IT-Related Barriers and Facilitators to the Implementation of a New European eHealth Solution, the Digital Survivorship Passport (SurPass Version 2.0): Semistructured Digital Survey.

BACKGROUND: To overcome knowledge gaps and optimize long-term follow-up (LTFU) care for childhood cancer survivors, the concept of the Survivorship Passport (SurPass) has been invented. Within the European PanCareSurPass project, the semiautomated and interoperable SurPass (version 2.0) will be optimized, implemented, and evaluated at 6 LTFU care centers representing 6 European countries and 3 distinct health system scenarios: (1) national electronic health information systems (EHISs) in Austria and Lithuania, (2) regional or local EHISs in Italy and Spain, and (3) cancer registries or hospital-based EHISs in Belgium and Germany. OBJECTIVE: We aimed to identify and describe barriers and facilitators for SurPass (version 2.0) implementation concerning semiautomation of data input, interoperability, data protection, privacy, and cybersecurity. METHODS: IT specialists from the 6 LTFU care centers participated in a semistructured digital survey focusing on IT-related barriers and facilitators to SurPass (version 2.0) implementation. We used the fit-viability model to assess the compatibility and feasibility of integrating SurPass into existing EHISs. RESULTS: In total, 13/20 (65%) invited IT specialists participated. The main barriers and facilitators in all 3 health system scenarios related to semiautomated data input and interoperability included unaligned EHIS infrastructure and the use of interoperability frameworks and international coding systems. The main barriers and facilitators related to data protection or privacy and cybersecurity included pseudonymization of personal health data and data retention. According to the fit-viability model, the first health system scenario provides the best fit for SurPass implementation, followed by the second and third scenarios. CONCLUSIONS: This study provides essential insights into the information and IT-related influencing factors that need to be considered when implementing the SurPass (version 2.0) in clinical practice. We recommend the adoption of Health Level Seven Fast Healthcare Interoperability Resources and data security measures such as encryption, pseudonymization, and multifactor authentication to protect personal health data where applicable. In sum, this study offers practical insights into integrating digital health solutions into existing EHISs.

Scaling up and implementing the digital Survivorship Passport tool in routine clinical care - The European multidisciplinary PanCareSurPass project.

BACKGROUND: Childhood cancer survivors (CCS), of whom there are about 500,000 living in Europe, are at an increased risk of developing health problems [1-6] and require lifelong Survivorship Care. There are information and knowledge gaps among CCS and healthcare providers (HCPs) about requirements for Survivorship Care [7-9] that can be addressed by the Survivorship Passport (SurPass), a digital tool providing CCS and HCPs with a comprehensive summary of past treatment and tailored recommendations for Survivorship Care. The potential of the SurPass to improve person-centred Survivorship Care has been demonstrated previously [10,11]. METHODS: The EU-funded PanCareSurPass project will develop an updated version (v2.0) of the SurPass allowing for semi-automated data entry and implement it in six European countries (Austria, Belgium, Germany, Italy, Lithuania and Spain), representative of three infrastructure healthcare scenarios typically found in Europe. The implementation study will investigate the impact on person-centred care, as well as costs and processes of scaling up the SurPass. Interoperability between electronic health record systems and SurPass v2.0 will be addressed using the Health Level Seven (HL7) International interoperability standards. RESULTS: PanCareSurPass will deliver an interoperable digital SurPass with comprehensive evidence on person-centred outcomes, technical feasibility and health economics impacts. An Implementation Toolkit will be developed and freely shared to promote and support the future implementation of SurPass across Europe. CONCLUSIONS: PanCareSurPass is a novel European collaboration that will improve person-centred Survivorship Care for CCS across Europe through a robust assessment of the implementation of SurPass v2.0 in different healthcare settings.

Barriers and facilitators to implementation of the interoperable Survivorship Passport (SurPass) v2.0 in 6 European countries: a PanCareSurPass online survey study.

