The STAFF studies of the first 5 minutes of percutaneous coronary angioplasty balloon occlusion in man

    The STAFF Studies of the First 5 Minutes of Percutaneous Coronary Angioplasty Balloon Occlusion in Man Stafford Warren MD, FACC, Galen Wagner MD, FACC PII: DOI: Reference:

S0022-0736(14)00139-3 doi: 10.1016/j.jelectrocard.2014.04.011 YJELC 51857

To appear in:

Journal of Electrocardiology

Received date:

18 March 2014

Please cite this article as: Warren Stafford, Wagner Galen, The STAFF Studies of the First 5 Minutes of Percutaneous Coronary Angioplasty Balloon Occlusion in Man, Journal of Electrocardiology (2014), doi: 10.1016/j.jelectrocard.2014.04.011

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ACCEPTED MANUSCRIPT The STAFF Studies of the First 5 Minutes of Percutaneous Coronary Angioplasty Balloon Occlusion in Man

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Stafford Warren, MD, FACC Anne Arundel Medical Center Annapolis, MD

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Galen Wagner, MD, FACC Duke University Medical Center Durham, NC

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Address correspondence to:

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Stafford Warren, MD 888 Bestgate Rd., suite 215 Annapolis, MD, 21401 Tel 410-573-9805 Cell # 304-545-2889 Fax 410-573-9806 E-Mail: [email protected]

ACCEPTED MANUSCRIPT ABSTRACT The Staff Studies comprise a database of 228 patients undergoing elective five minute

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coronary artery balloon occlusion angioplasty at a single center in the pre-stent era in whom standard and high-frequency electrocardiographic and nuclear information was obtained

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immediately before, during and after balloon occlusion. The data was then analyzed by multiple

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investigators at different international academic centers from different perspectives.

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Simulating in a clinical setting the first five minutes of a heart attack, this database, now in digital format, is the largest database to date documenting standard and high-frequency ECG

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changes from the onset and for five minutes during acute coronary artery occlusion, with resting and occlusion imaging in a subset of these patients. The history, methodology, and legacy of

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these studies is discussed in this paper.

ACCEPTED MANUSCRIPT INTRODUCTION The STAFF Studies include a series of research projects based on clinical, angiographic,

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electrocardiographic (ECG) and nuclear imaging data acquired from patients receiving elective

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percutaneous coronary balloon angioplasty (PTCA) in the pre-stent era. Research utilizing this database has led to over 50 peer-reviewed, published manuscripts, 10 Doctoral Theses, and 12

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invitational international Symposia (the STAFF Symposia). The STAFF Studies data are

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uniquely clinically relevant because they document the first 5 minutes of complete coronary occlusion in man. Subsequently with the near universal use of stents replacing balloon

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angioplasty, inflation times are typically no more than 30 seconds. The STAFF Studies data were acquired at Charleston Area Medical Center during 1992-1996

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as presented in Table 1. The lead investigator, Stafford Warren, had initiated the use of a single

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prolonged balloon inflation rather than the typical series of brief inflations to achieve optimal angiographic and clinical results (1). During the late 1980’s, Warren had gradually increased the

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balloon inflation time from the typical 20-60 seconds up to the maximally clinically tolerated 5

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minutes. During these additional minutes of complete coronary occlusion, he observed on the ECG monitor that in addition to the expected ST-T repolarization changes, there were often remarkable depolarization changes represented by distortions of the QRS complexes. Both the repolarization and depolarization abnormalities disappeared within minutes following balloon deflation. Serial biochemical markers and ECG’s remained normal after the PTCA. In collaboration with Galen Wagner at Duke University Medical Center, a clinical research study was designed (STAFF 1). The study protocol included standard and high frequency ECG recordings acquired before, during and after PTCA. A Corazonix Predictor 1 (2) was used for the high frequency recordings.

