CDU Contributing Editor
SAN FRANCISCO, California The field of electrophysiology has changed dramatically over the past three decades, as the management of arrhythmias, or irregular heart rhythms, has evolved from simple pacemakers in the early 1970s to highly sophisticated implantable cardioverter defibrillators (ICDs) that can swiftly halt a sudden cardiac death episode, to biventricular pacers that provide significant relief from congestive heart failure. Catheter technology has likewise become far more sophisticated, providing a minimally invasive solution for the many elderly patients who suffer from atrial fibrillation (AF) and other, less-troublesome atrial arrhythmias.
With the availability of vastly better therapies, the need for improved diagnostic technologies has surged. At this year's meeting of the Heart Rhythm Society (HRS; Natick, Massachusetts) formerly known as the North American Society for Pacing and Electrophysiology there was considerable interest in this realm of EP, with several industry-sponsored evening seminars focused on emerging imaging technologies.
A session titled "Intracardiac Echocardiography for the Arrhythmia Specialist: Essentials and Advances," sponsored by EP MedSystems (West Berlin, New Jersey), tackled the subject of one of the newest and most exciting catheter-based techniques to benefit complex therapies. Intracardiac echocardiography (ICE) uses tiny catheters that provide real-time ultrasonic imaging from within the heart and the direct visualization of blood flow during minimally invasive procedures. The sensitivity of the catheter enables it to acquire high-quality, diagnostic images and Doppler blood flow information throughout the entire heart. Importantly, this diagnostic information about the entire heart's structure can be obtained from within the right side of the heart.
Several EP therapeutic applications are facilitated by ICE, with all of these procedures involving a trans-septal puncture to enable therapy to occur in the left side of the heart. Industry sources estimate that about 125,000 to 150,000 trans-septal procedures are performed annually, nearly all under X-ray angiography. The most important procedure using ICE today is pulmonary vein (PV) visualization, which guides the radiofrequency or cryothermic ablation of the tissue that is triggering AF. It is estimated that about 15,000 PV ablations will be performed this year in the U.S., with another 15,000 or more performed in international market. There is strong evidence from several clinical studies that ICE improves both the safety and efficacy of PV isolation and ablation relative to X-ray angiography.
Speaking to a packed room at the San Francisco Marriott, several EP physicians extolled the virtues of ICE. Mani Vannan, MD, professor of medicine at the University of California Medical Center (Irvine, California), who has performed more than 200 ICE procedures, praised ICE's ability to provide "real, real-time images" that other imaging modalities simply cannot provide. Jonathan Kalman, MD, professor of medicine at the Royal Melbourne Hospital (Melbourne, Australia), said that ICE guides him easily through the technically challenging trans-septal crossing, making several types of EP interventions possible and/or much easier. Kalman said that "ICE will play an increasing role in mapping and ablations in the future."
John Hummel, MD, an attending electrophysiologist from Riverside Memorial Hospital (Columbus, Ohio) and an avid ICE user, discussed a potential new and huge opportunity for the technique. About 30% of patients receiving a biventricular pacing device to resynchronize their ventricular rhythm and mitigate their congestive heart failure do not respond to this costly therapy. Hummel said he would shortly begin a pilot trial to answer the question of whether ICE can predict a patient's response to BVP therapy. His view is that more accurate BVP lead placement could improve BVP results for CHF patients.
At another symposium titled "Imaging in Electrophysiology: Present and Future Perspectives," David Wilber, MD, professor of cardiovascular sciences medicine at Loyola University Health Systems (Chicago, Illinois), cited several advantages of ICE vs. other imaging technologies, concluding that "there are lots of good reasons" to use intracardiac echocardiography.
Siemens Medical Solutions (Mountain View, California) currently dominates the ICE market, having initially gained FDA approval for its AcuNav catheter in December 1999. EP MedSystems is the only other player in the market, with FDA approval for its ViewMate system coming in September 2003.
The U.S. market for ICE procedures is still embryonic, with an estimated 4,000 to 5,000 procedures performed annually at a catheter price of $2,000 to $2,500 per case. More than half of these procedures are for pulmonary vein ablations, with other EP uses such as pacemaker or defibrillator lead placement or extraction guidance contributing as well. The most important cardiology application is for patent foramen ovale (PFO) closure procedures, where its utility and cost efficacy is high relative to other imaging modalities.
