New Members

[05/02/2017], Shandong University, Shandong Sheng, China Founded in 1901, Shandong University, based in Jinan, China, is the nation’s largest public university. It has prepared over 400,000 individuals in a variety of specialties, and has been making significant contributions to the country’s economic and social development. The growth of the university has allowed it to rise to the forefront of many fields in China. They continually develop new disciplines such as crystal materials, cardiovascular functional recovery, and new drug manufacturing to stay on the cutting edge of scientific research. Many of these newly formed disciplines have quickly risen to the first-class level within the country, and some are even know abroad.

[02/17/2017], University of Porto, Praça de Gomes Teixeira, Portugal The University of Porto, founded in 1911, is a leading scientific and research institution located in Portugal. The university is internationally recognized for the quality of research it produces, and is consistently ranked among the 150 best European universities. It is an important driver of economic, social, and scientific development within Portugal, and strives to be a strong partner of the business community. By combining quality teaching with a focus on market needs, the university strives to actively participate in, and encourage, the progress of communities in which it operates.

[05/24/2016], Marche Polytech University, Ancona, Italy, The Department of Life and Environmental Sciences was established in 2011 by merging a number of laboratories involved in a wide spectrum of fundamental and applied research topics. The department is a center of excellence of the Università Politecnica delle Marche and includes more than 100 scientists and technicians that conduct research in areas such as analytical and organic chemistry, biophysics, cellular and molecular biology, biochemistry and genetics, microbiology and biotechnology, viral, prokaryotic, fungal, algal, plant and animal systematics, physiology and reproduction, marine biology, ecology, eco-toxicology, oceanography, Earth sciences, risk reduction and civil protection.

[05/12/2016], University of Buenos Aires, Buenos Aires, Argentina, Buenos Aires University consists of thirteen colleges/schools, dozens of research institutes, and two secondary schools, offering more than 100 undergraduate majors. There is a teaching staff of 30,000 teachers, and approximately 300,000 students; 30% of scientific research in Argentina takes place at UBA. Standard undergraduate studies last approximately 5 years. Buenos Aires University offers several graduate programmers, masters, PhDs, and specialization courses as well.

[05/12/2016], Queen's University, Kingston, Canada, The mission of Queen's University has been articulated in a number of different forms and formats over the past decade. In all of the presentations, the key elements have remained constant: The University will build on the strength that is Queen's - students, faculty, staff and alumni - to be among the best of internationally known universities in Canada, recognized for: •the exceptional quality of undergraduate and graduate students and programs in the arts, sciences and professions; •the intellectual power and value of research and scholarship by faculty members and students; •the exemplary service of the University and that of its graduates to the community and the nation and the community of nations.

[04/28/2016], University of Leuven, Leuven, Belgium KU Leuven is a research-intensive, internationally oriented university that carries out both fundamental and applied research. It is strongly inter- and multidisciplinary in focus and strives for international excellence. To this end, KU Leuven works together actively with its research partners at home and abroad.KU Leuven encourages personal initiative and critical reflection in a culture of idea exchange, cooperation, solidarity and academic freedom.

[03/07/2016], Mayo Clinic , Rochester, MN,, USA, Mayo Clinic is the first and largest integrated nonprofit medical group practice in the world, employing more than 3,800 physicians and scientists, as well as 50,900 allied health staff. Based out of Rochester, MN, the Mayo Clinic’s mission is “to inspire hope and contribute to health and well-being by providing the best care to every patient through integrated clinical practice, education, and research.” The practice specializes in treating difficult cases through tertiary care, and spends over $500 million a year on research. It was also recognized as one of the best hospitals in the U.S. for 2015-2016 by U.S. News & World Report.

[03/02/2016], Czech Technical University, Prague,, Czech Republic, The Czech Technical University in Prague (CTU) is an internationally recognized higher education and research institution with more than 300 years of tradition and excellence. CTU is a leading technical research university with a large focus on cutting edge science and engineering, paired with a high-quality technical education. With 8 departments each focused on an engineering specialty, the university educates modern specialists, scientists, and managers who are dynamic, flexible, and able to rapidly adapt to the requirements of the market.