ACCEPTED MANUSCRIPT Following the completion of the STAFF 1 study, there was a meeting of the investigators during the 1994 Computers in Cardiology meeting in Bethesda MD to review the results of this

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pilot study, and to plan for future STAFF studies. Several principles were identified: a dedicated

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study coordinator in Charleston, a non-ECG “gold standard” to quantify the acute ischemia, core labs for analyzing the individual data elements (e.g. standard ECGs), a monthly newsletter

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(STAFF Studies STAR), and biannual investigators meetings.

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The protocol for the second phase of these studies (STAFF II) included documentation of the location and extent of the acute transmural ischemia by radioisotope injection of technetium-

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labeled Sestamibi during the period of balloon occlusion (3). This experience guided the design of the final phase of these studies (STAFF III) in which a control Sestamibi study was also

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performed the day following the balloon occlusion. Recording of Standard 12 Lead ECG’s was

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replaced by continuous 12-lead ECG monitoring during the entire time in the catheterization laboratory using a Siemens-Elema (4) custom-made ECG recorder with a high sampling rate

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(1000 samples/second). The data from the 108 patients in the STAFF III database were compiled

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into a digital database that was stored and managed in the Lund University investigator site and made available to requesting investigators in other academic centers. Guidelines for STAFF Studies participation were drafted and a four member “STAFF Studies Steering Staff” (ST-4) was created, to provide leadership. Clinical and technical investigators were from academic centers in many countries: Sweden, France, Spain, The Netherlands, Israel, Portugal, Venezuela, Canada, and the United States. They analyzed the STAFF data from their unique perspectives, then shared ideas and collaborated through the STAFF symposia. These occurred typically every two years and were primarily in Europe as listed in Table 2.

ACCEPTED MANUSCRIPT In contrast with typical multicenter clinical trials that collect data from multiple centers for analysis and storage at a single center, the STAFF Studies collected data from a single center

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(Charleston, West Virginia) and analyzed these data at multiple centers. The standard ECG, high

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frequency ECG, and nuclear data were analyzed in dedicated Core Laboratories in Durham, NC, Oklahoma City, OK, and Rochester, MI respectively. The STAFF studies community functioned

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as a “University Without Walls”, in which collaboration among investigators located in

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multiple university centers and in the biomedical industry, and trained in multiple disciplines (cardiovascular clinicians, biomedical engineers, clinical physiologists, and medical and

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technical students) could learn from each other and achieve synergy. (5, 6)

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HISTORY

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Collaboration between cardiologists in practice and in academic centers has traditionally occurred through multicenter randomized controlled trials. The basis for the STAFF Studies

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model of an investigator-initiated study by a cardiologist in practice with the support of an

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academic research program had its roots in the Cardiology Fellowship Training Program at Duke University Medical Center. In the 1970’s, Cardiology Fellows at Duke were expected to explore the many unknown areas in cardiology, generate hypotheses, and test them with research projects. Initially daunting, the process became creative and exhilarating as meaningful clinical questions were asked and faculty mentoring and institutional support were made readily available through use of the newly developed “Duke Cardiovascular Databank.” This clinical and research resource that had been initially conceived by Eugene Stead in the 1960’s (7), prospectively registered and computer stored data on all patients with coronary artery disease (8) Collaboration between the current authors of this review began in this “academic cultural

ACCEPTED MANUSCRIPT incubator.” The myocardial specific Creatine Kinase isoenzyme (CK-MB), newly developed for clinical use at Duke (9) was observed by Warren to be transiently elevated following bypass

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surgery. This procedure included apical left ventricular venting, a common technique that was

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considered benign based on prior experience with cardiac valve surgery (10). To determine the cause of the rise in CK-MB, a consecutive series of patients identified in the Duke Databank

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were personally contacted by Warren to return to the Medical Center for recatheterization one

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year following the surgical procedure. The surprising discovery of a new apical wall-motion abnormality in many of these patients led to cessation of the apical venting technique in future