Another area where a diagnostic technology appears to have a very significant benefit is for the identification of patients who are at risk of sudden cardiac death. This area has surged in prominence in recent months, as landmark studies such as Multicenter Automatic Defibrillator Implantation Trial (MADIT-II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) have supported the wider use of very costly ICDs.
Consistent with MADIT-II results, the Centers for Medicare & Medicaid Services (CMS; Baltimore, Maryland), decided a year ago to include post-MI patients for reimbursement but failed to fully endorse the MADIT II criteria, instead limiting coverage to patients with an ejection fraction of 30% or less and a QRS duration (ventricular activity as shown in an electrocardiogram) of more than 120 milliseconds. This decision evoked significant opposition from clinicians, industry and medical associations, all of whom argued that the decision fell short of covering all patients known to be at risk. This furor continued throughout the HRS meeting.
With the release of favorable SCD-HeFT results at this year's American College of Cardiology (ACC; Bethesda, Maryland) annual scientific sessions in March, the heat has been turned up on CMS to determine which patients in the SCD-HeFT cohort should receive Medicare coverage, while attempting to control the spiraling costs of ICD implants (see sidebar, page 3).
A study on the accuracy of the QRS duration presented by Kenneth Stein, MD, an EP specialist from New York Presbyterian Hospital (New York) at this year's ACC meeting, concluded that "these data do not support the concept that a narrow QRS identifies a low-risk sub-population of MADIT-II type patients." MADIT-II patients have already suffered a heart attack and have an ejection fraction of less than 30%. Other studies of the utility of the QRS duration have demonstrated equivocal results, which has raised the level of debate even higher.
An interesting study presented at the meeting by Joseph Lin, MD, of the University of Minnesota (Minneapolis, Minnesota), showed that the cost of broader reimbursement parameters for ICDs may not be as expensive as initially proposed. He indicated that initial estimates of $12 billion for broad reimbursement were too high and that the cost could be from $2.5 billion to $5 billion. Lin said that while this is not an insignificant amount, "it is substantially less than what some people had been speculating."
Data first presented at the 2003 ACC meeting indicated that microvolt T-wave alternans (MTWA), a relatively simple, office-based diagnostic exam, might be the best approach for stratifying the population best suited to receive an ICD. At this year's HRS meeting, Daniel Bloomfield, MD, of the Columbia University College of Physicians and Surgeons (New York), reported that in a head-to-head comparison of MTWA and QRS duration in a MADIT-II population, T-wave alternans proved to be better than QRS at identifying not only a high-risk group, but also a low-risk group unlikely to benefit from an ICD. Specifically, the two-year mortality rate of patients identified to be high risk by MTWA was 18.9%, vs. 15% for QRS, while the two-year death rate for a negative MTWA was just 2.1% compared with 12.7% for QRS. "MTWA is clearly a stronger predictor of mortality than QRS in MADIT-II like patients and more importantly, the false negative rate of MTWA compared to QRS (1.8% vs. 7.6%) is an important benefit," Bloomfield said.
Cambridge Heart (Bedford, Massachusetts) developed the microvolt T-wave alternans test and has experienced excellent growth in the past two years. In addition to being part of the SCD-HeFT substudy, MTWA is currently being studied in two large, multi-center clinical trials the MASTER (Microvolt T-Wave Alternans Testing for Risk Stratification of Post MI Patients) study being sponsored by Medtronic (Minneapolis, Minnesota) and the ABCD (Alternans Before Cardioverter Defibrillator) study sponsored by St. Jude Medical (St. Paul, Minnesota).
The MASTER study will enroll 1,800 patients to evaluate MTWA in predicting which post-heart attack and low ejection fraction patients may be at greater near-term risk of an SCD episode and can therefore have the greatest benefit from ICD implantation. The ABCD trial is designed to evaluate and compare the positive predictive value of MTWA to an electrophysiology study in patients with ischemic heart disease, left ventricular dysfunction and non-sustained tachycardia. Patients undergo both the T-wave alternans test and EP study, receiving an ICD for either or both positive results. The incidence of a ventricular tachyarrhythmia event and total mortality will be evaluated for the duration of the study.
