and Group 4 patients were given angiotensin receptor blocker (ARB) based triple antihypertensive pills to be taken in the morning or evening, respectively. All patients underwent 24-h ambulatory BP monitoring 1 month after the initiation of treatment. RESULTS: There were not any significant differences in the characteristics, BP values and loads among groups. All patients in each group had good BP control. Dipping pattern in systolic BP was observed significantly less in Group 3 patients taking ARB in the morning (3 patients) compared to other groups (12 patients) in each group, [P = .025]. Similarly, dipping pattern in diastolic BP was observed significantly less in Group 3 patients (4 patients) compared to others (13 patients) in Group 1 and 15 patients in Group 2 and Group 4, [P = .008]. Nondipping pattern was significantly associated with taking ARB in the morning, even when adjusted by age, sex, and other comorbidities. CONCLUSION: Fixed dose triple antihypertensive drug combinations enable good BP control regardless of the timing of drug while ARB-based ones may be taken in the evening to ensure dipping physiology.

G4Boost: a machine learning-based tool for quadruplex identification and stability prediction.

BACKGROUND: G-quadruplexes (G4s), formed within guanine-rich nucleic acids, are secondary structures involved in important biological processes. Although every G4 motif has the potential to form a stable G4 structure, not every G4 motif would, and accurate energy-based methods are needed to assess their structural stability. Here, we present a decision tree-based prediction tool, G4Boost, to identify G4 motifs and predict their secondary structure folding probability and thermodynamic stability based on their sequences, nucleotide compositions, and estimated structural topologies. RESULTS: G4Boost predicted the quadruplex folding state with an accuracy greater then 93% and an F1-score of 0.96, and the folding energy with an RMSE of 4.28 and R2 of 0.95 only by the means of sequence intrinsic feature. G4Boost was successfully applied and validated to predict the stability of experimentally-determined G4 structures, including for plants and humans. CONCLUSION: G4Boost outperformed the three machine-learning based prediction tools, DeepG4, Quadron, and G4RNA Screener, in terms of both accuracy and F1-score, and can be highly useful for G4 prediction to understand gene regulation across species including plants and humans.

Co-expression pan-network reveals genes involved in complex traits within maize pan-genome.

BACKGROUND: With the advances in the high throughput next generation sequencing technologies, genome-wide association studies (GWAS) have identified a large set of variants associated with complex phenotypic traits at a very fine scale. Despite the progress in GWAS, identification of genotype-phenotype relationship remains challenging in maize due to its nature with dozens of variants controlling the same trait. As the causal variations results in the change in expression, gene expression analyses carry a pivotal role in unraveling the transcriptional regulatory mechanisms behind the phenotypes. RESULTS: To address these challenges, we incorporated the gene expression and GWAS-driven traits to extend the knowledge of genotype-phenotype relationships and transcriptional regulatory mechanisms behind the phenotypes. We constructed a large collection of gene co-expression networks and identified more than 2 million co-expressing gene pairs in the GWAS-driven pan-network which contains all the gene-pairs in individual genomes of the nested association mapping (NAM) population. We defined four sub-categories for the pan-network: (1) core-network contains the highest represented ~ 1% of the gene-pairs, (2) near-core network contains the next highest represented 1-5% of the gene-pairs, (3) private-network contains ~ 50% of the gene pairs that are unique to individual genomes, and (4) the dispensable-network contains the remaining 50-95% of the gene-pairs in the maize pan-genome. Strikingly, the private-network contained almost all the genes in the pan-network but lacked half of the interactions. We performed gene ontology (GO) enrichment analysis for the pan-, core-, and private- networks and compared the contributions of variants overlapping with genes and promoters to the GWAS-driven pan-network. CONCLUSIONS: Gene co-expression networks revealed meaningful information about groups of co-regulated genes that play a central role in regulatory processes. Pan-network approach enabled us to visualize the global view of the gene regulatory network for the studied system that could not be well inferred by the core-network alone.

PrevAleNce and Associated factors of inappropriaTe dosing of direct Oral anticoaguLants In pAtients with Atrial Fibrillation: the ANATOLIA-AF Study.

