By AARON LORENZO
and HOLLAND JOHNSON
ATLANTA, Georgia – Defibrillator therapy received several ringing endorsements as a number of clinical trials whose results were presented during last month's American College of Cardiology (ACC; Bethesda, Maryland) annual scientific sessions pointed toward positive usage of the devices .
Both internal and external defibrillators earned high marks, suggesting the systems' broad applicability will lead to their continued acceptance both inside and outside the health care community. "Time is of the essence – electricity saves lives, and I think that's really what we've heard today," said Douglas Zipes, MD, president of the ACC and moderator of a press conference on defibrillators held following a late-breaking clinical trials session at the Georgia World Congress Center.
Among the most promising were the results of the MADIT II study, a 1,232-patient trial investigating, for patients with a prior heart disease history, the preventive value of the Contak CD implantable cardioverter defibrillator (ICD) manufactured by Guidant (Indianapolis, Indiana). The results of the four-year study showed the ICD reduced the death rate by 31%. "There was a highly significant improvement in survival and reduction in mortality," said Arthur Moss, MD, of the University of Rochester Medical Center (Rochester, New York), the trial's principal investigator. "The ICD group had at three years a 78% survival, while the non-ICD group had a 69% survival rate." Moss identified the difference between the numbers as the amount of life in years saved. "That's quite considerable and highly significant," he said. "It didn't happen by chance alone." He also reported two-year follow-up numbers that resulted in 19.8% mortality in the conventional group, a percentage improved to 14.2% mortality in the defibrillator group.
"The hazard rate tells you that there is a 31% reduction in mortality at any interval in time – one day, one month, one year, four years," Moss said. "Equally important to reduction in mortality are results that improved survival is on top of optimal medical management."
The InSync ICD, manufactured by Medtronic (Minneapolis, Minnesota), also gained attention during the ACC sessions. Medtronic currently sells the InSync biventricular pacemaker for congestive heart failure. With the InSync ICD, an implantable defibrillator is added to the pacemaker technology.
"Patients with the biventricular system on, in addition to the ICD, had continuous improvement in their quality of life over the six-month period," said James Young, MD, of the Cleveland Clinic Foundation (Cleveland, Ohio). "In a clinical composite response, an overall local response indicating how well patients do, there again was a statistically significant improvement in those individuals in the active therapeutic group. And finally, as we look at a combined morbidity/mortality index, hospitalizations for heart failure with mortality, we see a non-statistically significant trend in favor of the treatment group." The bottom line, Young said, "is [that] biventricular pacing therapies are effective when combined with ICD therapies – they improve quality of life and they do not impede the normal functions of ICD arrhythmia detection."
Earlier in March, the Circulatory System Devices Panel of the FDA's Medical Devices Advisory Committee recommended by a 6-to-5 vote the InSync Model 7272 ICD System for patients with heart failure and ventricular conduction delays.
While the news regarding the implantable devices was welcome news for that particular segment of the defibrillation market, three other clinicians presented positive findings of trials involving more visible defibrillators. The LifeVest wearable defibrillator, developed by LifeCor (Pittsburgh, Pennsylvania), was the subject of a three-year study to protect patients temporarily at risk for sudden cardiac arrest, but not eligible for an implantable ICD. In the two-arm trial, the product saved six lives, with a low incidence of false shocks – just 2.3%.
"The wearable defibrillator, based on the results of this trial, can detect and treat ventricular tachyrhythmia in patients at high risk for sudden cardiac death," said Arthur Feldman, MD, of the University of Pittsburgh School of Medicine (Pittsburgh, Pennsylvania). "It might preclude the expense and risk of an ICD in patients who have a defined window of risk for sudden cardiac death. And it may be very helpful in identifying patients at risk for subsequent lethal events in the short term."
The public also appears keen on usage of defibrillators, according to both an Italian study and a trial involving American Airlines (Fort Worth, Texas) flight attendants. Each of the airline's 20,000 flight attendants undergoes 4 1/2 hours of training with an automatic external defibrillator (AED), along with annual 90-minute re-training sessions. Data showed that 94% of those surveyed reacted positively to their training, and also pointed toward a public willingness to learn to operate the external systems. "AED training was overall deemed to be adequate by the vast majority of flight attendants," said Theodore Takata, MD, of the University of Texas Southwestern Medical Center (Dallas, Texas) and American Airlines. "We anticipate that the general assistance from bystander volunteers will improve as AEDs become more familiar to the general public, and as these devices become more widely available."