PURPOSE: Long-term follow-up (LTFU) care for childhood cancer survivors (CCSs) is essential to improve and maintain their quality of life. The Survivorship Passport (SurPass) is a digital tool which can aid in the delivery of adequate LTFU care. During the European PanCareSurPass (PCSP) project, the SurPass v2.0 will be implemented and evaluated at six LTFU care clinics in Austria, Belgium, Germany, Italy, Lithuania and Spain. We aimed to identify barriers and facilitators to the implementation of the SurPass v2.0 with regard to the care process as well as ethical, legal, social and economical aspects. METHODS: An online, semi-structured survey was distributed to 75 stakeholders (LTFU care providers, LTFU care program managers and CCSs) affiliated with one of the six centres. Barriers and facilitators identified in four centres or more were defined as main contextual factors influencing implementation of SurPass v2.0. RESULTS: Fifty-four barriers and 50 facilitators were identified. Among the main barriers were a lack of time and (financial) resources, gaps in knowledge concerning ethical and legal issues and a potential increase in health-related anxiety in CCSs upon receiving a SurPass. Main facilitators included institutions' access to electronic medical records, as well as previous experience with SurPass or similar tools. CONCLUSIONS: We provided an overview of contextual factors that may influence SurPass implementation. Solutions should be found to overcome barriers and ensure effective implementation of SurPass v2.0 into routine clinical care. IMPLICATIONS FOR CANCER SURVIVORS: These findings will be used to inform on an implementation strategy tailored for the six centres.

Factors Influencing Implementation of the Survivorship Passport: The IT Perspective.

Compared to the general population, childhood cancer survivors represent a vulnerable population as they are at increased risk of developing health problems, known as late effects, resulting in excess morbidity and mortality. The Survivorship Passport aims to capture key health data about the survivors and their treatment, as well as personalized recommendations and a care plan with the aim to support long-term survivorship care. The PanCareSurPass (PCSP) project building on the experience gained in an earlier implementation in Giannina Gaslini Institute, Italy, will implement and rigorously assess an integrated, HL7 FHIR based, implementation of the Survivorship Passport. The six implementation countries, namely Austria, Belgium, Germany, Italy, Lithuania, and Spain, are supported by different national or regional digital health infrastructures and Electronic Medical Record (EMR) systems. Semi structured interviews were carried out to explore potential factors affecting implementation, identify use cases, and coded data that can be semi-automatically transferred from the EMR to SurPass. This paper reflects on findings of these interviews and confirms the need for a multidisciplinary and multi-professional approach towards a sustainable and integrated large-scale implementation of the Survivorship Passport across Europe.

Machine Learning Based Walking Aid Detection in Timed Up-and-Go Test Recordings of Elderly Patients.

Frailty and falls are the main causes of morbidity and disability in elderly people. The Timed Up-and-Go (TUG) test has been proposed as an appropriate method for evaluating elderly individuals' risk of falling. To analyze the TUG's potential for falls prediction, we conducted a clinical study with participants aged ≥ 65 years, living in nursing homes. We harvested 138 TUG recordings with the information, if patients used a walking aid or not and developed a method to predict the use of walking aids using a Random Forest Classifier for ultrasonic based TUG test recordings. We achieved a high accuracy with an Area Under the Curve (AUC) of 96,9% using a 20% leave out evaluation strategy. Automated collection of structured data from TUG recordings - like the use of a walking aid - may help to improve fall risk tools in future.

Development of Multivariable Models to Predict and Benchmark Transfusion in Elective Surgery Supporting Patient Blood Management.

