Biomedical subjects

Martin Dugas

Publications and source records attributed to Martin Dugas.

At least 19 recordsLinked to original sources

PubMed2006

Impact of trisomy 8 on expression of genes located on chromosome 8 in different AML subgroups.

Trisomy 8 is the most frequently observed trisomy in acute myeloid leukemia (AML) occurring as a sole karyotype abnormality or in addition to other chromosome aberrations. It was the aim of this study to analyze the impact of trisomy 8 on the expression of genes located on chromosome 8 in distinct AML subgroups characterized by different chromosome abnormalities in addition to trisomy 8. Gene expression analyses were performed on a total of 567 AML cases comprising the following subgroups: +8 sole, +8 within a complex aberrant karyotype, +8 in addition to t(15;17), inv(16), t(8;21), 11q23/MLL, or other abnormalities, AML with normal karyotype and the before mentioned subgroups without trisomy 8. A significant higher mean expression of genes located on chromosome 8 was observed in subgroups with +8 in comparison to their respective control groups. A varying number of significantly higher expressed genes was identified in all comparisons. No gene was significantly overexpressed in all comparisons, and no distinct gene expression pattern was identified allowing the identification of cases with trisomy 8. In conclusion, the gain of chromosome 8 leads to a higher expression of genes located on chromosome 8. However, no consistent pattern of genes was identified, which shows a higher expression in all AML subtypes with trisomy 8. These data suggest that trisomy 8 rather provides a platform for a higher expression of chromosome 8 genes which are individually up-regulated by the respective primary genetic abnormalities. Therefore, trisomy 8 in AML determines no specific disease characteristic but is a disease modulating secondary event.

Acute Disease↗

PubMed2005

Functional profiling of human atrial and ventricular gene expression.

The purpose of our investigation was to identify the transcriptional basis for ultrastructural and functional specialization of human atria and ventricles. Using exploratory microarray analysis (Affymetrix U133A+B), we detected 11,740 transcripts expressed in human heart, representing the most comprehensive report of the human myocardial transcriptome to date. Variation in gene expression between atria and ventricles accounted for the largest differences in this data set, as 3.300 and 2.974 transcripts showed higher expression in atria and ventricles, respectively. Functional classification based on Gene Ontology identified chamber-specific patterns of gene expression and provided molecular insights into the regional specialization of cardiomyocytes, correlating important functional pathways to transcriptional activity: Ventricular myocytes preferentially express genes satisfying contractile and energetic requirements, while atrial myocytes exhibit specific transcriptional activities related to neurohumoral function. In addition, several pro-fibrotic and apoptotic pathways were concentrated in atrial myocardium, substantiating the higher susceptibility of atria to programmed cell death and extracellular matrix remodelling observed in human and experimental animal models of heart failure. Differences in transcriptional profiles of atrial and ventricular myocardium thus provide molecular insights into myocardial cell diversity and distinct region-specific adaptations to physiological and pathophysiological conditions. Moreover, as major functional classes of atrial- and ventricular-specific transcripts were common to human and murine myocardium, an evolutionarily conserved chamber-specific expression pattern in mammalian myocardium is suggested.

Animals↗

PubMed2005

Global approach to the diagnosis of leukemia using gene expression profiling.

Accurate diagnosis and classification of leukemias are the bases for the appropriate management of patients. The diagnostic accuracy and efficiency of present methods may be improved by the use of microarrays for gene expression profiling. We analyzed gene expression profiles in 937 bone marrow and peripheral blood samples from 892 patients with all clinically relevant leukemia subtypes and from 45 nonleukemic controls by U133A and U133B GeneChip arrays. For each subgroup, differentially expressed genes were calculated. Class prediction was performed using support vector machines. Prediction accuracy was estimated by 10-fold cross-validation and was assessed for robustness in a 100-fold resampling approach using randomly chosen test sets consisting of one third of the samples. Applying the top 100 genes of each subgroup, an overall prediction accuracy of 95.1% was achieved that was confirmed by resampling (median, 93.8%; 95% confidence interval, 91.4%-95.8%). In particular, acute myeloid leukemia (AML) with t(15;17), AML with t(8;21), AML with inv(16), chronic lymphatic leukemia (CLL), and pro-B-cell acute lymphoblastic leukemia (pro-B-ALL) with t(11q23) were classified with 100% sensitivity and 100% specificity. Accordingly, cluster analysis completely separated all 13 subgroups analyzed. Gene expression profiling can predict all clinically relevant subentities of leukemia with high accuracy.

