A newly revised set of guidelines, released last month by three prestigious medical groups in the heart therapy sector, promises a healthier outlook both for heart patients and those companies that make pacemakers and the newest generations of implantable cardioverter defibrillators (ICDs). Issued jointly by the American College of Cardiology (ACC; Bethesda, Maryland), the American Heart Association (AHA; Dallas, Texas) and the North American Society of Pacing and Electrophysiology (NASPE; Natick, Massachusetts), the 48-page document updates previous guidelines for implantation of these devices in a way that will have "a major impact on the treatment of arrhythmias," according to Gabriel Gregoratos, MD, chair of the group that wrote the new guidelines and director of cardiology consultant services at the University of California, San Francisco.
The guidelines especially recommend the devices for those who have recovered from a heart attack and their hearts have impaired pumping ability. And some estimates suggest the new therapeutic parameters could help drive access to advanced pacing technology for an estimated 200,000 to 300,000 more people. Mark Schoenfeld, MD, president of NASPE and associate professor of medicine at Yale University School of Medicine (New Haven, Connecticut), told Cardiovascular Device Update that the updated recommendations constitute "the single most important document that exists today that governs the practice of cardiac electrophysiologists."
The original guidance for these treatments, issued in 1998, was characterized by Schoenfeld as "groundbreaking, because it identified the indications for both pacemakers and defibrillators and what indications were appropriate for implantation." But, he added, "So much has happened since that time period. There have been remarkable discoveries over the intervening four years."
Schoenfeld said the guidelines revisions were shaped over a period of at least two years as new data came out from clinical trials, and he pointed, in particular, to data from MADIT II (for Multi-center Automatic Defibrillator Implantation Trial), released this past March showing that in heart attack patients with an ejection fraction of 30% or less, an ICD can still reduce the risk of death by nearly one-third, even if the heart's rhythm appears to be normal day-to-day. Until now, however, ICDs had been recommended only for those patients who had presented with at least a mild arrhythmia or when special testing could provoke such an arrhythmia. The MADIT II study, using ICDs made by Guidant (Indianapolis, Indiana) garnered headlines for being halted last year, before its completion, because of its broad success. The FDA in July approved expanded uses for Guidant's ICDs. And Schoenfeld said that this research helps to translate the general knowledge concerning pacing benefits into everyday practice, which has been hindered by reimbursement issues.
"Even though the medical literature would dictate and warrant defibrillator implant, [caregivers'] hands have been constrained," he said, those constraints the result of delays in both FDA approvals and reimbursement by Medicare. "Physicians have been caught in the difficult situation of knowing what may best serve a patient but not have the guidelines clearly delineated," he said. "I do believe CMS [Centers for Medicare & Medicaid Services] and the third-party payers will follow these guidelines. What else can they follow? These guidelines address the medical and scientific facts." Schoenfeld said that CMS would not be able to resist reimbursement of these technologies on the basis of dollars, since these technologies offer clear cost-effectiveness.
One of the major recommendations of the guidelines is the approval of biventricular pacing for patients whose hearts not only pump with too little force, or ejection fraction, but that also fail to beat in synchrony from the left to right side. Thus the guidelines support the use of new biventricular pacing devices that are coming on the market. Overall, Schoenfeld said, "these new recommendations point out the need for patients to know as much about their heart as possible, including whether they have a decreased ejection fraction, and for physicians to place more emphasis on ejection fraction as a way of assessing the risk of patients under their care. Ejection fraction may turn out to be as important in determining patient outcome as cholesterol is."
Defibrillation, if delayed, may be harmful
About 10 minutes after the onset of cardiac arrest, little or no energy remains in the heart and it loses its ability to pump blood. And it is well-known that defibrillation of a heart attack patient has to come within 10 minutes – and the earlier the better – to do any good. But now, a new study warns against defibrillation after 10 minutes, indicating that it won't help and may do additional harm. Performed by researchers in the department of emergency medicine at the University of Pittsburgh School of Medicine (Pittsburgh, Pennsylvania), the study indicates that other therapies should be attempted before defibrillation after the 10-minute window closes. Results were reported at last month's meeting of the American College of Emergency Physicians (ACEP; Irving, Texas) in Seattle, Washington.
In animal studies, the researchers reproduced two scenarios for sudden cardiac arrest in real time, waiting between eight to 10 minutes and 10 to 12 minutes from the onset of cardiac arrest to begin resuscitation, about the same time frame for first responders to arrive at the scene. After the desired level of cardiac arrest was reached, the subjects were treated with one of three strategies: immediate defibrillation; a combination therapy of cardiopulmonary resuscitation (CPR) first, intravenous drugs second and defibrillation last; or intravenous drugs and CPR administered simultaneously before defibrillation.
Of the three strategies, the researchers found immediate defibrillation was least effective and that there was a significant delay in restored circulation. There were no significant differences in the subjects that were resuscitated at eight to 10 minutes or at 10 to 12 minutes.
James Menegazzi, PhD, lead author of the study, said, "Although rapid defibrillation is hands down the best method to resuscitate victims minutes after sudden cardiac arrest, we now have additional evidence that indicates the longer someone is in prolonged cardiac arrest, providing immediate defibrillation is not the most effective way to resuscitate because the injured heart is only further damaged by shocking it. This evidence suggests we should try other treatment options before defibrillation." Menegazzi is a research professor of emergency medicine at the University of Pittsburgh School of Medicine. The study was funded in part by the Pittsburgh Emergency Medicine Foundation.