BACKGROUND: Blood transfusion is a highly prevalent procedure in hospitalized patients and in some clinical scenarios it has lifesaving potential. However, in most cases transfusion is administered to hemodynamically stable patients with no benefit, but increased odds of adverse patient outcomes and substantial direct and indirect cost. Therefore, the concept of Patient Blood Management has increasingly gained importance to pre-empt and reduce transfusion and to identify the optimal transfusion volume for an individual patient when transfusion is indicated. OBJECTIVES: It was our aim to describe, how predictive modeling and machine learning tools applied on pre-operative data can be used to predict the amount of red blood cells to be transfused during surgery and to prospectively optimize blood ordering schedules. In addition, the data derived from the predictive models should be used to benchmark different hospitals concerning their blood transfusion patterns. METHODS: 6,530 case records obtained for elective surgeries from 16 centers taking part in two studies conducted in 2004-2005 and 2009-2010 were analyzed. Transfused red blood cell volume was predicted using random forests. Separate models were trained for overall data, for each center and for each of the two studies. Important characteristics of different models were compared with one another. RESULTS: Our results indicate that predictive modeling applied prior surgery can predict the transfused volume of red blood cells more accurately (correlation coefficient cc = 0.61) than state of the art algorithms (cc = 0.39). We found significantly different patterns of feature importance a) in different hospitals and b) between study 1 and study 2. CONCLUSION: We conclude that predictive modeling can be used to benchmark the importance of different features on the models derived with data from different hospitals. This might help to optimize crucial processes in a specific hospital, even in other scenarios beyond Patient Blood Management.

Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial.

BACKGROUND: High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. METHODS: We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients with high-risk neuroblastoma at 128 institutions in 18 countries that included an open-label randomised arm in which high-dose chemotherapy regimens were compared. Patients (age 1-20 years) with neuroblastoma were eligible to be randomly assigned if they had completed a multidrug induction regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide with or without topotecan, vincristine, and doxorubicin) and achieved an adequate disease response. Patients were randomly assigned (1:1) to busulfan and melphalan or to carboplatin, etoposide, and melphalan by minimisation, balancing age at diagnosis, stage, MYCN amplification, and national cooperative clinical group between groups. The busulfan and melphalan regimen comprised oral busulfan (150 mg/m2 given on 4 days consecutively in four equal doses); after Nov 8, 2007, intravenous busulfan was given (0·8-1·2 mg/kg per dose for 16 doses according to patient weight). After 24 h, an intravenous melphalan dose (140 mg/m2) was given. Doses of busulfan and melphalan were modified according to bodyweight. The carboplatin, etoposide, and melphalan regimen consisted of carboplatin continuous infusion of area under the plasma concentration-time curve 4·1 mg/mL per min per day for 4 days, etoposide continuous infusion of 338 mg/m2 per day for 4 days, and melphalan 70 mg/m2 per day for 3 days, with doses for all three drugs modified according to bodyweight and glomerular filtration rate. Stem-cell rescue was given after the last dose of high-dose chemotherapy, at least 24 h after melphalan in patients who received busulfan and melphalan and at least 72 h after carboplatin etoposide, and melphalan. All patients received subsequent local radiotherapy to the primary tumour site followed by maintenance therapy. The primary endpoint was 3-year event-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704716, and EudraCT, number 2006-001489-17. FINDINGS: Between June 24, 2002, and Oct 8, 2010, 1347 patients were enrolled and 676 were eligible for random allocation, 598 (88%) of whom were randomly assigned: 296 to busulfan and melphalan and 302 to carboplatin, etoposide, and melphalan. Median follow-up was 7·2 years (IQR 5·3-9·2). At 3 years, 146 of 296 patients in the busulfan and melphalan group and 188 of 302 in the carboplatin, etoposide, and melphalan group had an event; 3-year event-free survival was 50% (95% CI 45-56) versus 38% (32-43; p=0·0005). Nine patients in the busulfan and melphalan group and 11 in the carboplatin, etoposide, and melphalan group had died without relapse by 5 years. Severe life-threatening toxicities occurred in 13 (4%) patients who received busulfan and melphalan and 29 (10%) who received carboplatin, etoposide, and melphalan. The most frequent grade 3-4 adverse events were general condition (74 [26%] of 281 in the busulfan and melphalan group vs 103 [38%] of 270 in the carboplatin, etoposide, and melphalan group), infection (55 [19%] of 283 vs 74 [27%] of 271), and stomatitis (138 [49%] of 284 vs 162 [59%] of 273); 60 (22%) of 267 patients in the busulfan and melphalan group had Bearman grades 1-3 veno-occlusive disease versus 21 (9%) of 239 in the carboplatin, etoposide, and melphalan group. INTERPRETATION: Busulfan and melphalan improved event-free survival in children with high-risk neuroblastoma with an adequate response to induction treatment and caused fewer severe adverse events than did carboplatin, etoposide, and melphalan. Busulfan and melphalan should thus be considered standard high-dose chemotherapy and ongoing randomised studies will continue to aim to optimise treatment for high-risk neuroblastoma. FUNDING: European Commission 5th Framework Grant and the St Anna Kinderkrebsforschung.