Adolescent↗

PubMed2005

Reprogramming of the human atrial transcriptome in permanent atrial fibrillation: expression of a ventricular-like genomic signature.

Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether reexpression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression in patients with sinus rhythm and to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed downregulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile, and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent upregulation of transcripts involved in metabolic activities, suggesting an adaptive response to increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were 5 times more likely to be upregulated in atrial fibrillation (174 genes upregulated, 35 genes downregulated), whereas atrial-specific transcripts were predominantly downregulated (56 genes upregulated, 564 genes downregulated). Overall, in fibrillating atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be upregulated (eg, metabolic processes), whereas functional classes predominantly expressed in atrial myocardium were downregulated (eg, signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium.

Atrial Fibrillation↗

PubMed2005

Beneficial effects of ischemic preconditioning in patients undergoing hepatectomy: the role of neutrophils.

HYPOTHESES: Temporary vascular clampage (Pringle maneuver) during liver surgery can cause ischemia-reperfusion injury. In this process, activation of polymorphonuclear leukocytes (PMNLs) might play a major role. Thus, we investigated the effects of hepatic ischemic preconditioning on PMNL functions. DESIGN: Prospective randomized study. Patients who underwent partial liver resection were randomly assigned to 3 groups: group 1 without Pringle maneuver; group 2 with Pringle maneuver, and group 3 with ischemic preconditioning using 10 minutes of ischemia and 10 minutes of reperfusion prior to Pringle maneuver for resection. SETTING: University hospital, Munich, Germany. PATIENTS: Seventy-five patients underwent hepatic surgery mostly owing to metastasis. MAIN OUTCOME MEASURES: Perioperative factors for PMNL activation, inflammation, and postoperative hepatocellular integrity. RESULTS: Ischemia-reperfusion of the human liver (mean +/- SD time to perform the Pringle maneuver, 35.5 +/- 2.6 minutes) caused (1) a decrease in the number of circulating PMNLs, (2) their intrahepatic sequestration, (3) their systemic activation, and (4) a significant correlation between the degree of their postischemic activation and the postoperative rise in liver enzyme serum levels. In parallel, cytokines with proinflammatory and chemotactic properties were released reaching the highest values when stimulation of PMNLs was most pronounced. When ischemic preconditioning preceded the Pringle maneuver, activation of PMNLs and cytokine plasma levels was reduced as evidenced by the attenuation of superoxide anion production, beta(2)-integrin up-regulation, and interleukin 8 serum concentrations, followed by a significant reduction in serum alanine aminotransferase levels on the first and second postoperative days. CONCLUSIONS: These results demonstrate in humans that ischemic preconditioning reduces activation of PMNLs elicited by the Pringle maneuver. The down-regulation of potentially cytotoxic functions of PMNLs might be one of yet unknown important pathways that altogether mediate protection by ischemic preconditioning.

CD18 Antigens↗

PubMed2005

Pattern robustness of diagnostic gene expression signatures in leukemia.

Microarray technology has been proposed as an addition to the methods in current use for diagnosing leukemia. Before a new technology can be used in a diagnostic setting, the method has to be shown to produce robust results. It is known that, given the technical aspects of specimen sampling and target preparation, global gene expression patterns can change dramatically. Various parameters such as RNA degradation, shipment time, sample purity, and patient age can principally influence measured gene expression. However, thus far, no information has been available on the robustness of a diagnostic gene expression signature. We demonstrate here that for a subset of acute leukemia, expression profiling is applicable in a diagnostic setting, considering various influencing parameters. With the use of a set of differentially expressed genes, that is, a diagnostic gene expression signature, four genetically defined acute myeloid leukemia subtypes with recurrent chromosomal aberrations can clearly be identified. In addition, we show that preparation by different operators and using different sample-handling procedures did not impair the robustness of diagnostic expression signatures. In conclusion, our results provide additional support for the applicability of microarrays in a diagnostic setting, and we have been encouraged to enroll patients in a prospective study in which microarrays will be tested as an additional routine diagnostic method in parallel with standard diagnostic procedures.

Adult↗

PubMed2005

AML M3 and AML M3 variant each have a distinct gene expression signature but also share patterns different from other genetically defined AML subtypes.