Study eyes SCD among young
Results of a new study reported at the HRS meeting indicate that most cases of sudden cardiac death (SCD) in young people are attributable to arrhythmias or structural problems in the coronary arteries. Lead researcher Robert Eckart, MD, a cardiologist at Brooke Army Medical Center (San Antonio, Texas) presented the findings during the HRS scientific sessions. Eckart and his four collaborating researchers studied the 127 sudden cardiac deaths that occurred among more than 6 million military recruits over the period 1977-2002. They found that arrhythmias and coronary artery anomalies were the leading causes of SCDs among the recruits who had suffered that fate.
Calling the finding "revolutionary," Eckart noted that conventional thinking has been that abnormal heart muscle thickening or hypertrophic cardiomyopathy has been the leading cause of sudden cardiac death among young athletes, for instance. In their detailed analysis of deaths by recruits in basic training, including autopsies, the researchers said that 40% of those who died from unexplained sudden cardiac death had experienced abnormal heart rhythms before dying. In addition, when compared to others with structurally normal hearts, there was a significant increase in pre-death heart damage indicated by myocardial fibrosis (scar-like tissue usually seen with prior tissue injury).
"These findings examine an area sudden cardiac death in military training that has largely been overlooked because of a lack of information," said Michael Cain, MD, president of the Heart Rhythm Society. "This investigation . . . has uncovered the critical need for more research to investigate the genetics behind these unexplained deaths and determine how we can better identify and prevent them. If there is a genetic link, we need to find it."
The study found hypertrophic cardiomyopathy to be in the stark minority of unknown causes. While echocardiography, with its ability to detect hypertrophic cardiomyopathy, had been thought to be an appropriate screening tool for SCD, these findings suggest that an echocardiogram does not exclude one of the most common causes of sudden death, and that the hearts of those studied would have appeared "normal" by that testing method.
Given the high association between a structurally normal heart and abnormal heart rhythms and heart damage, the Eckart group's data suggests that an electrocardiogram (EKG), which is significantly less costly, might be a more useful screening tool. Eckart said he now does an EKG and also looks for abnormalities in the coronary arteries. "By doing those two things, we are going to make a larger impact on sudden cardiac death in this population," he said.
While this study was performed in military recruits, Eckart said, "we feel the diverse ethnic background and enrollment without restriction to gender allows for this to be one of the most applicable reviews of its kind to young people throughout the nation."
Other studies presented at the HRS gathering indicated that older patients are as likely as younger people to benefit from implantable cardioverter defibrillators (ICDs) and catheter ablation for atrial fibrillation (AF). A study by physicians at Loyola University Medical Center (Maywood, Illinois) evaluated the results of catheter ablation in the elderly, with findings indicating that patients with AF being considered for catheter ablation should not be excluded on the basis of age alone. In a study of 174 patients, those over 65 years of age with paroxysmal or persistent atrial fibrillation had the same outcome with respect to procedural success and complications as younger patients undergoing AF catheter ablation.
The study was one of the first to look at outcome by age, which is important because the effects of AF increases with age.
A second study by physicians at St. Bartholomew's Hospital (London) examined 534 patients who underwent ICD implantation and found that age made no difference in survival rate. The researchers said survival of patients over 75 was identical to patients younger than 75.
"These age-related studies have significant clinical importance and will help to better diagnose and treat the growing number of patients the majority of whom are over the age of 65 with atrial fibrillation," said Cain. "It is critical that we not exclude patient populations if we have clinical evidence that they would benefit from life-saving therapies and procedures."
Boost for simulation by Medtronic
During the HRS conference, Medtronic announced a significant investment in simulation technologies and new facilities for the training of physicians and other clinical personnel. It said the training opportunities "enable beginning and seasoned cardiology specialists to enhance their device techniques in a highly sophisticated, risk-free, simulated medical setting."