Gender disparities in red blood cell transfusion in elective surgery: a post hoc multicentre cohort study.

OBJECTIVES: A post hoc gender comparison of transfusion-related modifiable risk factors among patients undergoing elective surgery. SETTINGS: 23 Austrian centres randomly selected and stratified by region and level of care. PARTICIPANTS: We consecutively enrolled in total 6530 patients (3465 women and 3065 men); 1491 underwent coronary artery bypass graft (CABG) surgery, 2570 primary unilateral total hip replacement (THR) and 2469 primary unilateral total knee replacement (TKR). MAIN OUTCOME MEASURES: Primary outcome measures were the number of allogeneic and autologous red blood cell (RBC) units transfused (postoperative day 5 included) and differences in intraoperative and postoperative transfusion rate between men and women. Secondary outcomes included perioperative blood loss in transfused and non-transfused patients, volume of RBCs transfused, perioperative haemoglobin values and circulating red blood volume on postoperative day 5. RESULTS: In all surgical groups, the transfusion rate was significantly higher in women than in men (CABG 81 vs 49%, THR 46 vs 24% and TKR 37 vs 23%). In transfused patients, the absolute blood loss was higher among men in all surgical categories while the relative blood loss was higher among women in the CABG group (52.8 vs 47.8%) but comparable in orthopaedic surgery. The relative RBC volume transfused was significantly higher among women in all categories (CABG 40.0 vs 22.3; TKR 25.2 vs 20.2; THR 26.4 vs 20.8%). On postoperative day 5, the relative haemoglobin values and the relative circulating RBC volume were higher in women in all surgical categories. CONCLUSIONS: The higher transfusion rate and volume in women when compared with men in elective surgery can be explained by clinicians applying the same absolute transfusion thresholds irrespective of a patient's gender. This, together with the common use of a liberal transfusion strategy, leads to further overtransfusion in women.

IT Infrastructure for Merging Data from Different Clinical Trials and Across Independent Research Networks.

Opsoclonus Myoclonus Syndrome (OMS) is a rare disease in children which is often associated with neuroblastoma and, therefore, requires treatment by pediatric neurologists and oncologists. The ongoing OMS trial investigates questions related to OMS and potentially underlying neuroblastomas. To support this trial with an adequate IT infrastructure, linkage of neuroblastoma research databases with the OMS electronic data capture (EDC) system was required. Therefore, an EDC system for the OMS trial was developed and integrated into the research infrastructure of the European Network for Cancer Research in Children and Adolescents (ENCCA) project. Application of ENNCA's pseudonymization concept enabled linkage of the OMS trial with neuroblastoma trials from two different scientific societies, while being compliant with current data protection regulations. Linkage of the neurological and the oncological domain could successfully be demonstrated and a promising concept for secondary use of the data of both domains has been developed, proofing the broad potential of the concepts for cross-domain research as promoted in the ENCCA project.

Data Driven Methods for Predicting Blood Transfusion Needs in Elective Surgery.

Research in blood transfusions mainly focuses on Donor Blood Management, including donation, screening, storage and transport. However, the last years saw an increasing interest in recipient related optimizations, i.e. Patient Blood Management (PBM). Although PBM already aims at reducing transfusion rates by pre- and intra-surgical optimization, there is still a high potential of improvement on an individual level. The present paper investigates the feasibility of predicting blood transfusions needs based on datasets from various treatment phases, using data which have been collected in two previous studies. Results indicate that prediction of blood transfusions can be further improved by predictive modelling including individual pre-surgical parameters. This also allows to identify the main predictors influencing transfusion practice. If confirmed in a prospective dataset, these or similar predictive methods could be a valuable tool to support PBM with the ultimate goal to reduce costs and improve patient outcomes.