[02/10/2016], CERB , Baugy,, France, Located in Baugy, France, CERB was founded in 1973 and has developed into a leading international contract research organization (CRO) in the fields of pre-clinical pharmacology and toxicology. Taking on the challenges of modern drug development, CERB has created a distinctive image as a leading major service provider to the pharmaceutical industry in the context of innovative bio-medical research. CERB takes advantage of its sophisticated synergy between pharmacology and toxicology resources to provide complete pre-phase I packages for new molecules in an economic and timely manner

[01/07/2016], Goergen Institute for Data Science (GIDS), Rochester NY, USA The GIDS supports faculty research, particularly collaborative public-private research partnerships spanning several domains, such as developing health care breakthroughs, improving our knowledge of how the brain works, and creating tools and systems to efficiently use data. The GIDS is working to build strategic alliances and business partnerships among the academic, government, and business communities, leveraging University of Rochester expertise.

[10/06/2015], Dresden University of Technology, Dresden, Germany, Dresden University of Technology is one of eleven German universities that were identified as an “excellent university", and includes over 37,000 students with 14 institutions offering a wide range of academic programs. The Institute of Biomedical Engineering focuses on the early detection, diagnosis, and treatment of life-threatening cardiovascular disease. With a strong focus on research.

[10/06/2015], Biomedical Systems, St. Louis, MO , USA, Biomedical Systems has set the health care industry standard by providing innovative approaches to non-invasive diagnostic services, clinical trials, and products. They provide their clients with the ability to increase cost efficiencies and bring studies to database lock on an advanced timeline by combining over 20 modalities in one study. Biomedical Systems' pioneering spirit is based on a strong history as a privately held company that focuses on clients and people.

[09/15/2015], VivaQuant LLC, St. Paul MN, USA, VivaQuant provides products, services and technology that incorporate advanced signal processing to more accurately extract valuable information from biological signals. Through their technology they are committed to improving the lives of patients and the productivity of clinicians and researchers.

[08/04/2015], Sensium Healthcare Ltd, Oxfordshire, United Kingdom Sensium Healthcare, A global pioneer in wireless monitoring of vital signs. The company focus is on ultra-low power, lightweight, monitoring solutions which improve patient care and safety,shorten hospital stays and reduce healthcare costs.

[07/28/2015], Seoul National University, Gwanak-gu, South Korea, Seoul National University, As Korea leading research university, honoring the ideals of a liberal education aim at teaching students a lifelong love of learning that will form the basis for continuous personal growth. It includes 16 Colleges, 1 Graduate School, 9 Professional Graduate Schools with 16,006 Undergrad Students, 10,559 Graduate Students.

[07/16/2015], Boston Scientific, Marlborough, MA, USA, A leading innovator of medical solutions that improve the health of patients around the world. Products and technologies used to diagnose or treat a wide range of medical conditions, including heart, digestive, pulmonary, vascular, urological, women health and chronic pain conditions. Boston Scientific is dedicated to transforming lives through innovative medical solutions that improve the health of patients around the world.

[09/30/2014], Harvard Medical School-Wyss Institute for Biologically Inspired Engineering, Boston, USA, The Wyss Institute aims to discover the engineering principles that Nature uses to build living things, and harnesses these insights to create biologically inspired materials and devices that will revolutionize healthcare and create a more sustainable world. In medicine, the Institute is developing innovative materials, devices, and disease reprogramming technologies.

[03/12/2014], University Medicine Berlin, Bonn, Germany, The Charite is one of the largest university hospitals in Europe. Here, 3700 doctors and scientists heal, do research and teach at the top international level. More than half of the German Nobel Prize winners in medicine and physiology come from the Charite, among them Emil von Behring, Robert Koch and Paul Ehrlich.

[01/23/2014], BioSign GmbH, Ottenhofen, Germany, Developing innovative measurement and therapy systems for professionals and end-users in the subject area vegetative (autonomic) nervous system. BioSign is responding to the growing medical recognition that disturbances in the autonomic nervous system and disturbances in the interplay of the various organs are involved with the autonomic nervous system.