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patients.(11)

Ongoing collaboration between graduated Fellows and researchers at Duke was encouraged

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and Wagner was instrumental in developing the Duke Cardiology Fellows Society, enabling

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maintenance of connections with the Duke Cardiology faculty and with each other (12). The Duke Cardiology Fellows Society developed into the Duke University Cooperative

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Cardiovascular Society (DUCCS), to more formally link these individuals through collaborative

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research projects (13)

With this background, it was logical for Warren to contact one of his Duke Cardiology Fellowship mentors, Galen Wagner for collaboration in the design of a clinical research study to determine the significance of the complex transient ECG changes during complete coronary PTCA balloon occlusion. Wagner used his experience with the Duke Cardiovascular Databank and with observations of both standard and high-frequency ECG changes in the early minutes of acute myocardial ischemia/infarction to assist Warren in the design of the STAFF Studies.

ACCEPTED MANUSCRIPT Shimon Abboud of Belinson University in Tel Aviv, during his PhD studies at Massachusetts Institute of Technology, had compared standard and high-frequency ECG changes

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during both experimental and clinical acute coronary occlusion. The high-frequency ECG’s

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provided unique quantitative information regarding the pathophysiology of acute depolarization and repolarization changes (14, 15). A Duke-trained MD/Ph.D., David Albert had developed

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recording equipment for both standard and high-frequency ECG recording in his Corazonix

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Company (2), and made his device available to Wagner and Duke Electrophysiology Chief Eric Prystowski for pilot studies. Albert also provided the recording device for Warren to use for the

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STAFF I and II Studies at Charleston Area Medical Center.

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The novel idea of employing a longer balloon inflation to achieve a better angiographic

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clinical result was first reported by Bittar and Warren from Charleston, W.V. in 1991 in Clinical Research (1). At that time the United States was still two years away from having FDA-

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approved coronary stents. In that report it was found that a five minute inflation could be

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tolerated in 100% of circumflex, 95% of right, and 86% of left anterior descending coronary arteries. The benefits of a single prolonged balloon inflation were a slightly larger coronary lumen and fewer visible intimal dissections. Complete occlusion of a coronary artery from a PTCA balloon simulated the abrupt onset of symptoms due to total thrombotic coronary occlusion found in patients with ST elevation acute myocardial infarctions (STEMI’s) and (for some patients) non-ST elevation acute myocardial infarctions (NSTEMI’s). This similarity provided the opportunity to study the ECG changes in the first few minutes of a coronary occlusion. The Corazonix Predictor I recording equipment (Oklahoma City, Ok) was the only ECG recorder at that time that would record high-frequency information, 0.05-300 Hz, rather

ACCEPTED MANUSCRIPT than the more limited 0.05-100 Hz in a standard ECG machine. Using the Corazonix ECG recorder, 63 patients were enrolled in a pilot study (STAFF I) with a part-time nursing

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coordinator (who obtained informed consent, applied electrodes and obtained and store ECG’s )

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to determine feasibility of data collection in this manner. Two logistical issues became apparent. The electrodes would need to be transparent for adequate fluoroscopic visualization and a full-

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time study coordinator was required to assure that a common protocol was followed for

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consecutive patients. STAFF II was begun with fluoroscopically transparent electrodes and a full-time study coordinator, Gary Hartman, who was available for all procedures. Fifty-three

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patients were enrolled, and a Sestamibi radioisotope injection was administered in the catheterization laboratory during balloon occlusion to evaluate extent and location of myocardial

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ischemia. Feasibility of consistently collecting quantitative ECG and scintigraphic data had now

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been clearly established.

