New research presented at the American Heart Association (AHA; Dallas) meeting in New Orleans suggests that following an unwitnessed cardiac arrest – that is, the patient has a heart attack but by the time help arrives at least 10 minutes have passed – it may still be possible to avoid brain damage.
The new study, "Neurological Recovery 'Life after Death' following Total Brain Ischemia with Controlled Reperfusion," was presented by Bradley Allen, MD, and his UCLA School of Medicine colleagues at the Resuscitation Satellite Symposium of the AHA meeting over the weekend. The research included a blood conditioning process using a leukocyte (white blood cell) reduction filter, the LeukoGuard BC Filter from Pall Life Sciences, a business of Pall Corporation (East Hills, New York).
"What we've done is we've salvaged the brain after 30 minutes of no blood flow," Allen told Medical Device Daily. "Most people think the brain starts to die within four to five minutes [without oxygen] so to be able to salvage the brain after 30 minutes was thought to be impossible."
Allen says the research may offer hope for patients undergoing sudden death and stroke.
"The stroke thing came up because stroke is the same type of problem in the sense that a stroke causes no blood flow to a part of the brain, where as sudden death is no blood flow to the entire brain," he explained.
The study, using a porcine model, showed that the brain suffers either death or massive injury when normal blood flow is resumed following 30 minutes of ischemia (cessation of blood flow), as occurs during cardiac arrest.
In contrast, according to the study, if the pig brain, after 30 minutes of ischemia, received just 20 minutes of controlled delivery of "conditioned blood" — a process called controlled reperfusion – it recovered quickly, dramatically and often completely. In the study, the blood conditioning process included passing blood through the Pall LeukoGuard BC Filter before it was delivered to the brain.
Allen told MDD that in order for the research to have an impact in real-world situations, "It would mean that we would have to change our approach for treating both of these diseases." For example, he said, the current thinking is that intervention such as cardiopulmonary resuscitation (CPR) needs to be performed immediately to prevent massive brain damage or death. That's true, he said, when the event is witnessed and CPR is started immediately. However, the study implies that there needs to be a major change in conventional thinking in the treatment of unwitnessed cardiac arrest.
The implications of the findings by Allen and his colleagues are that many more patients might survive if sufficient time for the correct intervention and controlled reperfusion are available. Additionally, of those who initially survive stroke, it is commonly reported that roughly half suffer permanent brain damage. The controlled reperfusion protocol could substantially reduce this adverse outcome, according to Pall.
According to the company, Allen and his longtime colleague, Gerry Buckberg, MD, have together studied controlled reperfusion for the last 25 years, and have shown that this procedure effectively can avoid injury to the heart, lungs and lower extremity. The investigators studied the contribution of white blood cells in their system. They believe leukocyte reduction by filtration is an important component for a successful outcome, Pall noted.
"We have found that leukocyte reduction is a very important part of preventing neurological damage ... we do not believe there is a magic bullet, but the biggest bang for the buck did involve removing leukocytes," Allen said.
Allen's presentation sparked a "huge response" among AHA attendees. He said about 20 people stood up to ask questions immediately following his presentation, and when time ran out several others approached him after the session. "So I was asking questions for about an hour," he told MDD.
In other AHA news:
• Drug-eluting stents reduced the risk of revascularization, heart attack and death in diabetics as compared with bare-metal stents in the largest observational comparison, researchers reported. The results from The Drug-eluting and Bare Metal Stenting in Patients with Diabetes Mellitus: Results from the Mass-DAC Registry, were presented as a late-breaking clinical trial. The study is simultaneously published in Circulation, the journal of the AHA.
"We actually saw a significant benefit from using drug-eluting stents in this patient population," said Laura Mauri, MD, principal investigator of the study and assistant professor of medicine at Brigham and Women's Hospital and Harvard Medical School (both Boston). "First, they significantly reduced the need for repeat procedures which included repeat stenting or bypass surgery. Second, they were associated with lower rates of death and heart attack. So, as a result we can say that these stents appear to be safe in diabetic patients, whose diabetes puts them at higher risk of mortality and heart attack than the general population."