[11/14/2013], University of Rochester, Computer and Electrical Engineering, Rochester, NY, USA. This department has multiple programs related to energy, to health and medicine, to the connected world, and to music. Specific research programs span a wide range, including medical imaging, image processing, genomics, audio and music signal processing, among others.

[10/31/2013], RIT, Microsystem Engineering, Rochester, USA The multidisciplinary program builds on the fundamentals of traditional engineering and science including the manipulation of electrical, photonic, optical, mechanical, chemical, and biological functionality to process, sense, and interface with the world at a nanometer scale.

[09/10/2013], Medtronic, Inc., Mounds View, USA Medtronic develops and manufactures innovative medical device technology and therapies to treat chronic disease worldwide.

[06/11/2013], RIT, Department of Biomedical Engineering, Rochester, USA The RIT mission is to provide technology-based educational programs for personal and professional development. We rigorously pursue new and emerging career areas. We develop and deliver curricula and advance scholarship relevant to emerging technologies and social conditions. Our community is committed to diversity and student centeredness and is distinguished by our innovative and collaborative spirit.

[05/02/2013], Masonic Medical Research Laboratory, Utica, NY, USA The Masonic Medical Research Laboratory is a not-for-profit institute dedicated to improving the health and quality of life for all. The Laboratory primary mission is to conduct high quality basic and clinical research aimed at generating knowledge and information necessary for development of the medical cures and treatments of tomorrow.

[04/22/2013], Universitat Politecnica de Catalunya (Barcelona-Tech), Barcelona, Spain. The Universitat Politecnica de Catalunya (UPC): BarcelonaTech is a public institution dedicated to higher education and research, specialised in the fields of engineering, architecture and science. With a focus on intellectual rigor, critical thinking, a transversal approach to knowledge, educational innovation and entrepreneurship, the UPC produces competent professionals with the skills they need to tackle present and future challenges.

[03/20/2013], Teschnische Universitat(TU), Dresden, Germany. The TU Dresden is one of eleven German universities that were identified as an Excellence University. TUD has about 36.500 students and almost 5319 employees, 507 professors among them, and, thus, is the largest university in Saxony.

[02/08/2013], Baskir State Pedagogical University (BSPU), Ufa City, Russia M. Akmullah BSPU is a large scientific, educational, cultural and social center of the Republic of Bashkortostan. It includes the Institute of Pedagogics, the Institute of Professional Education and Information Technologies, the Institute of Historical and Legal Education, the Institute of Philological Education and Cross-Cultural Communication and 7 departments with about 12 000 students.

[02/01/2013], Chung-Yuan Christian University, Taiwan, China Chung Yuan Christian University is founded on the spirit of Christian love for the world. With faith, hope, and love, we endeavor to promote higher education for the benefit of the Chinese people, aiming at the pursuit and advancement of genuine knowledge in order to maintain our cultural heritage and, thus, to serve humankind.

[12/11/2012], Cardio-QT Ltd., Glasgow,, United Kingdom Headed by Royal College Accredited Cardiologist and Bioengineer supported by PhD Scientists, Cardio-QT Ltd is an award winning, highly innovative Core Cardiac Analysis Laboratory offering an array of sophisticated validated techniques to solve all analytical research problems.

[10/21/2012], National Polytechnic Institute of Mexico, Mexico City,, Mexico The Institute is the State secular free education institution, guide of public technological education in Mexico. A leader in the generation, application, dissemination and transfer of scientific and technological knowledge.

[09/24/2012], Massachusetts General Hospital, Harvard Medical School , Charlestown, MA,, USA Mass General has long been a leader in successfully bridging innovative science with state-of-the-art clinical medicine. With an annual research budget of nearly $764 million, Mass General conducts the largest hospital-based research program in the United States - a program that spans more than 20 clinical departments and centers across the hospital. This funding drives discoveries and breakthroughs in basic and clinical research, which translate into new and better treatments that transform medical practice and patient care.

[05/24/2012], College of Veterinary Medicine, Cornell University, Ithaca, NY,, USA The mission of the Department of Biomedical Sciences is to educate and inform the veterinary and human biomedical communities through our diverse research and clinical service excellence as well as through our commitment to undergraduate, graduate, and veterinary teaching.