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To further study the electrical phenomena occurring in the first 5 min of coronary balloon

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occlusion, STAFF III was initiated with a 4th year medical student, Michael Ringborn, from Lund University in Lund, Sweden as study coordinator, enrolling 108 patients over a 6 month period. A pre-inflation ECG was acquired continuously for 5 minutes in the catheterization laboratory with the patient resting in the supine position, before any catheter insertion. A second ECG recording was initiated 1 minute before balloon inflation occurred and continued until 4 minutes after balloon inflation had been completed. This was done using a Siemens-Elema machine that recorded and stored 12-lead ECG signals digitized at a sampling frequency of 1000 Hz. with an amplitude resolution of 0.6 micro-V. To better understand the distribution and extent of myocardial involvement and correlate that with the ECG changes, and after informed

ACCEPTED MANUSCRIPT consent, 99mTC- Sestamibi was given to 35 of these patients one minute after balloon occlusion with subsequent imaging shortly thereafter as well as imaging done the following day as a

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control. .

An additional hurdle along the way included the time required to submit and obtain IRS

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approval for the modified protocol (6 weeks). The cost of the project was shared by DUCCS,

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CAMC, the Charleston Cardiology Research Foundation, and the Lund University Biomedical Lab (analyzing HF-QRS). The coordination of the project was shared among lead investigators at

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the Charleston Area Medical Center and at Lund and Duke University Medical Centers. A STAFF Studies newsletter, The Staff Studies STAR, was published through DUCCS to provide

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bimonthly progress reports by the research coordinator for distribution to all STAFF

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investigators.

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The STAFF III database, collected during 1995-96 was provided to researchers at technical

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academic centers for analysis in specific projects. In 1997 the first STAFF Symposium was held in Lund, Sweden for the investigators to come together to share insights and analysis results. Now, coming up to the 12th Staff Symposium in Boston this September and 16 years later (Table 2), the shared communication during these Symposia have expanded the research topics to include related cardiovascular challenges , but their format has remained constant. Investigators using STAFF data are invited to present to their colleagues in a “round table” configuration to facilitate interactive discussion. Participating STAFF investigators volunteer to host these research meetings.

An important addition during the 4th STAFF Symposium in 2001 was the

addition of a Young Investigators Award, named the Michael Ringborn Award, for the student

ACCEPTED MANUSCRIPT investigator who coordinated the STAFF III Study five years previously. This award is now presented annually to a young investigator, on the basis of the creativity of the research and the

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clarity of the presentation. This recognition has reinforced one of the shared goals of the STAFF

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investigators; to mentor young researchers and to reward their efforts while providing constructive feedback from different perspectives.

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Several key elements of the STAFF Symposia have evolved during these almost 20-year

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experiences:

1. Having a limited number of invited participants (30-40).

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2. Scheduling the symposia to precede or follow (in a nearby location) Computing in Cardiology symposia in which many of the STAFF investigators participate.

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3. Conducting the symposia in smaller hotel, non-urban settings where participants can share

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meals and socialize easily without urban distractions. 4. Inviting and mentoring young investigators and maintaining the Young Investigator Award.

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industry.

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5. Including participants with technical and clinical experience, from both academia and

6. Having administrative support for the STAFF Symposia; provided by Kathy Shuping and Galen Wagner through DUCCS.

LEGACY 1. International multi-center research programs built around single center databases

The STAFF Studies provides a model of an international multi-center research program built around the single center database from Charleston WV. The central idea has been to approach different aspects of a clinical/diagnostic problem using a common data set. The results of the

ACCEPTED MANUSCRIPT individual studies are directly comparable, and therefore, provide multiple complementary views on the same problem. An additional benefit has been the high ratio between the number of

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publications and the effort related to the data collection.

In addition to the papers published and PhD’s awarded based on analysis and collaboration

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throughout the STAFF Studies, they have advanced medical knowledge about the standard and

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high-frequency electrocardiographic changes correlated with nuclear imaging that are likely to occur in the first 5 minutes of a heart attack in man and the variable ECG changes resulting from

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myocardial ischemia. Discussions during the serial STAFF Symposia have formulated plans for related studies using the format of a single center database for facilitation of widespread projects.