Acute promyelocytic leukemia (APL) with t(15;17) appears in two phenotypes: AML M3, with abnormal promyelocytes showing heavy granulation and bundles of Auer rods, and AML M3 variant (M3v), with non- or hypogranular cytoplasm and a bilobed nucleus. We investigated the global gene expression profiles of 35 APL patients (19 AML M3, 16 AML M3v) by using high-density DNA-oligonucleotide microarrays. First, an unsupervised approach clearly separated APL samples from other AMLs characterized genetically as t(8;21) (n = 35), inv(16) (n = 35), or t(11q23)/MLL (n = 35) or as having a normal karyotype (n = 50). Second, we found genes with functional relevance for blood coagulation that were differentially expressed between APL and other AMLs. Furthermore, a supervised pairwise comparison between M3 and M3v revealed differential expression of genes that encode for biological functions and pathways such as granulation and maturation of hematologic cells, explaining morphologic and clinical differences. Discrimination between M3 and M3v based on gene signatures showed a median classification accuracy of 90% by use of 10-fold CV and support vector machines. Additional molecular mutations such as FLT3-LM, which were significantly more frequent in M3v than in M3 (P < 0.0001), may partly contribute to the different phenotypes. However, linear regression analysis demonstrated that genes differentially expressed between M3 and M3v did not correlate with FLT3-LM.

Adolescent↗

PubMed2005

Alpha-gluthathione S-transferase as an early marker of hepatic ischemia/reperfusion injury after liver resection.

Organ dysfunction following liver resection is one of the major postoperative complications of liver surgery. The Pringle maneuver is often applied during liver resection to minimize bleeding, which in turn complicates the postoperative course owing to liver ischemia and reperfusion. Routinely, hepatocellular damage is diagnosed by, for example, abnormal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and the prothrombin time (PT). The cytosolic liver enzyme alpha-glutathione S-transferase (alpha-GST) has recently been shown to have good sensitivity for detecting hepatic injury after acetaminophen poisoning or liver transplantation, but its role in non-transplantation liver surgery has not been assessed. In this prospective randomized clinical study, the diagnostic role of plasma alpha-GST following warm ischemia and reperfusion is reported. A total of 75 patients who underwent liver resection were randomly assigned to three groups: (1) without Pringle (NPR); (2) with Pringle (PR); (3) with ischemic preconditioning by 10 minutes of ischemia and reperfusion each prior to the Pringle manuever (IPC). The major findings are as follows: (1) ALT, AST, and alpha-GST increased upon liver manipulation as early as prior to resection, with a rapid return of alpha-GST values to preoperative levels, whereas ALT and AST further increased on the first postoperative day. (2) In the PR group, alpha-GST, but not ALT and AST, was significantly elevated compared with that in the NPR group at 15 and 30 minutes and 2 hours after resection/reperfusion. In addition, only levels of alpha-GST significantly correlated with the Pringle duration. (3) The ischemia/reperfusion-induced early rise in alpha-GST was completely prevented by ischemic preconditioning. Moreover, only alpha-GST concentrations (> 490 microg L(-1)) determined early after resection (2 hours) predicted postoperative liver dysfunction (24 hours PT < 60%) with a positive predictive value of 74% and a negative predictive value of 76%. Thus alpha-GST seems to be a sensitive, predictive marker of ischemia/reperfusion-induced hepatocellular injury and postoperative liver dysfunction.

Adult↗

PubMed2005

Baseline serum levels of mast cell tryptase are raised in hemodialysis patients and associated with severity of pruritus.

BACKGROUND: The pathogenesis of pruritus in renal disease is not yet understood. Evidence suggests that mast cells play a role; for example, the number of dermal mast cells is increased in patients on hemodialysis. PATIENTS AND METHODS: To investigate a possible role of mast cell tryptase in pruritus of patients undergoing chronic hemodialysis, serum mast cell tryptase concentrations were measured in blood samples taken from 93 such patients, 53 of whom also recorded the severity of their pruritus on a visual analogue scale. RESULTS: Serum mast cell tryptase levels were above 11.4 microg/l (95th percentile) in 84 of 93 hemodialysis patients (90.3 %). The intensity of pruritus correlated significantly (p = 0.014) with the tryptase levels, an associated not yet shown for other mast cell-related parameters. CONCLUSIONS: Mast cells or even tryptase itself may be involved in the pathogenesis of pruritus of hemodialysis patients.

Adolescent↗

PubMed2004

Global gene expression in human myocardium-oligonucleotide microarray analysis of regional diversity and transcriptional regulation in heart failure.