Training is offered at various Medtronic Therapy and Procedure Training Centers using virtual reality imaging labs that provide realistic procedures and replicate patient cases in the areas of heart failure (cardiac resynchronization therapy), heart arrhythmias and coronary artery disease. However, HRS conference attendees were able to experience the latest in simulation technology in a visit to the Medtronic Therapy and Procedure Training Center Mobile Unit an 80-foot-long truck with two virtual cath labs that was part of Medtronic's exhibit hall space.
Based on a variety of cases with varying levels of difficulty, the training delivers both diagnostic and treatment challenges using virtual patients and virtual fluoroscopy with what Medtronic termed the "feel" of an actual case, but without risk. "As the industry leader in providing cardiac resynchronization therapy systems for the management of heart failure, our advanced simulation programs largely aim to accelerate safe physician use of this groundbreaking therapy," said Marshall Stanton, MD, vice president and medical director for Medtronic Cardiac Rhythm Management. "With our wide range of training programs and multitude of device and delivery system options, we are uniquely positioned to help physicians care for more heart failure patients with life-saving and life-enhancing medical technologies."
Randy Lieberman, MD, chair of the department of electrophysiology at Harper University Hospital (Detroit, Michigan) who participated in the development of the Medtronic simulator patient case studies and serves as program director for one of the company's Centers of Excellence for regional clinician training, said, "I have never seen a more cutting-edge and comprehensive approach to physician training." He added that the company's physician education programs for cardiac devices "will help make enormous strides in this area."
The Medtronic Therapy and Procedure Training Center-North America, opened last month in Minneapolis. It features a 120-person auditorium/classroom, four fully equipped operating rooms, virtual catheterization laboratories and simulator systems. Interactive satellite technology can transmit live procedures in real time from leading medical centers, allowing interaction with physicians performing new procedures. Medtronic Vascular training facilities in California, New York and Massachusetts focus on interventional cardiology procedures, giving physicians simulator-based training in the use of diagnostic techniques, angioplasty catheters, stents, distal protection systems and peripheral vascular procedures.
A Therapy and Procedure Training Center Mobile Unit, with a conference room and two virtual cath labs, will be based in Florida, and the company is establishing Therapy and Procedure Training Centers at Medtronic regional offices in New Jersey, California, Georgia, Colorado and Minnesota. Courses also will be offered at several regional hospitals and medical centers that have been selected as Medtronic Centers of Excellence.
Medtronic partnered with Immersion Medical (San Jose, California), a subsidiary of Immersion Corp., in developing its educational programs. The company said, "Immersion is the leading provider of haptic technology, which enables clinicians to experience how real procedures should feel so they can develop effective techniques before performing them on patients."
In an unrelated training announcement, Cain said the Heart Rhythm Society has approved and will soon be publishing guidelines for training for physicians who have "extensive experience" in pacemaker implantations who want to obtain the expertise to implant ICDs and cardiac resynchronization therapy (CRT) devices. Noting that several recent clinical studies have found that ICDs and CRT devices "can benefit a broader range of patients with serious heart disease," Cain said the HRS developed the guidelines "in part to address this growing need and at the same time to insure training competency by implanting physicians."
The guidelines include a formal training regimen for physicians not certified in electrophysiology to achieve competency to implant such devices and conduct patient follow-up. Cain said course work and objective assessment of mastery of the important concepts in such training "should meet the rigors required to satisfy CME [continuing medical education] criteria and must be approved by the society."
In addition to noting that such courses "should not be provided directly by industry," he added that physicians "must be proctored by an experienced and qualified, board-certified electrophysiologist for a minimum number of implants before working independently." The guidelines were approved by the HRS board earlier this year and are expected to be published in an upcoming issue of the society's journal, Heart Rhythm.
Also at the HRS meeting
A new analysis of the Defibrillators IN Acute Myocardial Infarction Trial (DINAMIT), sponsored by St. Jude Medical, found that in high-risk patients with recent acute myocardial infarction (MI), an ICD reduces arrhythmic death but not total mortality because of a marked increase in non-arrhythmic death. Patients who directly benefit from ICD therapy by receiving an appropriate shock experienced a greater rate of non-arrhythmic death than other ICD patients. Researchers said this suggests that preventing arrhythmic death after recent MI by the ICD may transform the mode of dying from arrhythmic to non-arrhythmic.