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During the 5th STAFF Symposia in 2003 the basis for determining the added value of high

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frequency ECG during the demand ischemia of exercise stress testing was considered. This led to a study in 2004 in Charleston, WV, directed by Staff Warren and coordinated by Jonathan

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Lipton, a recent medical graduate of Leiden University. It evaluated continuous standard 12-

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Lead and high-frequency recordings during dual isotope (99mTc-Sestamibi/201Thallium) treadmill exercise testing in 133 consecutive patients with known or suspected ischemic heart disease. The goal was to evaluate waveform changes due to subendocardial ischemia of acutely increased myocardial demand (16) Biologic Signal Processing Ltd (BSP), an early participant in the STAFF Studies and founded by Amir Becker in 2000, analyzed these data and incorporated the high-frequency QRS information into their HyperQ ™ monitoring system for the detection of ischemic heart disease. A study by Toledo et al further evaluated the contribution of high frequency changes during demand ischemia for clinical stress testing (17). Schiller AG has

ACCEPTED MANUSCRIPT adopted the HyperQ method and is now offering 12-lead stress ECG and resting ECG systems

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with the additional capability to analyze high-frequency components of the ECG signal.

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The emergence of Cardiac Magnetic Resonance (CMR) technology as a clinical modality for localizing and quantifying myocardial scar led members of the STAFF program to develop a

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method for assembling a collaborative research team from multiple disciplines and academic

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centers to study the relationships between ECG estimation and MRI measurement of myocardial infarct size, as reported by Engblom et al in 2001 (18). STAFF Studies leaders worked with

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Henry Dargie at the University of Glasgow’s Western Infirmary to develop a single center database of patients with acute coronary syndromes. Dr Dargie’s young investigator, Thomas

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Martin coordinated a study of the relationship between the serial ECG and CMR changes during

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one year follow-up. Consecutive patients were entered into a protocol for immediate and serial Magnetic resonance and Electrocardiographic Technologies studies (MALT), that evolved into

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another international research program. The study was designed and data acquisition begun in

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2002 (19). The 1st MALT Symposium was convened in Glasgow in 2003, following the STAFF Symposia format. These symposia have continued annually in Scotland, England, Sweden, Denmark, Slovakia, and the Netherlands, and the 12th MALT meeting is in Noordwijk, the Netherlands in 2014. There has been about 20% overlap between STAFF and MALT Investigators.

2. International Scientific Summer Schools

The development of young investigators has been a goal of the STAFF symposia through the Young Investigator Michael Ringborn Award, now having been awarded to 8 young

ACCEPTED MANUSCRIPT investigators (Table 2). The roundtable-style discussion from collaborative multidisciplinary perspectives of all papers presented has provided critical feedback for subsequent research

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projects.

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The senior STAFF and MALT investigators have used these studies as training grounds for mentoring young investigators from the participating University medical centers, as a

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complementary “University Without Walls.” During the 1990’s Galen Wagner and Eric

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Eisenstein developed an “Outcomes Research Practicum” in the Duke Clinical Research Institute to mentor young investigators The outcomes of their initial implementation of this series of four

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workshops at Duke, and in the DUCCS and STAFF programs, were reported in 2006 (20). These workshops were then adapted into an International Scientific Summer School (ISSS)

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program in Central and Eastern Europe, organized by Ljuba Bacharova. Health care and

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biomedical technical trainees work collaboratively on research projects of their choosing with faculty facilitation as another aspect of a “University Without Walls.” (21- 26). There have now

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Romania.