To obtain region- and disease-specific transcription profiles of human myocardial tissue, we explored mRNA expression from all four chambers of eight explanted failing [idiopathic dilated cardiomyopathy (DCM), n=5; ischemic cardiomyopathy (ICM), n=3], and five non-failing hearts using high-density oligonucleotide arrays (Affymetrix U95Av2). We performed pair-wise comparisons of gene expression in the categories (1) atria versus ventricles, (2) disease-regulated genes in atria and (3) disease-regulated genes in ventricles. In the 51 heart samples examined, 549 genes showed divergent distribution between atria and ventricles (272 genes with higher expression in atria, 277 genes with higher expression in ventricles). Two hundred and eighty-eight genes were differentially expressed in failing myocardium compared to non-failing hearts (19 genes regulated in atria and ventricles, 172 regulated in atria only, 97 genes regulated in ventricles only). For disease-regulated genes, down-regulation was 4.5-times more common than up-regulation. Functional classification according to Gene Ontology identified specific biological patterns for differentially expressed genes. Eleven genes were validated by RT-PCR showing a good correlation with the microarray data. Our goal was to determine a gene expression fingerprint of the heart, accounting for region- and disease-specific aspects. Recognizing common gene expression patterns in heart failure will significantly contribute to the understanding of heart failure and may eventually lead to the development of pathway-specific therapies.

Adult↗

PubMed2004

Estimation of liver size for liver transplantation: the impact of age and gender.

In general, the liver is considered to be larger in males than in females. In the present study, data on liver weight from 728 legal autopsies were analyzed with respect to gender, age, body height (BH), body weight (BW), body mass index (BMI), and body surface area (BSA). Descriptive statistics revealed that liver weight increases with age, reaching maximum values between 41 and 50 years in men and between 51 and 60 years in women. Thereafter, liver weight decreases again. Because this loss in liver weight starts earlier in men while liver weight continues to rise in women, the difference in liver weight between men and women is lost above the age of 50. Thus, this age defines a threshold value below which gender is expected to be a critical factor in the calculation of liver weight. When demographic data mentioned above were subjected to multiple stepwise linear regression analysis, liver weight (LW) was best predicted in younger people (16-50 years) by body weight, age, and gender: LW (g) = 452 + 16.34 x BW + 11.85 x age - 166 x gender (r(2) = 0.381; "gender": 1 = female, 0 = male). In contrast, in elderly people (51-70 years) LW was best predicted by BW and age only. Gender was not a significant factor. LW (g) = 1390 + 15.94 x BW - 12.86 x age (r(2) = 0.35). When these formulas were applied to demographic data from 97 organ donors and compared to published formulas (which, however, do not consider the age-dependent effects of gender), the new formulas best predicted male to female liver weight ratios in younger and elderly donors. In conclusion, the new formulas might better predict liver weight in organ donors and transplant recipients to avoid liver size mismatch.

Adolescent↗

PubMed2004

Discrimination of melanocytic tumors by cDNA array hybridization of tissues prepared by laser pressure catapulting.

Gene expression profiling by cDNA array analysis in melanoma is hampered by the need for large amounts of RNA to prepare reliable probes for array hybridization. On the other hand, for ex vivo analysis of malignant cells from melanocytic tumors laser pressure catapulting is an essential prerequisite to obtain noncontaminated melanocytic preparations; however, laser pressure catapulting prepared material provides only nanogram amounts of RNA. In this study we present an approach to overcome these limitations by combining laser pressure catapulting and real-time polymerase chain reaction based SMART cDNA amplification technology. Reproducible and reliable hybridization patterns from about 500 laser pressure catapulting prepared cell equivalents from 22 cases of melanocytic tumors were generated using array analysis. Univariate analysis revealed significant differences of the expression pattern of melanocytic nevi, melanomas, and melanoma metastases. Multivariate analysis with four genes being the best univariate discriminative features (tyrosinase related protein 2, translation initiation factor 2 gamma, ubiquitine conjugating enzyme E2I and one expressed sequence tag) allowed clustering of nevi, melanomas, and melanoma metastases with an accuracy of 82%. Data validation was performed by additional quantitative reverse transcription-polymerase chain reaction (TaqMan-reverse transcription-polymerase chain reaction). Taken together, this study shows, that (1) array analysis is feasible on tumors with rather low cell numbers, and (2) differences in expression profiles allow discrimination between benign and malignant lesions. Expression patterns of marker genes defined in unequivocal histopathologic entities may improve the diagnostic and prognostic assessment of difficult melanocytic lesions, which is still the hardest problem in dermatopathology.