[05/02/2012], The Victor Chang Cardiac Research Institute (VCCRI), Sydney, Australia The VCCRI is committed to excellence in research into heart disease and cardiovascular biology, cardiovascular research training, and facilitating the rapid application of research discoveries to patient care.

[02/09/2012], SAIT, Samsung Advanced Institute of Technology, Gyeonggi,, Korea SAIT provides a full spectrum of support so its researchers can focus on creative research, seek the convergence of heterogeneous technologies and take up new challenges. Meanwhile, SAIT also actively engages in "open innovation" to jointly create future value with other research institutions through collaboration.

[01/26/2012], FDA-CDRH: Center for Devices and Radiological Health, Silver Spring, MD, USA FDA Center for Devices and Radiological Health (CDRH) is responsible for regulating firms who manufacture, repackage, relabel, and/or import medical devices sold in the United States. In addition, CDRH regulates radiation-emitting electronic products (medical and non-medical) such as lasers, x-ray systems, ultrasound equipment, microwave ovens and color televisions.

[01/10/2012], Department of Physiological Nursing, University of California, San Francisco, CA, , USA The Mission of the Department of Physiological Nursing prevention of UCSF is to study the prevention, measurement, and treatment of physiological and biobehavioral responses to health, illness/disease and aging. Psycho-physiological interrelationships and interventions also are studied. Research spans all phases of the health/illness trajectory including people who are healthy, critically ill, living with a chronic illness, and those at the end of life.

[01/03/2012], University of Bologna (HST-ICIR) , Bologna,, Italy The University of Bologna was probably the first University in the western world. Its history is one of great thinkers in science and the humanities, making it an indispensable point of reference in the panorama of European culture. Bologna has thus been called upon to forge relationships with institutions in the most advanced countries to modernise and expand its activity. Among the many challenges which it has met with success, Bologna committed itself to the European dimension which has now led to adoption of the new university system.

PRESS CENTER

[09/23/2010]: AstraZeneca joins the THEW to further cardiac safety inThe Medical News: here.

[12/16/2009]: The Director of the THEW interviewed by Technology Review published by the MIT: here.

[11/11/2009]: New Research Center to Focus on Cardiac Safety and Innovation in Pharmaceutical Industry Today: here.

[6/11/2009]: University of of Rochester and FDA Partner for ECG Database, Drug Discovery & Development Magazine. More info here

[5/6/2009] FDA website Existing Partnerships FDAs Public-Private Partnership Program: THEW

[03/28/2009] Public and Private part- nership to help determine Clinical Biomarker Utility in Applied Clinical Trials online.com.>here

Newsletter Issue 10, october 2010

QT evaluation for drugs with autonomic effects (PART II): QT/RR relationship and QT hysteresis

thewNews


Major step forward: the FDA has committed resources to the development of tools for Holter ECG analytics in thorough QT studies.

by JP. Couderc, PhD

A couple of weeks ago the FDA released information about enabling the use of continuous Holter 12-lead ECGs in the existing ECG warehouse currrently limited to extracted HL7 aECG recordings. This development is described by the Agency as ".. the first step in positioning the FDA to request the upload of continuous recordings as part of the cardiac safety regulatory review process"[1]. Meanwhile next month, a former student from the THEW Educational Program will start a two-year fellowship aiming at the development of Holter-based quality metrics for the review of Holter data from thorough QT studies at the CDER on the FDA campus (Silver Spring, MD).