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been 11 ISSS Workshops provided in Slovakia, Turkey, Poland, Macedonia, Croatia, and

3. International research mentoring International research mentoring is an opportunity to promote research and research education across borders Several phenomena have taken place over the last century that have laid the foundation for collaboration and mentoring internationally: rapid transit by plane, rail, and car; opening of national borders; development of the facsimile followed by the internet for rapid data transmission; audio and video conferencing for direct communication; and finally the use of a common scientific language (English). A systematic approach to research can be taught

ACCEPTED MANUSCRIPT with science as its unifying language. International research mentoring was the focus of a discussion led by Hakan Arheden of Lund Uuniversity during the 10th MALT meeting in 2012

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in Casta-Papiernicka, Slovakia. This discussion was divided into three parts: What is it? So

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what? and Now what? The meaning of the word “mentoring” was considered. Is “mentoring” distinct from ”coaching” or “supervision”? A young investigator commented:” International

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research mentoring is the process by which senior scientists facilitate junior scientists to leave

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their local comfort zones and reach for their goals by working with senior scientists located at other centers., whether or not they travel to meet in person or use electronic means of direct

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communication.” Mentoring, coaching, and supervising are three different but related processes that can all play a role in successfully leading young researchers to achieve their goals.

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International mentoring creates a wider platform and perspective than might be achieved locally,

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and the mentor may well benefit from this wider platform as does the student. For research presentations by junior researchers at international meetings, a format that uses dialogue to

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improve projects has been viewed as more successful than the more traditional criticizing and

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defending approach. A smaller group and round-table format help facilitate this more constructive approach.

4. Publications - Multidisciplinary, Multimodal The limited-participant, invitational, multi-disciplinary symposium format with a focused agenda has fostered trust and collegial sharing that has helped enable members of the STAFF Symposia steering committee, Leif Sornmo from Sweden and Pablo Laguna from Spain to coauthor a textbook, Bioelectrical Signal Processing in Cardiac and Neurological Conditions in 2005 (27), and Olle Pahlm from Sweden and Galen Wagner from the Unites States to co-author the book, Cardiovascular Multimodal Imaging Diagnosis and Therapy in 2011. (28). Many of the

ACCEPTED MANUSCRIPT publications based on analysis of the STAFF database have involved collaboration between investigators who met through the Symposia and discussed research ideas that led to subsequent

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publications. A partial list of these are referenced at the end of the article by Laguna and Sornmo

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in this July issue of the Journal of Electrocardiology.

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REFERENCES:

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1. Bittar G, Warren SG. The effect of prolonged balloon inflation on the immediate results of

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percutaneous transluminal coronary angioplasty (PTCA) using conventional balloon catheters. Clinical Research. 1992:40, #2, 362 A.

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2. Pettersson J. Warren SG, Mehta N, Lander P, Berberi EJ, Gates K, Sornmo L, Selvester RH, Wagner GS; Changes in Standard and high frequency electrocardiography during five minute

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coronary artery occlusion in man. J Electrocard 28 Supp:225-227,1995

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3. Persson,E, Palmer,J, Petterson,J, et al. Quantification of myocardial hypoperfusion with 99m Tc-sestamibi in patients undergoing prolonged coronary artery balloon occlusion. Nucl Med

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Commun.2002; 23:219.

4. Ringborn M, Pettersson J, Persson E, Warren SG, Platanov P, Pahlm O, Wagner GS.

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Comparison of high frequency QRS components and ST-segment elevation to detect and

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quantify acute myocardial ischemia. J Electrocardiol 2010:43;113-120. 5. Wagner GS, Engblom H, Billgren T, Carlson M, Hedstrom E, Ugander M, Kasper J, Selvester

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RH, Arheden H, Eisenstein E, Kasper J, White R. A method for assembling a collaborative research team from multiple disciplines and academic centers to study the relationships between ECG estimation and MRI measurement of myocardial infarct size. JECG 34 Supp 1-6, 2001. 6. Wagner GS, Engblom H, Billgren T, Carlson M, Hedstrom E, Ugander M, Kasper J, Selvester RH, Arheden H, Eisenstein E, Kasper J, White R. A method for assembling a collaborative research team from multiple disciplines and academic centers to study the relationships between ECG estimation and MRI measurement of myocardial infarct size. JECG 34 Supp 1-6, 2001. 7. Wagner GS, Cebe B, Rozear MP, editors. E. A. Stead, Jr.: What This Patient Needs is a Doctor. Durham, Carolina Academic Press, 1978.