According to the researchers, people with diabetes make up about a third of all patients undergoing percutaneous coronary interventions (PCI) to reopen blocked blood vessels. In PCI with stenting, a balloon-tipped catheter is threaded into the artery to the point of blockage. Then, the balloon is inflated to open the vessel and a mesh metal stent — either bare-metal (BMS) or drug-eluting (DES) — is inserted to keep the channel open. DES are coated with a drug that fights the proliferation of cells that can block the artery.
In the largest population-based comparison of stents in diabetics, researchers used data from a mandatory state registry. They identified 5,051 diabetics who underwent PCI at acute-care, non-federal hospitals between April 2003 and September 2004. Diabetic patients at those hospitals were about twice as likely to get DES compared to BMS (66.1% vs. 33.9%), researchers said.
At three years of follow-up, the unadjusted cumulative endpoint of death was 14.4% for DES patients compared to 22.2% for BMS patients, Mauri said.
The researchers then matched a subset of 1,476 DES and 1,476 BMS patients to control for 63 potential confounders such as concurrent conditions and medications. In that comparison, they found the risk-adjusted mortality at three years was 17.5% for DES patients vs. 20.7%, a small but significant 3.2% absolute reduction in mortality in DES patients, with no excess adverse events. The choice of BMS or DES was not randomized, but was done at the direction of the treating physician, so it is possible that the patients given DES were different in the number of blood vessel or other characteristics, the researchers noted.
Although three-year data were not yet available for rates of heart attack and target vessel revascularization, at two years of follow-up those rates were lower in the DES group compared to the BMS group.
• Catheter ablation has been shown in a randomized clinical trial to significantly outperform anti-arrhythmic drug (AAD) therapy for the treatment of symptomatic paroxysmal atrial fibrillation, or AFib.
In data presented at the AHA meeting, patients receiving cardiac ablation with the NaviStar ThermoCool catheter from Biosense Webster (Diamond Bar, California) were significantly more likely to be free of recurring AFib at nine months after initiation of treatment and experienced fewer serious adverse events after 90 days than those receiving AAD therapy.
"This is the first time in an FDA-monitored, controlled clinical study that catheter ablation has been shown to outperform traditional medical therapy," said David Wilber, MD, primary investigator (PI) of the study and the George M. Eisenberg Professor of Cardiovascular Sciences and director of the Division of Cardiology at Loyola University Medical Center (Maywood, Illinois). "These data are extremely important to the electrophysiology community widely adopting alternative treatments to traditional medical therapy, which can often cause significant side effects for patients suffering from this debilitating condition."
Currently, there are no ablation catheters approved for marketing by FDA for the treatment of AFib. Biosense said it submitted a pre-market approval (PMA) supplement for an AFib indication for its ThermoCool catheter, based on this study data. The PMA supplement was granted priority review by FDA, which will convene the Circulatory System Devices Advisory Panel on Nov. 20 in Gaithersburg, Maryland to review the application.
The clinical trial was a randomized, unblinded and controlled evaluation of symptomatic, paroxysmal AFib patients who were refractory to at least one AAD and had at least three episodes of AFib in the six months prior to randomization. A total of 167 patients were enrolled from 19 sites throughout the world and the primary effectiveness endpoint was freedom from documented symptomatic AFib recurrence following procedural endpoint confirmation and absent new AAD use or repeat ablation outside of protocol-defined criteria.
The probability of chronic success was 62.7% for patients receiving NaviStar ThermoCool catheter ablation at the nine-month effectiveness evaluation period, which is significantly superior to the 17.2% probability for the group of patients treated with AAD, the company said. The ThermoCool catheter ablation group also demonstrated a substantial reduction in symptomatic AFib recurrence compared with patients treated with AAD.
Additionally, the catheter ablation group demonstrated an excellent safety profile with no device-related serious adverse events within seven days post ablation. There was no clinically significant pulmonary vein stenosis in patients receiving ablation, and the incidence of serious adverse events in the catheter group in the 90 days following initiation of therapy was observed to be about half that in the AAD group.
The NaviStar ThermoCool catheter is FDA approved for the treatment of Type 1 atrial flutter, and recurrent drug/device refractory sustained monomorphic ventricular tachycardia due to prior myocardial infarction (heart attack), two types of cardiac arrhythmia.