Implantable cardioverter defibrillator (ICD) implantation may contribute to a lower incidence of ventricular fibrillation (VF)-related out-of-hospital cardiac arrest treated by emergency medical services (EMS), according to a study published in the September issue of Heart Rhythm, a journal of the Heart Rhythm Society (formerly NASPE; Natick, Massachusetts). Sudden cardiac death (SCD), caused by VF, poses the greatest threat and accounts for half of all cardiac deaths. It is not the same as a heart attack, or myocardial infarction. In VF, the most common abnormal heart rhythm in out-of-hospital cardiac arrest, the heartbeat is rapid and chaotic, which causes the lower heart chambers, or ventricles, to go into a spasm.

"Although there are a number of factors that contribute to these findings, this study has significant clinical importance to prevention strategies and treatment of coronary heart disease, ventricular tachyarrhythmias, and sudden death," said Stephen Hammill, MD, president of the Heart Rhythm Society and a professor of medicine at the Mayo Medical School as well as the director of heart rhythm services for the Mayo Clinic (both Rochester, Minnesota). "It is important that we do everything we can to ensure that the cardiac mortality rate continues to decline," he told Cardiovascular Device Update.

Researchers from the Mayo Clinic examined the incidence rates and trends, since 1985, of patients in the city of Rochester who experienced out-of-hospital cardiac arrest and who received defibrillation of VF by emergency medical personnel and an ICD implant. Twenty-two patients had potentially lethal ventricular arrhythmias averted by their ICD. Termination of potentially life-threatening arrhythmias increased from 1.1 to 3.5 per 100,000 over the study period, and VF out-of-hospital cardiac arrest declined from 26.3 to 7.7 per 100,000.

The study concluded that the incidence of VF out-of-hospital cardiac arrest is declining and the rate of ICD implantation and ICD termination of VF is markedly increasing. Although researchers said that the underlying causes behind the decline "are likely multifactorial," they believe that use of ICD technology was one of the most important therapies that contributed to the decline.

"Identifying high-risk individuals is especially important because approximately one-half of sudden cardiac deaths were not preceded by a diagnosis of coronary heart disease," Roger White, MD, the study's lead investigator, said in a statement. "Considering recent trial results such as MADIT II, we expect that the number of patients who receive a device for primary prevention will increase progressively over the next decade. This trial tells us that we can then also expect the decline in deaths from cardiac arrest to continue."

Hammill agreed with White's assessment, adding that the report "tends to corroborate the studies that have come out recently looking at the value of the defibrillator as primary prevention for sudden death like in MADIT II and SCD-HeFT." Those studies, he noted, appear to show that the use of defibrillators help to reduce the risk of SCD, "and then this study is more of a population study saying 'well, we are seeing that – we're seeing that the incidence of sudden death is dropping as the defibrillator use is increasing.'"

The study noted that the trend toward a decline in emergency medical service-treated VF in Rochester parallels reports from Seattle, Helsinki and Sweden, but he said that this was the first report to investigate the potential causes of this declining trend. "The population-based data reported here expand these prior reports by first demonstrating an overall decline in EMS-treated VF out-of-hospital cardiac arrest and then showing an opposing trend of ICD placement with both primary and secondary termination of ventricular arrhythmias that, in part, may account for the declining VF out-of-hospital cardiac arrests," the report says.

"The sudden death survival [rate] is improving," said Hammill, noting that in Rochester, where there is a good first-responder program, the survival rate for a VF incident is about 40% vs. a rate of less than 5% in larger cities such as Chicago and New York. However, he said "the problem is trying to apply what happens in the 'tight community' of Rochester to New York City."

Panel discusses trial design for CPR devices

In what seemed like another part of the agency's ongoing effort to make the government's regulatory process more transparent for both industry and consumers, the FDA's Circulatory System Devices Panel held an investigational panel meeting in the latter part of September to discuss clinical trial design for cardiopulmonary resuscitation (CPR) devices. Clinical trials for devices in this category can be difficult to perform and evaluate, according to panel members, due to constraints on the usual trial controls, such as informed consent issues, trial blinding concerns and proper study participant inclusion/exclusion criteria.

For example, there are issues surrounding informed consent of patients because sudden cardiac arrest (SCA) is – as its name illustrates – unexpected. And recruiting and enrolling as device sponsors would with a conventional device trail is not always possible. Research into this area is "urgently needed," according to Elisa Harvey, DVM, PhD, an expert in the protection of patient rights and a member of the FDA's Office of Device Evaluation. Beginning in 1996, new FDA regulations addressed the exception of informed consent in similar situations, but more information is needed, she said.

Most recently, the Public Access Defibrillation (PAD) trial relied on this kind of data. PAD was conducted by the National Heart, Lung and Blood Institute (Bethesda, Maryland) and the American Heart Association (Dallas). The results were published recently in The New England Journal of Medicine. The study found that deploying AEDs in public places and training citizens to use them can double the chances of surviving SCA for the general population. The PAD study ran from July 2000 through September 2003 and compared the number of patients who survived to hospital discharge after out-of-hospital cardiac arrest at a community facility where trained volunteers were able to recognize the event, telephone 911, and perform CPR to the number of patients who survived to hospital discharge after out-of-hospital cardiac arrest at a community facility where volunteers could also provide defibrillation with an on-site AED.

"This kind of study is helpful in developing more informed consensus regarding optimal approaches for these types of studies," Harvey said. She noted that the current FDA draft guidance is being revised to incorporate public comments and provide further clarification and that ongoing experience in this area will help. "Sponsors, investigators, IRBs [institutional review boards] and FDA reviewers are still in learning mode with regard to best practices," she said.

"I think this is a very dynamic area of science," said Lance Becker, MD, associate professor of medicine and director of the emergency resuscitation center at the University of Chicago. "What we have today will not be what we have in a year or five years after that. So I commend the agency for its efforts in trying to apply a more exact science to the study process in this area." Becker's research interests include development of new cytoprotective strategies for use in resuscitation, laboratory methods for resuscitation research, and survival from sudden cardiac arrest.

Some of the other areas the panel discussed were inclusion/exclusion criteria, study endpoints, and study design. While its members did not make a list of or take a vote on formal recommendations, the goal of the day's deliberations was to make the panel more proactive in its counsel to industry, according to William Maisel, MD, of Brigham & Women's Hospital (Boston), who chairs the panel.

No Comments