PURPOSE: Inappropriate dosing of direct oral anticoagulants is associated with an increased risk of stroke, systemic embolism, major bleeding, cardiovascular hospitalization, and death in patients with atrial fibrillation. The main goal of the study was to determine the prevalence and associated factors of inappropriate dosing of direct oral anticoagulants in real-life settings. METHODS: This study was a multicenter, cross-sectional, observational study that included 2004 patients with atrial fibrillation. The study population was recruited from 41 cardiology outpatient clinics between January and May 2021. The main criteria for inappropriate direct oral anticoagulant dosing were defined according to the recommendations of the European Heart Rhythm Association. RESULTS: The median age of the study population was 72 years and 58% were women. Nine-hundred and eighty-seven patients were prescribed rivaroxaban, 658 apixaban, 239 edoxaban, and 120 dabigatran. A total of 498 patients (24.9%) did not receive the appropriate dose of direct oral anticoagulants. In a logistic regression model, advanced age, presence of chronic kidney disease and permanent atrial fibrillation, prescription of reduced doses of direct oral anticoagulants or edoxaban treatment, concomitant use of amiodarone treatment, and non-use of statin treatment were significantly associated with potentially inappropriate dosing of direct oral anticoagulants. CONCLUSION: The study demonstrated that the prevalence of inappropriate direct oral anticoagulant dosing according to the European Heart Rhythm Association recommendations was 24.9% in patients with atrial fibrillation. Several demographic and clinical factors were associated with the inappropriate prescription of direct oral anticoagulants.

FINDER: an automated software package to annotate eukaryotic genes from RNA-Seq data and associated protein sequences.

BACKGROUND: Gene annotation in eukaryotes is a non-trivial task that requires meticulous analysis of accumulated transcript data. Challenges include transcriptionally active regions of the genome that contain overlapping genes, genes that produce numerous transcripts, transposable elements and numerous diverse sequence repeats. Currently available gene annotation software applications depend on pre-constructed full-length gene sequence assemblies which are not guaranteed to be error-free. The origins of these sequences are often uncertain, making it difficult to identify and rectify errors in them. This hinders the creation of an accurate and holistic representation of the transcriptomic landscape across multiple tissue types and experimental conditions. Therefore, to gauge the extent of diversity in gene structures, a comprehensive analysis of genome-wide expression data is imperative. RESULTS: We present FINDER, a fully automated computational tool that optimizes the entire process of annotating genes and transcript structures. Unlike current state-of-the-art pipelines, FINDER automates the RNA-Seq pre-processing step by working directly with raw sequence reads and optimizes gene prediction from BRAKER2 by supplementing these reads with associated proteins. The FINDER pipeline (1) reports transcripts and recognizes genes that are expressed under specific conditions, (2) generates all possible alternatively spliced transcripts from expressed RNA-Seq data, (3) analyzes read coverage patterns to modify existing transcript models and create new ones, and (4) scores genes as high- or low-confidence based on the available evidence across multiple datasets. We demonstrate the ability of FINDER to automatically annotate a diverse pool of genomes from eight species. CONCLUSIONS: FINDER takes a completely automated approach to annotate genes directly from raw expression data. It is capable of processing eukaryotic genomes of all sizes and requires no manual supervision-ideal for bench researchers with limited experience in handling computational tools.

LncMachine: a machine learning algorithm for long noncoding RNA annotation in plants.

Following the elucidation of the critical roles they play in numerous important biological processes, long noncoding RNAs (lncRNAs) have gained vast attention in recent years. Manual annotation of lncRNAs is restricted by known gene annotations and is prone to false prediction due to the incompleteness of available data. However, with the advent of high-throughput sequencing technologies, a magnitude of high-quality data has become available for annotation, especially for plant species such as wheat. Here, we compared prediction accuracies of several machine learning algorithms using a 10-fold cross-validation. This study includes a comprehensive feature selection step to refine irrelevant and repeated features. We present a crop-specific, alignment-free coding potential prediction tool, LncMachine, that performs at higher prediction accuracies than the currently available popular tools (CPC2, CPAT, and CNIT) when used with the Random Forest algorithm. Further, LncMachine with Random Forest performed well on human and mouse data, with an average accuracy of 92.67%. LncMachine only requires either a FASTA file or a TAB separated CSV file containing features as input files. LncMachine can deploy several user-provided algorithms in real time and therefore be effortlessly applied to a wide range of studies.