The Italian study, labeled the Piacenza Progetto Vita Experience, resulted in similar findings. In the trial, numerous AEDs were installed in various public places – such as post offices and train stations – in the city of Piacenza. Lay volunteers were recruited and trained in operating the devices, with follow-up results showing considerable improvement in patient outcomes. The study found that survival rate more than doubles if a first responder uses an AED before emergency medical personnel are able to arrive on the scene, with percentages improving from 18% to 41%. These studies indicate numerous positives for defibrillator technology in various settings, meaning – as the ultimate endpoint – more lives saved.
BNP effective CHF predictor in the ER
One of the most notable studies presented during this year's ACC gathering in terms of sheer volume potential was the 1,586-patient Breathing Not Properly (BNP) Trial, a seven-site multinational study. The trial looked at how a protein called B-type natriuretic peptide (also BNP) can be used as a diagnostic predictor of CHF in patients suffering from dypsnea or shortness of breath, a symptom that accounts for million of emergency room visits each year. BNP is a naturally occurring hormone in the body that aids healthy functioning of the heart, and is secreted by the ventricles as one of the body's natural responses to heart failure. Presenting the data from the BNP Trial were Peter McCullough, MD, chief of cardiology at the University of Missouri-Kansas City School of Medicine (Kansas City, Missouri) and Alan Maisel, MD, director of the coronary care unit at the San Diego Veterans Affairs Healthcare System (San Diego, California).
"In the study, BNP was the single most accurate predictor of congestive heart failure," McCullough said. "BNP performed better than both the NHANES [National Health and Nutrition and Examination Survey] and the Framingham criteria, arguably the most accepted definition for CHF." The study findings showed that an optimal dose of 100pg/ml BNP correctly diagnosed CHF 81% of the time, compared to 67% for NHANES and 73% for the Framingham protocol.
The BNP study used the Triage BNP Test developed by Biosite (San Diego, California). In 15 minutes, the test evaluates all the circulating levels of BNP in both symptomatic (late-stage) and asymptomatic (early-stage) CHF patients. It is the only test currently approved by the FDA in the diagnosis of CHF. Importantly, Maisel noted that physician clinical diagnostic indecision levels fell 74% (from 43% to 11%) when a BNP test was used to diagnose CHF. "The implication of all this is that the [U.S.] heart guidelines should incorporate BNP in the clinical diagnosis of heart failure." He said the time has come, noting that BNP testing is already used extensively in Europe and is part of their guidelines.
At a press conference on BNP and blood markers held following the late-breaking trials session at which the trial results were presented, McCullough said the test could benefit "tens of millions of patients in the U.S. alone" who present with breathing problems in emergency rooms. Maisel said that the price of $20 to $25 dollars per test is negligible, especially "when you consider the cost of an emergency room visit is around $10,000 and the price of an echocardiogram is almost $1,000." He said that the test already is being used in over 500 hospitals in this country out of an estimated total of 6,000. "We've been using it at our hospital since it was approved by the FDA" in November 2000. He said that besides emergency department physicians, cardiologists, internal medicine specialists and family practitioners also are using the test in their practices.
On the exhibit floor
Toshiba America Medical Systems (TAMS; Tustin, California) highlighted the Aquilion multi-slice computed tomography (CT) system, which it termed the industry's most powerful such system. TAMS said the Aquilion technology provides an accuracy that makes it possible for cardiologists to more clearly visualize soft plaque and other vessel details inside the coronary artery to better detect heart disease using noninvasive CT technology. It said investigators already are seeing "dramatic opportunities" with the current version, and added that the works-in-progress, next-generation 16-slice system holds the promise of imaging the entire heart in a single rotation.
The company said its automated imaging application, called multiplanar reconstruction, combines with Quantum Detector technology to allow for the accurate imaging of soft tissue. It said the Aquilion 3-D reconstruction enhances surgical planning by allowing clinicians to view a patient's exact anatomy prior to an operation. Accurate and detailed measurements also can be taken in advance to improve the precision of procedures such as stent placements. It added that use of the Aquilion system in conjunction with the Vitrea II workstation from Vital Images (Minneapolis, Minnesota) also performs effective coronary artery calcification scoring studies comparable to those of electron beam CT technology in early detection of heart disease.
(Next month: A full report from ACC.)