Interoperability Architecture for a Paediatric Oncology European Reference Network.

With the Directive 2011/24/EU on patients' rights in cross-border healthcare and the related delegated decisions, the European Commission defined a legal framework on how healthcare shall be organised by European Union (EU) member states (MS) where patients can move beyond the borders of their home country. Among other aspects, Article 12 of the directive is concerned with supporting MS with the development of so called European Reference Networks (ERN), dedicated to the treatment of "patients with a medical condition requiring a particular concentration of expertise in medical domains where expertise is rare". In the "European Expert Paediatric Oncology Reference Network for Diagnostics and Treatment" (ExPO-r-Net) project, the establishment of such an ERN in the domain of Paediatric Oncology is currently piloted. The present paper describes the high level use cases, the main requirements and a corresponding interoperability architecture capable to serve as the necessary IT platform to facilitate cross-border health data exchange.

Electronic Patient Reported Outcomes in Paediatric Oncology - Applying Mobile and Near Field Communication Technology.

BACKGROUND: Electronic Patient Reported Outcomes (ePRO) gathered using telemonitoring solutions might be a valuable source of information in rare cancer research. OBJECTIVES: The objective of this paper was to develop a concept and implement a prototype for introducing ePRO into the existing neuroblastoma research network by applying Near Field Communication and mobile technology. METHODS: For physicians, an application was developed for registering patients within the research network and providing patients with an ID card and a PIN for authentication when transmitting telemonitoring data to the Electronic Data Capture system OpenClinica. For patients, a previously developed telemonitoring system was extended by a Simple Object Access Protocol (SOAP) interface for transmitting nine different health parameters and toxicities. RESULTS: The concept was fully implemented on the front-end side. The developed application for physicians was prototypically implemented and the mobile application of the telemonitoring system was successfully connected to OpenClinica. Future work will focus on the implementation of the back-end features.

Standardized data sharing in a paediatric oncology research network--a proof-of-concept study.

Data that has been collected in the course of clinical trials are potentially valuable for additional scientific research questions in so called secondary use scenarios. This is of particular importance in rare disease areas like paediatric oncology. If data from several research projects need to be connected, so called Core Datasets can be used to define which information needs to be extracted from every involved source system. In this work, the utility of the Clinical Data Interchange Standards Consortium (CDISC) Operational Data Model (ODM) as a format for Core Datasets was evaluated and a web tool was developed which received Source ODM XML files and--via Extensible Stylesheet Language Transformation (XSLT)--generated standardized Core Dataset ODM XML files. Using this tool, data from different source systems were extracted and pooled for joined analysis in a proof-of-concept study, facilitating both, basic syntactic and semantic interoperability.

Architecture for an advanced biomedical collaboration domain for the European paediatric cancer research community (ABCD-4-E).

Today, progress in biomedical research often depends on large, interdisciplinary research projects and tailored information and communication technology (ICT) support. In the context of the European Network for Cancer Research in Children and Adolescents (ENCCA) project the exchange of data between data source (Source Domain) and data consumer (Consumer Domain) systems in a distributed computing environment needs to be facilitated. This work presents the requirements and the corresponding solution architecture of the Advanced Biomedical Collaboration Domain for Europe (ABCD-4-E). The proposed concept utilises public as well as private cloud systems, the Integrating the Healthcare Enterprise (IHE) framework and web-based applications to provide the core capabilities in accordance with privacy and security needs. The utility of crucial parts of the concept was evaluated by prototypic implementation. A discussion of the design indicates that the requirements of ENCCA are fully met. A whole system demonstration is currently being prepared to verify that ABCD-4-E has the potential to evolve into a domain-bridging collaboration platform in the future.

An mHealth system for toxicity monitoring of paediatric oncological patients using Near Field Communication technology.