This interest of the Agency for continuous ECG recordings seems to be driven primarily by the need for a better assessment of the role of autonomic regulation and heart rate on QT interval measurements in thorough QT studies. As we have highlighted in our previous Newsletter and we continue to do in this new release, the role of continuous ECGs is crucial to the assessment of drug-induced QT interval prolongation, and the intention of the FDA to have access to full 24-hour Holter ECGs represents a major step forward to investigate QT interval and drug interaction in a more meaningful manner. In this issue of the THEW Newsletter, we complete our review of methods to adress the dependency of QT interval to heart rate, hysteresis phenomenon and autonomic regulation. Drs. Halamek and Pueyo provide their expert opinion about methods developed to model the relationship between QT interval duration and the preceeding RR intervals. If QT adaption to HR and autonomic regulation of the cardiac ventricular repolarization seem to be the primary targets, the monitoring of cardiac arrhythmias in TQT is an additional item on the list of functionnalities described in the FDA request: "the tool shall be capable of providing identification of arrhythmias in long data and permit the reviewer to focus on these areas of a recording"[1]. Continuous monitoring of arrhythmias in TQT study represents an additional major step forward for the Agency. Finally and importantly, the access to continuous recordings enables the analysis of other dynamic aspects of the ECG such as T-wave alternans, heart rate variability and less clinically accepted ones, such as QT variability and heart rate turbulence, that are (among others) gaining credibility through independent clinical investigations. Yet, the upcoming challenge will reside primarily in the design of methods and tools allowing a fast and meaningful review by regulators (and sponsors) of all (or carefuly selected) cardiac beats from hundreds of thousands ones recorded in these safety studies.

To conclude, this is a very exciting time for individuals/organizations involved in quantitative electrocardiography and cardiac safety, the need for technologies pertaining to digital Holter analysis in drug studies will generate opportunities and novel incentives to improve current Holter methods, to define Holter standards, and of course to improve drug safety and efficacy.

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Also in this newsletter, we would like to welcome AstraZeneca who became a member of our initiative. This major pharmaceutical company has purchased the full membership for year 2010-2011and have gained access to all data currently hosted in our repository. Finally, we present a new IT manager of the THEW. John Wade has joined our team this Spring and he is involved in te dvelopment of the IT for the THEW. We hope you will enjoy this next issue.


A Dynamic model of QT/RR coupling by Josef Halamek, PhD(1), Pavel Jurák, PhD(1); Samuel J. Asirvatham, MD, FACC, FHRS(2)

1 Institute of Scientific Instruments - Brno, Czek Republic,2 Division of Cardiovascular Diseases, Department of Internal Medicine - Mayo Clinic, Rochester, Minnesota

Torsades de Pointes is a malignant arrhythmia associated with prolonged cardiac repolarization but is, however, frequently triggered by a sudden change in heart rate (RR interval)[1]. Thus, an ideal measurement of the QT interval should accommodate both QT dynamic, as well as static properties.  Ideally, a QT/RR model should have a minimal number of parameters and yet effectively describe the static and dynamic aspects of ventricular repolarization. In particular, the behavioral properties of QT interval occurring after a sudden change in heart rate. In this work, we describe a transfer function model of QT/RR coupling based on control system theory, tested and optimized on multiple abrupt RR interval changes (exercise, mental stress, and tilt table testing) [2-4].
The model QT (QTm) is given by the recursive relation among intervals

eq1

where qtxm and rrx are intervals with subtraction of mean levels QTxm=QTm-mean (QT), RRx=RR-mean (RR). Fitted parameters a1, b2, b3 are subject specific and are given by minimizing the residual between detected QT and QTm. An example of agreement is shown in Figure 1.

fig1

Fig 1. Effect of bicycle stress: 50 year-old-male healthy volunteer. a) Detected RR and QT intervals. b) The agreement between detected QT and computed QTm. c) QT as a function of RR; red marks are single beats; the continuous blue line is the running average of QT and RR over 40 beats; d) QT hysteresis elimination by the model. RRf is filtered RR, detailed description is in [3].

The QT interval response after an abrupt change of RR is called the QT step response and it is computed by fitting the model described above (a1, b2, b3). The QT parameters are determined from the step response described in Figure 2.  The suggested QT parameters includes:

  1. GainL: The gain of QT/RR coupling for slow variability of RR, i.e. the QT/RR slope, i.e. the amplitude of QT change that is achieved in steady state.
  2. GainF: The gain of QT/RR coupling for fast variability of RR, i.e. the amplitude of QT change immediately after the change of RR.
  3. The delay τ is the number of heartbeats after which the step response has achieved 90% of the change needed to attain the new steady state value.

fig2

Fig 2. The example of QT step response (for subject from Figure 1) and demonstration of QT parameters of physiological significance.  The step response (i.e. the behavior of QT after unit sudden change of RR) is computed from fitted parameters a1, b2, b3. Similar shapes of step responses were achieved over all analyzed measurements, and the shapes are in good agreement with previous measurements [5-7].