JBrowse Connect: A server API to connect JBrowse instances and users.

We describe JBrowse Connect, an optional expansion to the JBrowse genome browser, targeted at developers. JBrowse Connect allows live messaging, notifications for new annotation tracks, heavy-duty analyses initiated by the user from within the browser, and other dynamic features. We present example applications of JBrowse Connect that allow users 1) to specify and execute BLAST searches by either running on the same host as the webserver, with a self-contained BLAST module leveraging NCBI Blast+ commands, or via a managed Galaxy instance that can optionally run on a different host, and 2) to run the primer design service Primer3. JBrowse Connect allows users to track job progress and view results in the context of the browser. The software is available under a choice of open source licenses including LGPL and the Artistic License.

MaizeGDB 2018: the maize multi-genome genetics and genomics database.

Since its 2015 update, MaizeGDB, the Maize Genetics and Genomics database, has expanded to support the sequenced genomes of many maize inbred lines in addition to the B73 reference genome assembly. Curation and development efforts have targeted high quality datasets and tools to support maize trait analysis, germplasm analysis, genetic studies, and breeding. MaizeGDB hosts a wide range of data including recent support of new data types including genome metadata, RNA-seq, proteomics, synteny, and large-scale diversity. To improve access and visualization of data types several new tools have been implemented to: access large-scale maize diversity data (SNPversity), download and compare gene expression data (qTeller), visualize pedigree data (Pedigree Viewer), link genes with phenotype images (MaizeDIG), and enable flexible user-specified queries to the MaizeGDB database (MaizeMine). MaizeGDB also continues to be the community hub for maize research, coordinating activities and providing technical support to the maize research community. Here we report the changes MaizeGDB has made within the last three years to keep pace with recent software and research advances, as well as the pan-genomic landscape that cheaper and better sequencing technologies have made possible. MaizeGDB is accessible online at https://www.maizegdb.org.

Gender-related clinical and management differences in patients with chronic heart failure with reduced ejection fraction.

AIM: Gender-related differences have been described in the clinical characteristics and management of patients with chronic heart failure with reduced ejection fraction (HFrEF). However, published data are conflictive in this regard. METHODS: We investigated differences in clinical and management variables between male and female patients from the ATA study, a prospective, multicentre, observational study that included 1462 outpatients with chronic HFrEF between January and June 2019. RESULTS: Study population was predominantly male (70.1%). In comparison to men, women with chronic HFrEF were older (66 ± 11 years vs 69 ± 12 years, P < .001), suffered more hospitalisations and presented more frequently with NYHA class III or IV symptoms. Ischaemic heart disease was more frequent in men, whereas anaemia, thyroid disease and depression were more frequent in women. No difference was seen between genders in the use rate of renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, or ivabradine, or in the proportion of patients achieving target doses of these drugs. Regarding device therapies, men were more often treated with an implantable cardioverter-defibrillator (ICD) and women received more cardiac resynchronisation therapy. CONCLUSION: In summary, although management seemed to be equivalent between genders, women tended to present with more symptoms, require hospitalisation more frequently and have different comorbidities than men. These results highlight the importance of gender-related differences in HFrEF and call for further research to clarify the causes of these disparities. Gender-specific recommendations should be included in future guidelines in HFrEF.

Multiple Variant Calling Pipelines in Wheat Whole Exome Sequencing.

The highly challenging hexaploid wheat (Triticum aestivum) genome is becoming ever more accessible due to the continued development of multiple reference genomes, a factor which aids in the plight to better understand variation in important traits. Although the process of variant calling is relatively straightforward, selection of the best combination of the computational tools for read alignment and variant calling stages of the analysis and efficient filtering of the false variant calls are not always easy tasks. Previous studies have analyzed the impact of methods on the quality metrics in diploid organisms. Given that variant identification in wheat largely relies on accurate mining of exome data, there is a critical need to better understand how different methods affect the analysis of whole exome sequencing (WES) data in polyploid species. This study aims to address this by performing whole exome sequencing of 48 wheat cultivars and assessing the performance of various variant calling pipelines at their suggested settings. The results show that all the pipelines require filtering to eliminate false-positive calls. The high consensus among the reference SNPs called by the best-performing pipelines suggests that filtering provides accurate and reproducible results. This study also provides detailed comparisons for high sensitivity and precision at individual and population levels for the raw and filtered SNP calls.