ACCEPTED MANUSCRIPT 8. Wagner GS, Rosati RA, Mittler BS, Lee KL. A computerized textbook for determining optimal management of patients with coronary artery disease. Second Henry Ford Hospital

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International Symposium on Cardiac Surgery, edited by Davila JC. New York, Appleton-

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Century-Crofts, 1977, pp 625-631.

9. Wagner GS, Roe CR, Limbird LE, Rosati RA, Wallace AG. The importance of identification

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of the myocardial-specific isoenzyme of creatine phosphokinase (MB form) in the diagnosis of

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acute myocardial infarction. Circulation 47:263-269, 1973.

10. Shaw RA, Kong Y, Pritchett ELC, Warren SG, Oldham HN, Wagner GS. Ventricular apical

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vents and postoperative focal contraction abnormalities in patients undergoing coronary artery bypass surgery. Circulation 55:434-438, 1977.

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11. Warren SG, Wagner GS, Bethea CF, Roe CR, Oldham HN, Kong Y. Diagnostic and

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prognostic significance of electrocardiographic and CPK isoenzyme changes following coronary bypass surgery: correlation with findings at one year. AHJ 93:189-196, 1977.

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12. Pritchett ELC, Wagner GS, Wallace AG, Greenfield JC Jr. Career Choices of 135

1986.

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Cardiology Trainees at Duke University Medical Center from 1970 to 1984. AJC 57:313-315,

13. Davidson RM, McNeer F, Logan L, Higginbotham MB, Lin C, Wagner GS; A Cooperative Network of Trained Sites for the Conduct of a Complex Clinical trial: A New Concept in Multicenter Clinical Research. AHJ 151:451-456, 2006.

14. Warren SG, Wagner GS, Bethea CF, Roe CR, Oldham HN, Kong Y. Diagnostic and prognostic significance of electrocardiographic and CPK isoenzyme changes following coronary bypass surgery: correlation with findings at one year. AHJ 93:189-196, 197S

ACCEPTED MANUSCRIPT 15. Abboud S, Cohen RJ, Selwyn A, Ganz P, Sadeh D, Friedman PL. Detection of transient myocardial ischemia by computer analysis of standard and hi-frequency ECGs in patients

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undergoing percutaneous transluminal coronary angioplasty. Circulation 1987:76:585.

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16. Lipton JA, Warren SG, Broce M, Abboud S, Beker A, Sornmo L, Lilly DR, Maynard CC, Lucas DB, Wagner GS; High frequency QRS electrocardiogram analysis during exercise stress

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testing for detecting ischemia. Int J Cardiol. 2008:29;124(2):198-203.

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17. Toledo E, Lipton JA, Warren SG, Abboud S, Broce M, Lilly DR, Maynard C, Lucas BD, Wagner GS, Detection of Stress-Induced Myocardial Ischemia from the depolarization phase of the cardiac cycle

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– a preliminary study. J Electrocardiol 2009:42:240-247.

18. Wagner GS, Engblom H, Billgren T, Carlson M, Hedstrom E, Ugander M, Kasper J,

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Selvester RH, Arheden H, Eisenstein E, Kasper J, White R. A method for assembling a

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collaborative research team from multiple disciplines and academic centers to study the

34 Supp 1-6, 2001.

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relationships between ECG estimation and MRI measurement of myocardial infarct size. JECG