The full set of QT parameters is given by these parameters (GainL, GainF, τ) and by QTc and QT random variability computed from the model. The effect of the QT hysteresis is minimized by this model as shown in Figure 1 [3].

In conclusion, the advantages of the dynamic QT/RR model are:

  1. The QT static and dynamic properties are modeled.
  2. In comparison to other models, the residual between computed QTm and detected QT is minimized and the elimination of QT hysteresis is obtained [3, 4].
  3. The shape of the QT step response correlates well with prior measurements [5-7]. It should be emphasized that this shape is a result of analysis and no apriori assumption about the shape is used for the analysis. 

Technical requirements associated with dynamic QT/RR modeling:
A) Need for continuous long recordings:

  1. Significant RR excitation is needed (preferably more than 200 ms change), and a sufficient number of associated QT intervals must be detected. Hence, requirement for beat-to-beat QT is required. Similar need exists in the model based on exponential weighting of RR intervals [8, 9]. Consequently, these methods are dependent on the accurary of the QT measurement algorithm.
  2. The QT parameters are not only subject specific, but also excitation specific. Only excitation specificity may explain different triggers of QT arrhythmias[1], different QT behavior with different stress[10], and different QT/RR slope between different autonomic regulation.

Summary

The analysis of the dynamic and static properties of QT/RR relationship will help to better understand the QT physiology. Today drug cardiotoxicity is evaluated while neglecting both QT dynamic properties and excitation dependent QT coupling.  

It is well known that an abrupt change in the level of arousal or physical activity is a well-established trigger for malignant ventricular arrhythmia in patients with repolarization abnormalities [1]. We therefore hypothesized that significant differences in the QT interval during early excitation relative to the steady state may assist our understanding of why there is a higher prevalence of malignant arrhythmia in certain situations. Such dynamic differences of QT intervals are directly proportional to the level of the QT/RR slope and the time constant of QT adaptation, and indirectly proportional to the level of GainF.
The QT behavior on a sudden change of RR relative to steady state is demonstrated in Figure 3. The QT step response is given by the blue line, the QT steady state level by the black line. The QT difference is given by the red line, and corresponds to the dotted area between the step response and the steady state level of QT. The maximal amplitude of difference is seen at the time of RR change, and its level is (GainL - GainF )*ΔRR. The duration of QT difference depends on the time constant τ.  

fig3

Fig 3. The QT difference from steady state in sudden change of RR. The QT step response is blue line; the QT steady state level is the black line. The QT difference, given by delayed QT adaptation, is the red line; it corresponds to the dotted area between step response and steady state level.


The dynamic aspects of QT interval coupling is likely to describe the clinical behavior of cardiac repolarization during the onset and offset of excitation, which in turn may assist our understanding of why “Torsades de Pointes” initiates in some circumstances and not others despite comparable levels of activity or rest.  Furthermore, the testing of drug effects on QT dynamic parameters may elaborate why gender and certain specific physical states are more associated with drug-induced proarrhythmia. The proarrhytmic influence of drugs may originate in a change of GainL, GainF or τ without any change in QTc.

Access the list of references here.


QT/RR adaptation by Esther Pueyo, PhD

When evaluating QT intervals, knowledge about the underlying heart rate (HR) is required. While one possibility for QT analysis would be to select ECG episodes preceded by stable HR, this does not seem an adequate option, since relevant information for arrhythmic risk stratification can be found in episodes with marked HR changes. The QT/RR adaptation method provides a characterization of the QT interval adaptation dynamics in response to HR changes. Taking those dynamics into consideration, QT analysis can be extended to more general scenarios.

Until very recently, QT interval adaptation after a change in HR was mainly investigated in invasive studies, where the QT interval was shown to take at least two minutes to completely reach a new steady state after an abrupt change in pacing rate. In (1) a technique was proposed to quantify QT interval adaptation to spontaneous HR changes in Holter ECGs of post-myocardial infarction patients. That technique considers weighted averages of RR intervals preceding each QT measurement so as to account for the QT dependence on HR history. On average, the QT interval was found to require two and a half minutes to follow HR changes, although the initial tens of seconds to one minute were the most clinically relevant in the majority of cases. Both the duration and profile of QT adaptation were found to be highly individual. In agreement with results from invasive studies, the QT adaptation profile showed two distinct phases: a very fast initial adaptation followed by a second slower accommodation.  A measure of the time for QT adaptation was able to discriminate between patients at high and low risk of arrhythmic death, with a more prolonged adaptation related to increased risk.