Tissue-specific gene expression and protein abundance patterns are associated with fractionation bias in maize.

BACKGROUND: Maize experienced a whole-genome duplication event approximately 5 to 12 million years ago. Because this event occurred after speciation from sorghum, the pre-duplication subgenomes can be partially reconstructed by mapping syntenic regions to the sorghum chromosomes. During evolution, maize has had uneven gene loss between each ancient subgenome. Fractionation and divergence between these genomes continue today, constantly changing genetic make-up and phenotypes and influencing agronomic traits. RESULTS: Here we regenerate the subgenome reconstructions for the most recent maize reference genome assembly. Based on both expression and abundance data for homeologous gene pairs across multiple tissues, we observed functional divergence of genes across subgenomes. Although the genes in the larger maize subgenome are often expressing more highly than their homeologs in the smaller subgenome, we observed cases where homeolog expression dominance switches in different tissues. We demonstrate for the first time that protein abundances are higher in the larger subgenome, but they also show tissue-specific dominance, a pattern similar to RNA expression dominance. We also find that pollen expression is uniquely decoupled from protein abundance. CONCLUSION: Our study shows that the larger subgenome has a greater range of functional assignments and that there is a relative lack of overlap between the subgenomes in terms of gene functions than would be suggested by similar patterns of gene expression and protein abundance. Our study also revealed that some reactions are catalyzed uniquely by the larger and smaller subgenomes. The tissue-specific, nonequivalent expression-level dominance pattern observed here implies a change in regulatory control which favors differentiated selective pressure on the retained duplicates leading to eventual change in gene functions.

PedigreeNet: a web-based pedigree viewer for biological databases.

MOTIVATION: Plant breeding aims to improve current germplasm that can tolerate a wide range of biotic and abiotic stresses. To accomplish this goal, breeders rely on developing a deeper understanding of genetic makeup and relationships between plant varieties to make informed plant selections. Although rapid advances in genotyping technology generated a large amount of data for breeders, tools that facilitate pedigree analysis and visualization are scant, leaving breeders to use classical, but inherently limited, hierarchical pedigree diagrams for a handful of plant varieties. To answer this need, we developed a simple web-based tool that can be easily implemented at biological databases, called PedigreeNet, to create and visualize customizable pedigree relationships in a network context, displaying pre- and user-uploaded data. RESULTS: As a proof-of-concept, we implemented PedigreeNet at the maize model organism database, MaizeGDB. The PedigreeNet viewer at MaizeGDB has a dynamically-generated pedigree network of 4706 maize lines and 5487 relationships that are currently available as both a stand-alone web-based tool and integrated directly on the MaizeGDB Stock Pages. The tool allows the user to apply a number of filters, select or upload their own breeding relationships, center a pedigree network on a plant variety, identify the common ancestor between two varieties, and display the shortest path(s) between two varieties on the pedigree network. The PedigreeNet code layer is written as a JavaScript wrapper around Cytoscape Web. PedigreeNet fills a great need for breeders to have access to an online tool to represent and visually customize pedigree relationships. AVAILABILITY AND IMPLEMENTATION: PedigreeNet is accessible at https://www.maizegdb.org/breeders_toolbox. The open source code is publically and freely available at GitHub: https://github.com/Maize-Genetics-and-Genomics-Database/PedigreeNet. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MaizeGDB update: new tools, data and interface for the maize model organism database.

MaizeGDB is a highly curated, community-oriented database and informatics service to researchers focused on the crop plant and model organism Zea mays ssp. mays. Although some form of the maize community database has existed over the last 25 years, there have only been two major releases. In 1991, the original maize genetics database MaizeDB was created. In 2003, the combined contents of MaizeDB and the sequence data from ZmDB were made accessible as a single resource named MaizeGDB. Over the next decade, MaizeGDB became more sequence driven while still maintaining traditional maize genetics datasets. This enabled the project to meet the continued growing and evolving needs of the maize research community, yet the interface and underlying infrastructure remained unchanged. In 2015, the MaizeGDB team completed a multi-year effort to update the MaizeGDB resource by reorganizing existing data, upgrading hardware and infrastructure, creating new tools, incorporating new data types (including diversity data, expression data, gene models, and metabolic pathways), and developing and deploying a modern interface. In addition to coordinating a data resource, the MaizeGDB team coordinates activities and provides technical support to the maize research community. MaizeGDB is accessible online at http://www.maizegdb.org.