In the DINAMIT trial, 674 patients were randomized and followed for up to four years. All patients received a single chamber ICD in addition to patients with recent MI, left ventricular ejection fraction of less than or equal to 35%, and low rate variability receiving the best medical therapy.
A study presented at the meeting showed that flavonoids in green tea could contribute to a lower incidence of life-threatening ventricular arrhythmias in patients who have suffered a heart attack. The study was presented by researchers from the department of cardiology at the University of Heidelberg (Heidelberg, Germany), who examined the link between epigalloccatechin-3-gallate (EGCG) a type of flavonoid found in high concentrations in green tea on "human-ether-a-gogo-related gene" (HERG), a potassium channel shown to be present in a form of Long QT Syndrome, a human electrical system disorder that makes those who have it more susceptible to ventricular fibrillation.
Long QT Syndrome can be inherited, acquired after taking certain medications or caused by a combination of heredity and medications, the researchers noted. Flavonoids, which are contained in a large number of plant medicines, have anticarcinogenic, antioxidative, anti-inflammatory, antithrombotic, antibacterial and anti-allergic properties. Cain, the HRS president, referred to the taking of such flavonoids as "a preventive action that may be beneficial."
Commercially manufactured chest wall protectors may not adequately protect young athletes against chest wall injury, according to a study by physicians at the Tufts-New England Medical Center (Boston, Massachusetts) and the Minneapolis Heart Institute Foundation (Minneapolis, Minnesota). The researchers examined the dangers associated with commercially manufactured chest wall protectors for youth baseball. Seven commercially manufactured chest wall protectors including hard plastic-and-foam models were reviewed to assess the risk of sudden cardiac death resulting from chest wall impact during organized sports.
The results indicated that current chest wall protectors are ineffective in protecting youth athletes from chest wall blows, which can lead to SCD.
Another study by researchers at Children's Hospital (Boston, Massachusetts) showed that children with ICDs can safely participate in organized camp activities, including athletics, with the appropriate medical and nursing supervision. "Now children with ICDs have the option to participate in summer camp activities and can enjoy a summer filled with canoeing, archery and kickball at summer camp," said Maria Martuscello, RN, study co-author and organizer of the Pacemaker/AICD camp.
Over a four-year period, children between the ages of 7 and 18 with ICDs spent one weekend each summer participating in camp activities, including swimming, kayaking, soccer, basketball, rock climbing, and archery. All activities were supervised by experienced medical and nursing professionals. This was the first study of its kind, which included a population of 35 to 45 campers with significant structural and electrical heart disease.
The Circumferential Pulmonary Vein Ablation (CPVA) vs. Electrical Pulmonary Vein Isolation (EPVI) trial showed that both are equally effective in the treatment of paroxysmal or persistent atrial fibrillation a serious heart rhythm disorder where the heartbeat is irregular and rapid. CPVA was associated with a lower risk of PV stenosis and a left atrial flutter following an ablation procedure.
The society reported the launch of the Heart Rhythm Foundation, with Robert Hauser, MD, past president of NASPE which changed its name to the Heart Rhythm Society as of this year's 25th annual meeting as chairman of the board and Lisa Olson, PhD, as executive director.
"The Heart Rhythm Foundation is focused on developing programs to promote public awareness, physician education and patient advocacy for the prevention, diagnosis and treatment of cardiac arrhythmias," said Hauser. "Together with the society, the foundation will advocate awareness of and serve as the premier resource for heart rhythm disorders."
The foundation's first campaign will focus on raising awareness about sudden cardiac death, the leading cause of death in the U.S., through physician- and patient-directed educational programs. The organization also will conduct fundraising activities to support the efforts of both it and the society.
Speaking of funds, the Heart Rhythm Society reported that it had received the largest capital gifts in its 25-year history grants of $1 million each from Medtronic and the Guidant Foundation (Indianapolis, Indiana). Cain said the contributions "are bringing us closer to our goal of raising $6.5 million by 2004." He said the grants to the society's Capital Fund will be used to create a "global community to accelerate breakthroughs, expand educational opportunities, foster patient education and help the society serve as an advocate for patients."