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19. Martin TN, Groenning BA, Steedman T, Foster JE, Eliot AT, Dargie HJ, Selvester RH, Pahlm O, Wagner GS; ST-segment deviation analysis of the admission 12-lead electrocardiogram as an aid to early diagnosis of acute myocardial infarction with a cardiac magnetic resonance imaging gold standard. (MALT 5) J Am Coll Cardiol. 2007 50(11):1021-8. 20. Davis TH, III, Wagner GS, Gleim G, Andolsek KM, Arheden H, Austin R et al. (2006) Problem-based learning of research skills. J Electrocardiol; 39, pp.120-128. 21. Bacharova L, Wagner G, Misak A. (2006) The Scientific Summer School in Slovakia, Liptovsky Jan, June 20-25, 2006. J Electrocardiol; 39, pp. 437-439.

ACCEPTED MANUSCRIPT 22. Bacharova L, Kirchnerova J. (2008) Continuous international network building to promote scientific publication: Scientific Summer School, Pezinok, Slovakia, May 25-30, 2008. Anadolu

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Kardiyol Derg; 8, pp. 319-321.

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23. Misak A, Bacharova L. (2008) The Early Role of Scientific Journals in Supporting Young Scientists to Become Independent Researchers; Report on Scientific Summer Schools held in

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Slovakia and Macedonia in 2008. J Electrocardiol; 41, pp. 448-449.

Croatia. J Electrocardiol 2009; 42: 471-472.

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24. Skrak P, Maricic S: “Train the Trainers” Scientific Summer School, June 15-19, 2009, Trilj,

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25. Hugo V: 2009 Scientific Summer School, Poland. J Electrocardiol 2009; 42: 700. Bacharova L, Hakacova N: Building network for enhancement of scientific/research literacy:

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Kardiyol Derg 2009; 9: 433-434.

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The Scientific Summer School 2009 in Szczepanow, Poland. Anatolian J Cardiol/ Anadolu

26. Hakacova N, Baysan O, Bell SJ: Problem-oriented education and cross-cultural

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collaboration: experiences and comments on the Scientific Summer School in Turkey. Anatolian

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J Cardiol/ Anadolu Kardiyol Derg2010; 10: 388-389.. 27. Sornmo L, Laguna P. Bioelectrical Signal Processing in Cardiac and Neurological Conditions Elsevier, 2005. 28. Pahlm O, Wagner GS – editors: Cardiovascular Multi-Modal Imaging Diagnosis and Therapy. McGraw-Hill 2011.

ACCEPTED MANUSCRIPT TABLE 1 STAFF STUDIES COORDINATOR

YEARS

# PATIENTS

STANDARD ECG

HIGH FREQUENCY ECG

S

I

Part-time RN

1992 - 93

63

Standard 12-lead - paper

3 orthogonal leads

n

II

Gary Hartman

1994 - 95

53

3 orthogonal leads

n

III

Michael Ringborn

1995 - 96

108

Standard 12-lead - paper Continuous 12-lead electronic

12 standard leads

o

CITY

COUNTRY

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YEAR 1997

LUND

2

1999

BRAUNLAGE

3

2001

NOORDWIJK

4

2002

WAGININGEN

5

2003

PEREA

6

2005

PIZAY

7

2006

8

2007

9

2008

10

2010

11

2012

# PARTICIPANTS

RINGBORN YIA

SWEDEN

19

none

GERMANY

32

none

NETHERLANDS

14

none

NETHERLANDS

26

Elin Tragardh

GREECE

34

Esther Pueyo

FRANCE

36

Jonathan Lipton

ALBARRACIN

SPAIN

30

Henrik Engblom

WRIGHTSVILLE BEACH

USA

35

Ganesh Murtha

BERTINORO

ITALY

36

Sonia Gouveia

PORTRUSH

N IRELAND

35

Peter Scott

PASZKOWSKA

POLAND

46

Cato ter Haar

CE

PT

ED

MA

1

AC

RI P

SC

TABLE 2 STAFF SYMPOSIA

SYMPOSIA

T

STUDY #s