Right Ventricular Dysfunction Complicates Time in Therapeutic Range in Heart Failure Patients Receiving Warfarin.

AIM: We aimed to evaluate the effect of echocardiographically demonstrated right ventricular dysfunction (RVD) on time in therapeutic range (TTR) in heart failure (HF) patients receiving warfarin therapy. METHODS: A total of 893 consecutive HF patients were included and classified into 4 different subgroups: HF with preserved ejection fraction (HFpEF) without RVD (n = 373), HF with reduced EF (HFrEF) without RVD (n = 215), HFpEF with RVD (n = 106) and HFrEF with RVD (n = 199). Groups were compared according to baseline, demographic and clinical data and the characteristics of warfarin therapy. RESULTS: Presence of RVD yielded lower median TTR values both in HFpEF and HFrEF patients. RVD, current smoking, New York Heart Association functional class III/IV, hypertension, diabetes mellitus, pulmonary disease, prior transient ischemic attack or stroke, chronic kidney disease (CKD) stage 4/5 and CKD stage 3 were found to be independent predictors of poor anticoagulation control in multivariate logistic regression analysis. CONCLUSIONS: The present study demonstrated that presence of RVD in HF increases the risk for poor anticoagulation.

One-year results of primary stenting for TASC II D lesions of the superficial femoral and popliteal arteries.

Objective This study aimed to evaluate the safety and the efficacy of primary stenting to treat Trans-Atlantic Inter-Society Consensus II (TASC) D femoropopliteal lesions. Background Advances in wire, balloon and stent design have been reported to improve the durability of stenting of longer femoropopliteal lesions. Methods A total of 57 limbs of 53 patients with Rutherford stage 3 to 6 due to TASC D femoropopliteal lesions were treated with a self-expanding nitinol stent in a prospective, single-centre, observational study. End points of interest included primary and secondary patency, target lesion revascularization, in-stent restenosis, major adverse cardiovascular events, Rutherford class improvement and change in walking capacity at 1 year. Results A total of 53 patients (57 lesions) were treated with a self-expanding nitinol stent and final procedural success was 91.2%. The median length of the treated segment was 330 ± 96 mm. The median stented segment was 366 ± 71 mm and the mean number of the stents was 2.1 ± 0.9. At 1 year, primary and secondary patency rates were 63.9% and 82.1%, respectively. Major adverse cardiovascular events occurred in 11 patients (22.9%), and[[strike_start]] [[strike_end]]significant benefits were observed in Rutherford class and walking distance (both P < 0.001). Conclusions Primary implantation of self-expanding nitinol stents for the treatment of TASC D femoropopliteal lesions appears to be safe and effective, especially in patients who have multiple co-morbidities and a high risk for surgical bypass. The risk of restenosis was higher when long stenting was extended to the popliteal artery.

An adaptable pentaloop defines a robust neomycin-B RNA aptamer with conditional ligand-bound structures.

Aptamers can be highly specific for their targets, which implies precise molecular recognition between aptamer and target. However, as small polymers, their structures are more subject to environmental conditions than the more constrained longer RNAs such as those that constitute the ribosome. To understand the balance between structural and environmental factors in establishing ligand specificity of aptamers, we examined the RNA aptamer (NEO1A) previously reported as specific for neomycin-B. We show that NEO1A can recognize other aminoglycosides with similar affinities as for neomycin-B and its aminoglycoside specificity is strongly influenced by ionic strength and buffer composition. NMR and 2-aminopurine (2AP) fluorescence studies of the aptamer identified a flexible pentaloop and a stable binding pocket. Consistent with a well-structured binding pocket, docking analysis results correlated with experimental measures of the binding energy for most ligands. Steady state fluorescence studies of 2AP-substituted aptamers confirmed that A16 moves to a more solvent accessible position upon ligand binding while A14 moves to a less solvent accessible position, which is most likely a base stack. Analysis of binding affinities of NEO1A sequence variants showed that the base in position 16 interacts differently with each ligand and the interaction is a function of the buffer constituents. Our results show that the pentaloop provides NEO1A with the ability to adapt to external influences on its structure, with the critical base at position 16 adjusting to incorporate each ligand into a stable pocket by hydrophobic interactions and/or hydrogen bonds depending on the ligand and the ionic environment.