Biopsy↗

PubMed2004

Identification of differentially expressed genes in scrapie-infected mouse brains by using global gene expression technology.

The pathogenesis of prion diseases, a class of transmissible fatal neurodegenerative diseases in humans and animals, is still unclear. The aim of this study was to identify the differentially regulated genes that correlate with the development of prion diseases for a better understanding of their pathological mechanisms. We employed Affymetrix Mouse Expression Arrays 430A containing >22,000 transcripts and compared the global gene expression profiles from brains of mice who were intracerebrally inoculated with scrapie strains ME7 and RML with those from brains of uninfected and mock-infected mice. The microarray data were analyzed by Significance Analysis of Microarrays, revealing 121 genes whose expression increased at least twofold in both ME7- and RML-infected mouse brains, with an estimated false discovery rate of < or =5%. These genes encode proteins involved in proteolysis, protease inhibition, cell growth and maintenance, the immune response, signal transduction, cell adhesion, and molecular metabolism. The time course of expression generally showed up-regulation of these genes from 120 days postinoculation (dpi) for ME7-inoculated mouse brains and from 90 dpi for RML-inoculated mouse brains. The onset of elevated expression correlated temporally with the onset of PrP(Sc) accumulation and the activation of glia, which may have contributed to neuronal cell death. Among the differentially regulated genes reported in the present study, the emergence of genes for several cathepsins and S100 calcium binding proteins was conspicuous. These and other genes reported here may represent novel potential diagnostic and therapeutic targets for prion disease.

Animals↗

PubMed2003

Developmental markers of B cells are superior to those of T cells for identification of stages with distinct gene expression profiles.

B and T lymphocytes develop through a series of cellular stages, which are defined by recombination status of the immunoglobulin and T cell receptor loci and can be separated by analysis of cell-surface markers. We evaluated how well 26 and 41 samples from five and eight developmental stages of B and T cell development, respectively, could be correctly assigned to their lineage of origin and developmental stage by analysis of the expression of 13,026 genes and expressed sequence tags (ESTs). The RNA expression patterns of eight genes correctly classified all 67 samples as belonging to the B cell or to the T cell lineage. Ninety-two to 100% of B-lineage samples could be correctly assigned to the protein-defined developmental stage by the RNA expression pattern of 29 genes. By contrast, RNA expression patterns of 39 genes were necessary to correctly assign 85-100% of T-lineage samples to the correct developmental stage. The sets of genes used for these classifications contain ESTs as well as known genes that have not previously been associated with lymphocyte development. Graphical display of the classifications shows that B-lineage samples are well separated from T-lineage samples, and samples from the five stages of B cell development are well separated from each other. By contrast, samples from the eight stages of T cell development cannot be separated precisely. We conclude that the protein markers currently widely used for separating stages of B cell development better identify molecularly distinct stages than those used for separating stages of T cell development.

Animals↗

PubMed2003

Molecular characterization of acute leukemias by use of microarray technology.

Accurate subclassification of leukemia and the identification of prognostic determinants are essential to guide therapy and to improve patients' outcome. According to present standards, pre-therapeutic assessment depends on a combination of different methods. We aimed to expand the molecular characterization of different acute leukemia subtypes to identify new genome-wide diagnostic markers. Total RNA from 90 adult patients suffering from acute lymphoblastic leukemia (ALL, n = 25) and acute myeloid leukemia (AML, n = 65) was extracted at diagnosis and high density oligonucleotide microarrays were used to analyze the expression profiles of 12,000/22,000 genes in all specimens (Affymetrix U95Av2/U133A). All cases were thoroughly characterized by individual combinations of cytomorphology, cytogenetics, multiparameter immunophenotyping, and molecular genetics. The expression signature of a small set of differentially expressed genes was sufficient to accurately discriminate eight clinically relevant acute leukemia subgroups. Underlying chromosomal aberrations or immunophenotypical characteristics were strictly correlated with a distinct gene expression pattern for AML with t(8;21), t(15;17), t(11q23)/MLL, or inv(16) as well as for precursor B-ALL with t(9;22), t(8;14), or t(11q23)/MLL and precursor T-ALL. These data support a possible future application of microarray technology for classification of the acute leukemias.

Acute Disease↗

PubMed2003

Design and implementation of a common drug information database for a university hospital.