Another study reported at the ACEP meeting focused on the after-effects of cardiac arrest, specifically the adverse effects of clotting that begin as quickly as six minutes after arrest and may hamper resuscitation. Even after resuscitation, blood clots may form within blood vessels and lead to organ failure and death. The research was conducted in the department of emergency medicine at the University of Pittsburgh School of Medicine. The research attempted to determine the extent to which increased blood clotting occurs in patients who suffer cardiac arrest outside the hospital. Using blood samples collected from 28 patients, the researchers found that all but one patient showed evidence of clot formation within the veins, and that clotting increased the longer the patient was in cardiac arrest.
"These findings will add to our understanding of the changes that occur during cardiac arrest outside the hospital so that we can design strategies to improve survival," said Clifton Callaway, MD, assistant professor of emergency medicine at the university.
Task force sees estrogen/progestin heart risk
The U.S. Preventive Services Task Force last month recommended against the use of combined estrogen and progestin therapy for preventing cardiovascular disease and other chronic conditions in postmenopausal women. The task force, sponsored by the Agency for Healthcare Research and Quality (AHRQ; Washington), said it found evidence for both benefit and harm of the combination therapy, a commonly prescribed hormone regimen. However, the task force concluded that harmful effects of the combined therapy are likely to exceed the chronic disease prevention benefits for most women.
The task force further concluded that the evidence is insufficient to recommend for or against the use of estrogen alone for prevention of chronic conditions in postmenopausal women who have had a hysterectomy. A study of estrogen therapy in women who have had hysterectomies is continuing as part of the National Institutes of Health's (Bethesda, Maryland) Women's Health Initiative because it has not yet found clear benefit or harm. Estrogen alone, or estrogen and progestin together, are commonly referred to as hormone therapy or hormone replacement therapy.
The scientific review for the task force examined hundreds of studies, including a recently terminated trial within the Women's Health Initiative, which reported the effects of taking combined estrogen and progestin therapy on a variety of chronic diseases. The task force concluded that combined hormone therapy could increase bone mineral density and reduce the risk of fractures and may reduce the risk of colorectal cancer. They found equally strong evidence, however, that combined hormone therapy increases the risk for breast cancer, blood clots, stroke, and gallbladder disease. In addition, evidence reviewed by the task force suggests that hormone therapy does not reduce the risk of heart disease and that estrogen and progestin combined actually increase the risk of heart attacks.
An estimated 14 million American women take hormone therapy to help relieve hot flashes and other menopausal symptoms as well as to prevent chronic conditions such as heart disease, which is the leading cause of death among U.S. women. The use of hormone therapy to treat hot flashes or other symptoms of menopause was not evaluated by the task force. The task force concluded that women considering starting or continuing hormone therapy to relieve menopausal symptoms should discuss their individual risks for specific chronic conditions and personal preferences with their clinician.
"These recommendations reflect the scientific evidence concerning the long-term effects of HRT, but there are no easy answers for women," said task force chairman Alfred Berg, MD, professor and chair, Department of Family Medicine, University of Washington (Seattle, Washington).
Gene therapy for heart failure in hamsters
An article in the August issue of Nature Medicine indicates a positive potential for gene therapy of the heart in hamsters. Currently, the only curative procedure for end-stage heart failure – a leading cause of death in Western countries – is an organ transplant. But even this last-resort surgery is curtailed by the chronic lack of donor hearts. Experimental gene therapy for heart failure and chronic heart-muscle diseases has been tried by many cardiac researchers for many years, but so far without signal therapeutic success. It has been limited by the short-term effects, myocarditis, and low efficiency of gene transfer delivered by traditional viral vectors.
Authors of the Nature Medicine article are at the University of California San Diego's Institute of Molecular Medicine. They used the rAAV delivery vehicle to express human phospholamban (PLN) – a key heart-muscle regulator – in a cohort of 59 cardiomyopathic hamsters. At five to six weeks of age, those rodents initially showed cardiac contractile dysfunction, followed by progressive cardiac dilation and heart failure. The gene transfer treatment protected contingents of the animals' heart muscle cells from plasma-membrane disruption for 28 to 30 weeks.
The journal article said the study "describes a new in vivo protocol for the transcoronary [injecting the gene directly into the arteries] delivery of genes that holds considerable promise for the long-term molecular remodeling of the failing myocardium." It added, "Using this system, we have achieved high efficiency (over 60% of the ventricular muscle) and long-term expression (over seven months)."
The paper noted, "Given that there is currently no therapy for end-stage heart failure aside from heart transplantation, future studies are warranted to translate these findings into larger animal models and the clinical setting."
Studies pinpoint statin non-compliance
The failure of many people to take prescribed drugs is a well-known attribute of patient behavior, but two new studies show the problem may be epidemic among senior who have been prescribed cholesterol-lowering statins.
A recent study by researchers at Brigham and Women's Hospital (Boston, Massachusetts) following the prescription-filling patterns of 34,500 men and women, age 65 and older. The study observed a large drop in statin prescriptions filled after six months. After that, the decline continued even more steeply, and after five years only 25% of the seniors were taking the medications. The second study was conducted at Toronto General Hospital (Toronto, Ontario), following more than 140,000 people over the age of 65 who had been prescribed. As might be expected, those seniors who had suffered heart attacks were most likely to continue taking the drugs, with 40% of them continuing on the drugs after two years. But at the same point, only 25% of those who had experienced no heart attack continued taking the drugs.
In both cases, the researchers concluded that the cost of medications was not a key issue. Rather, they theorized that many of the seniors stop taking the drugs simply because they considered themselves symptom-free and were unaware of the risks of high blood cholesterol.