Home-based monitoring might be useful to reduce the burden of long-lasting oncological treatment for children. Current telemonitoring applications focus on chronic diseases or elderly people. Based on the workflow for different stakeholders and the identification of parameters important in paediatric oncology, we developed a prototype of a smartphone-based telehealth system using Near Field Communication technology for monitoring paediatric neuroblastoma patients at home. The parameters blood pressure, heart rate, temperature, body weight, C-reactive protein, white blood cell count, wellbeing, pain level, nausea level and skin alterations could be monitored using a smartphone, a designated app, point-of-care measurement devices and a smart-poster containing RFID tags. The system has been designed to increase the quality of life for paediatric cancer patients. As a future step, a clinical trial is currently being planned to evaluate the system in clinical setting.

Patient identity management for secondary use of biomedical research data in a distributed computing environment.

Dealing with data from different source domains is of increasing importance in today's large scale biomedical research endeavours. Within the European Network for Cancer research in Children and Adolescents (ENCCA) a solution to share such data for secondary use will be established. In this paper the solution arising from the aims of the ENCCA project and regulatory requirements concerning data protection and privacy is presented. Since the details of secondary biomedical dataset utilisation are often not known in advance, data protection regulations are met with an identity management concept that facilitates context-specific pseudonymisation and a way of data aggregation using a hidden reference table later on. Phonetic hashing is proposed to prevent duplicated patient registration and re-identification of patients is possible via a trusted third party only. Finally, the solution architecture allows for implementation in a distributed computing environment, including cloud-based elements.

Development of an electronic database for quality assurance of radiotherapy in the International Society of Paediatric Oncology (Europe) high risk neuroblastoma study.

Quality assurance of radiotherapy is an important determinant of outcome in some cancers. SIOPEN-R-NET developed a computerised remote data entry system for recording imaging and treatment parameters for its multimodality high risk neuroblastoma study. This will enable investigation of the relationship between radiotherapy quality and local control.

Randomized Trial of prophylactic granulocyte colony-stimulating factor during rapid COJEC induction in pediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study.

PURPOSE: To reduce the incidence of febrile neutropenia during rapid COJEC (cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide given in a rapid delivery schedule) induction. In the High-Risk Neuroblastoma-1 (HR-NBL1) trial, the International Society of Paediatric Oncology European Neuroblastoma Group (SIOPEN) randomly assigned patients to primary prophylactic (PP) versus symptom-triggered granulocyte colony-stimulating factor (GCSF; filgrastim). PATIENTS AND METHODS: From May 2002 to November 2005, 239 patients in 16 countries were randomly assigned to receive or not receive PPGCSF. There were 144 boys with a median age of 3.1 years (range, 1 to 17 years) of whom 217 had International Neuroblastoma Staging System (INSS) stage 4 and 22 had stage 2 or 3 MYCN-amplified disease. The prophylactic arm received a single daily dose of 5 microg/kg GCSF, starting after each of the eight COJEC chemotherapy cycles and stopping 24 hours before the next cycle. Chemotherapy was administered every 10 days regardless of hematologic recovery, provided that infection was controlled. RESULTS: The PPGCSF arm had significantly fewer febrile neutropenic episodes (P = .002), days with fever (P = .004), hospital days (P = .017), and antibiotic days (P = .001). Reported Common Toxicity Criteria (CTC) graded toxicity was also significantly reduced: infections per cycle (P = .002), fever (P < .001), severe leucopenia (P < .001), neutropenia (P < .001), mucositis (P = .002), nausea/vomiting (P = .045), and constipation (P = .008). Severe weight loss was reduced significantly by 50% (P = .013). Protocol compliance with the rapid induction schedule was also significantly better in the PPGCSF arm shown by shorter time to completion (P = .005). PPGCSF did not adversely affect response rates or success of peripheral-blood stem-cell harvest. CONCLUSION: Following these results, PPG-GSF was advised for all patients on rapid COJEC induction.

Computerized heart allograft-recipient monitoring: a multicenter study.