BACKGROUND: Providing high quality problem-oriented drug information relies on the ability to easily collect appropriate background information on clinical cases, to access relevant information from published sources by defined search strategies and to store and retrieve previously answered questions. To do this efficiently, an easy-to-use, flexible and reliable drug information database is necessary. METHODS: We designed and implemented an Intranet-based drug information database for a major university hospital in Germany. The overall design and the technical details of its design are discussed. We developed a generic, XML-based data model for pharmaceutical inquiries including a MeSH-oriented system of 99 pharmaceutical qualifiers to enable efficient indexing of questions and the searching of indexed questions. RESULTS: The system provides query statistics and various search algorithms. The software implementation takes into account recent FDA recommendations for software used in clinical trials; internal review for quality control is supported. The database currently consists of 4224 records after 3.5 years of operation. Each inquiry consists of 50 items, 18 of 50 are categorized; 135 text elements support data entry. Our evaluation is focused on technical feasibility, user acceptance and query patterns. CONCLUSION: The intensive use and widespread acceptance of the database indicates a need for a computerized drug information system and suggests that Intranet technology can perform this task.

Abstracting and Indexing↗

PubMed2003

T-cell receptor excision circles: a novel prognostic parameter for the outcome of transplantation in multiple myeloma patients.

This study investigated whether T-cell receptor excision circles (TRECs) are a prognostic marker for the outcome of myeloma patients undergoing a tandem autologous peripheral blood stem cell transplantation (PBSCT). Twenty-five patients were enrolled. Samples were obtained at study enrollment, after conventional therapy, between first and second transplantation and 3, 6, 12 and 24 months after the second PBSCT. TRECs were quantified using real-time polymerase chain reaction. A high variation in TREC levels was found at diagnosis (median TREC level 136/10(5) peripheral blood mononuclear cells (PBMCs); range 1-1729), suggesting individual differences in thymic output of naive T cells. Patients with more than 136 TRECs/10(5) P BMCs at diagnosis had a statistically significant better overall survival (P=0.05) and event-free survival (P=0.045), whereas low TREC levels correlated with a higher incidence of infectious complications. Median TREC values were lowest after the first PBSCT (52/10(5) PBMCs) and reached the baseline 12 months after the second transplantation. Patients with high TREC levels after the second PBSCT had a significantly higher probability of being in complete or partial remission 30 months after the second PBSCT. TREC levels were not correlated with beta2-microglobulin and C-reactive protein levels at diagnosis. These data suggest that TRECs could be a relevant prognostic factor for patients who receive high-dose chemotherapy and autologous PBSCT.

Adult↗

PubMed2003

Electroanatomic mapping of endocardial right ventricular activation as a guide for catheter ablation in patients with arrhythmogenic right ventricular dysplasia.

Arrhythmogenic right ventricular dysplasia is a structural heart disease characterized by fibrofatty degeneration of right ventricular myocardium and arrhythmias of right ventricular origin. The aim of this study was to characterize endocardial right ventricular activation by electroanatomic mapping as a guide for catheter ablation in patients with arrhythmogenic right ventricular dysplasia. Electroanatomic mapping and entrainment procedures were performed in 5 patients with arrhythmogenic right ventricular dysplasia. Endocardial mapping during ventricular tachycardia demonstrated a focal activation pattern with radial spreading of activation from a site of earliest ventricular activation in all directions. Right ventricular activation time (127 +/- 34 ms) was markedly shorter than tachycardia cycle length (415 +/- 92 ms). The site of earliest ventricular activation was found in an aneurysmal outflow tract (n = 2), at the border of aneurysms near the tricuspid annulus (n = 2), and at the apex of the right ventricle (n = 1). Entrainment mapping criteria of these areas of earliest endocardial activity were consistent with exit sites of a reentrant circuit in an area of abnormal myocardium. Fractionated potentials were found 61 +/- 29 ms before the onset of the QRS complex at these sites. Catheter ablation rendered the "clinical" ventricular tachycardia noninducible in four patients but "nonclinical" faster ventricular tachycardias were inducible in three patients. During the follow-up of 7 +/- 3 months after ablation, the frequency of therapies in 4 patients with an implantable cardioverter defibrillator decreased from 49 +/- 61 episodes per month before ablation, to 0.3 +/- 0.5 episodes per month after ablation (P < 0.05). Electroanatomic mapping during ventricular tachycardia facilitates localization of exit sites in relation to aneurysms in diseased right ventricle and may guide catheter ablation in patients with arrhythmogenic right ventricular dysplasia.

Arrhythmogenic Right Ventricular Dysplasia↗