The technique developed in (1) was later extended to account for possibly different QT adaptation characteristics along the ECG recording of one and the same subject (2). With that extended methodology, the time taken by the QT interval to follow HR changes was shown to range from just a few seconds in episodes of the ECG recording with little HR changes up to several minutes in episodes with large HR changes.

Characterization of QT/RR adaptation, as described above, was used to assess prophylactic treatment with amiodarone in survivors of acute myocardial infarction (3).  The QT/RR adaptation was found to be altered after chronic treatment with amiodarone, with different effects found in patients who survived and patients who suffered from arrhythmic death while on therapy. The observations derived in (3) suggest a potential use of indices derived from QT adaptation dynamics as markers for identification of patients who are not protected by the treatment with amiodarone. 

The ionic basis underlying QT/RR adaptation and its link to proarrhythmic mechanisms were investigated in (4). Computer simulations and experiments in human ventricular tissue were conducted, from which it was concluded that the QT interval follows similar adaptation dynamics to the action potential duration, in both cases consisting of a fast and a slow adaptation phases. While the fast phase is mainly driven by the calcium current kinetics, the slow accommodation is related to the accumulation of sodium within the cell. Increased risk of cardiac arrhythmias in patients with delayed rate adaptation could be a reflection of adverse ionic changes involving calcium and sodium dynamics that, upon further deterioration, may facilitate arrhythmia initiation via an increased likelihood of afterdepolarizations.

References available here.


PRESS RELEASE: AstraZeneca joins our Initiative to Further Cardiac Safety

growth

AstraZeneca purchased a one-year membership to gain access to an international repository of data designed to aid industry and academic researchers studying the electrical activity of the heart.  The database, called the Telemetric and Holter ECG Warehouse (THEW), helps researchers better evaluate how drugs affect the heart. Cardiac toxicity is one of the leading causes of removal of drugs from the market today, which is why ongoing research is needed to improve cardiac safety. 

THEW is the result of a partnership between the University of Rochester Medical Center, the U.S. Food and Drug Administration (FDA) and the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health. THEW consists of a digital catalogue of continuous electrocardiographic recordings from cardiac patients and healthy individuals, as well as electrocardiograms from safety studies implemented by major pharmaceutical companies. 

In addition to helping industry and academic researchers better understand the electrical activity of the heart and how individual drugs may influence this activity, the data may aid the development of new tools to more easily detect drugs that can have dangerous effects on the heart. With the THEW partnership, AstraZeneca will gain full access to a wide range of electrocardiogrpahic tracings and the associate clinical information that can be used to develop, implement and validate electrocardiographic markers of drug cardiotoxicity.

"We believe AstraZeneca's interest and involvement in this initiative is an important milestone. The support we have received from major pharmaceutical companies has grown over time and further support our decision to develop a repository for scientific data for the development of novel technologies related to cardiac safety," said Jean-Philippe Couderc, Ph.D., M.B.A, associate professor in the Division of Cardiology at the University of Rochester Medical Center and director of the THEW project. "We are hopeful that more pharmaceutical companies will see the value of the database and participate in this initiative as well, with the ultimate goal of improving patient safety and drug efficacy."

For more information about THEW membership visit here.


jcw

John C. Wade MS,
Senior Operations and Systems Analyst/Progammer Sr.

John is the newest member of our team, he is a native of Rochester (N.Y) and a graduate of Rochester Institute of Technology (RIT) and SUNY Empire State College. John holds a MS degree in Professional Studies from RIT (2008) and a BS in Computer Science (2004) from ESC. He came to the University of Rochester in Aug 2008 with extensive IT experience leveraged...... His primary role in the THEW organization is responsibility for all aspects of complex day to day technical management and entire systems support.