Computerized heart allograft recipient monitoring (CHARM) is a unique concept of patient surveillance after heart transplantation (HTx), based on the evaluation of intramyocardial electrograms (IEGMs) recorded non-invasively with telemetric pacemakers. Previous open, single-center studies had indicated a high correlation between CHARM results and clinical findings. The present study was initiated to assess the suitability of CHARM for monitoring the absence of rejection in a blind, multicenter context. During the HTx procedure, telemetric pacemakers and two epimyocardial leads were implanted in 44 patients at four European HTx centers. IEGMs during pacing were recorded and transferred via the Internet to the CHARM computer center, for automatic data processing and extraction of diagnostically relevant information, i.e., the maximum slew rate of the descending part of the repolarization phase of the ventricular evoked response (VER T-slew). The study period comprised the first 6 months after HTx, during which the transplant centers were blind to the CHARM results. A single threshold diagnosis model was prospectively defined to assess the ability of the VER T-slew to indicate clinically significant rejection, which was defined as an endomyocardial biopsy (EMB) grade greater than or equal to 2, according to the grading system of the International Society for Heart and Lung Transplantation. All EMB slides from three centers were reviewed blind by the pathologist of the fourth center in order that agreement among the histological diagnoses at the various centers could be assessed. Totals of 839 follow-ups and 366 EMBs were obtained in 44 patients. Thirty-seven patients were alive at the end of the study period. Age at HTx, EMB grade distribution, and rejection prevalence varied significantly between the centers. Review of the EMB results showed considerable differences with respect to classification of significant rejection. Comparison of average VER T-slew values with and without rejection in the 15 patients who exhibited both states revealed significantly lower values under the influence of rejection (97+/-13% vs 79+/-15%, P<0.0001). Twenty out of the 25 cases with significant rejection were correctly identified by VER T-slew values below a threshold of 98% (sensitivity =80%, specificity =50%, negative predictive value =97%, positive predictive value =11%; P<0.0005). Of the EMBs, 48% could have been saved if the diagnosis model had been used to indicate the need for EMB. A high negative predictive value for the detection of cases with significant rejection has been obtained in a prospective, blind, multicenter study. The presented method can, therefore, be used to supplement patient monitoring after HTx non-invasively, in particular to indicate the need for EMBs. In centers with patient management similar to the ones who participated in the study, this may allow a reduction in the number of surveillance EMBs.

A resposta ventricular evocada nos pacientes com miocardiopatia hipertrófica obstrutiva tratados com marcapasso DDD / Ventricular evoked response in patients with hypertrophic obstructive cardiomyopathy treated with DDD pacing

Objective - To assess the changes in ventricular evoked responses (VER) produced by the decrease in left ventricular outflow tract gradient (LVOTG) in patients with hypertrophic obstructive cardiomyopathy (HOCM) treated with dual-chamber (DDD) pacing. Methods - A pulse generator Physios CTM (Biotronik, Germany) was implanted in 9 patents with severe drug-refractory HOCM. After implantation, the following conditions were assessed: 1) Baseline evaluation: different AV delay (ranging from 150ms to 50 ms) were sequentially programmed during 5 to 10 minutes, and the LVOTG (as determined by Doppler echocardiography) and VER recorded; 2) standard evaluation, when the best AV de lay (resulting in the lowest LVOTG) programmed at the initial evaluation was maintained so that its effect on VER and LVOTG could be assessed during each chronic pacing evaluation. Results - LVOTG decreased after DDD pacing, with a mean value of 59 + 24 mmHg after dual chamber pacemaker, which was significantly less than the gradient before pacing (98 + 22mmHg). An AV delay > 100ms produced a significantly lower decrease in VER depolarization duration (VER(DD)) when compared to an AV delay =100ms. Linear regression analyses showed a significant correlation between the LVOTG values and the magnitude of VER (r=0.69; p<0.05) in the 9 studied patients. Conclusion - The telemetry obtained intramyocardial electrogram is a sensitive means to assess left ventricular dynamics in patients with HOCM treated with DDD pacing.