The effects of air pollution and weather conditions on the incidence of acute myocardial infarction.

OBJECTIVE: In this retrospective study, we investigated the association between air pollution and weather conditions with the incidence of acute myocardial infarction (AMI) in the city of Kutahya. METHODS: A total of 402 patients who were admitted with acute ST segment elevation MI and non-ST segment elevation MI were included in the study in 1 year. Daily maximum, minimum, and mean ambient temperature and mean barometric pressure data were obtained from the Kutahya Meteorology Department. Daily air pollution data were obtained from the Web site of National Air Quality Observation Network (http://www.havaizleme.gov.tr). RESULTS: Increase in ambient air temperature in the day of MI and 2 days before the day of MI according to their control days was correlated with increase in number of MI cases. When we grouped the patients according to ages as 30-54, 55-65, and >65 years, we found that there was a relation between sulfur dioxide (SO2) and the occurrence of AMI for the age group of 30-54 for the same day (D0) (P<.017). The number of AMIs was the lowest in fall season, whereas the number of AMIs was the highest in winter season. CONCLUSION: There was no statistically significant association between the particulates with diameter b=10 µm, SO2 concentrations, air pressure, and the risk of AMI, but there was statistically significant relation between occurrence of MI and SO2 for the patients under age of 55 years. The number of AMIs was the lowest in fall season, whereas the number of AMIs was the highest in winter season.

Intracoronary epinephrine in the treatment of refractory no-reflow after primary percutaneous coronary intervention: a retrospective study.

BACKGROUND: Despite the advances in medical and interventional treatment modalities, some patients develop epicardial coronary artery reperfusion but not myocardial reperfusion after primary percutaneous coronary intervention (PCI), known as no-reflow. The goal of this study was to evaluate the safety and efficacy of intracoronary epinephrine in reversing refractory no-reflow during primary PCI. METHODS: A total of 248 consecutive STEMI patients who had undergone primary PCI were retrospectively evaluated. Among those, 12 patients which received intracoronary epinephrine to treat a refractory no-reflow phenomenon were evaluated. Refractory no-reflow was defined as persistent TIMI flow grade (TFG) ≤ 2 despite intracoronary administration of at least one other pharmacologic intervention. TFG, TIMI frame count (TFC), and TIMI myocardial perfusion grade (TMPG) were recorded before and after intracoronary epinephrine administration. RESULTS: A mean of 333 ± 123 mcg of intracoronary epinephrine was administered. No-reflow was successfully reversed with complete restoration of TIMI 3 flow in 9 of 12 patients (75%). TFG improved from 1.33 ± 0.49 prior to epinephrine to 2.66 ± 0.65 after the treatment (p < 0.001). There was an improvement in coronary flow of at least one TFG in 11 (93%) patients, two TFG in 5 (42%) cases. TFC decreased from 56 ± 10 at the time of no-reflow to 19 ± 11 (p < 0.001). A reduction of TMPG from 0.83 ± 0.71 to 2.58 ± 0.66 was detected after epinephrine bolus (p < 0.001). Epinephrine administration was well tolerated without serious adverse hemodynamic or chronotropic effects. Intracoronary epinephrine resulted in significant but tolerable increase in heart rate (68 ± 13 to 95 ± 16 beats/min; p < 0.001) and systolic blood pressure (94 ± 18 to 140 ± 20; p < 0.001). Hypotension associated with no-reflow developed in 5 (42%) patients. During the procedure, intra-aortic balloon pump counterpulsation was required in two (17%) patients, transvenous pacing in 2 (17%) cases, and both intra-aortic balloon counterpulsation and transvenous pacing in one (8%) patients. One patient (8%) died despite all therapeutic measures. CONCLUSION: Intracoronary epinephrine may become an effective alternative in patients suffering refractory no-reflow following primary PCI.