Clinical and Industry News

Severity of STEMI Dependent on Time of Day

The size of a heart attack and subsequent left ventricular function are significantly different based on the time of day of  onset of ischemia, according to a first of its kind study in humans, published online in Circulation Research. The greatest amount of injury to the heart occurs when individuals have a heart attack between 1:00 am and 5:00 am.

In previous research, the infarct size in rodents following ischemia and reperfusion exhibited a circadian dependence on the time of coronary occlusion. A circadian rhythm is an endogenously driven, roughly 24-hour cycle in biochemical, physiological or behavioral processes. Previously, it was unknown if a similar circadian dependence of infarct size occurs in humans.

“We were trying to ascertain whether the time of day of when a heart attack occurs influences the amount of damage that the heart sustains, or was this just a phenomenon exhibited in rodents,” said the study’s senior author Jay H. Traverse, MD, a cardiologist at the Minneapolis Heart Institute at Abbott Northwestern Hospital in Minneapolis and physician researcher with Minneapolis Heart Institute Foundation.

A retrospective analysis of 1,031 patients in the Level 1 acute MI database with a ST-elevation myocardial infarction (STEMI), referred for primary percutaneous coronary intervention (PCI) with known ischemic times between one and six hours, identified 165 patients with their first heart attack who had occluded arteries on presentation without evidence of pre-infarction angina or collateral blood flow.

All 165 patients had well-defined ischemic times and the data were supported by a subgroup with cardiac MRI measurements of infarct size, or size of heart attack, and area-at-risk.

The researchers observed that the extent of infarct size was significantly associated with time of day onset of infarction. The greatest myocardial injury occurred at a 1:00am onset of ischemia and 5:00am onset of reperfusion with the peak injury being 82 percent higher than that recorded at lowest time of injury.

What are the implications of these findings? “It is important to understand that the heart’s ability to protect itself against more severe damage varies over a 24-hour cycle. Identifying those protective changes may be particularly relevant for pharmaceutical manufacturers that are seeking to develop cardioprotective drugs,” Traverse explained.

Low Risk? Women, Young Men Responsible for Large Portion of STEMIs

In a contemporary cohort of acute heart attack patients, 70% of the patients were unaware they had coronary heart disease (CHD) prior to the event and 60% of those patients were women or young men. However, these two subgroups are less likely to qualify for aggressive preventive therapy and, therefore, do not receive preventive medications that could reduce the heart attack risk, according to a study presented at the American Heart Association (AHA) scientific sessions in Orlando, Fla.

“For those patients with known coronary disease, the evidence and guidelines are fairly clear about the benefit of aggressive medical therapy, including an aspirin and statin, regardless of your age or gender,” says Michael Miedema, MD, a cardiology fellow at the University of Minnesota working in collaboration with researchers at the Minneapolis Heart Institute at Abbott Northwestern Hospital in Minneapolis. “However, for patients without known coronary disease, the optimal approach is much less clear. We currently only treat high-risk patients but our data show that women and young males, who rarely qualify as high risk, make up a substantial portion of the current heart attack population.”

The researchers assessed the Minneapolis Heart Institute’s Level One heart attack program to better understand the presence of premature CHD in patients without a prior history of CHD presenting to their facility with ST-elevation myocardial infarction (STEMI).

From March 2003 to January 2010, 3,038 patients were evaluated, and 70.3% did not have previously diagnosed CHD prior to their heart attack and 41.7% qualified as premature. Despite similar rates of high cholesterol, patients with premature disease (men 55 years or younger, women 65 years or younger) were approximately half as likely to be on a statin prior to their heart attack (10.45 vs. 19.4%). Aspirin and combination therapy were being used significantly less often as well.

The Framingham Risk Score is the most commonly used risk calculator, using the patient’s age, gender and risk factors such as cholesterol and blood pressure to determine the potential risk for a cardiac event. However, Miedema suggests that the Framingham Risk Score is heavily weighted toward age and gender.

“If you’re an older male, you’re much more likely to qualify for preventive therapy while females and younger males often do not meet criteria despite similar risk factors,” Miedema says. “While older males are still the most likely group to have heart attacks, we have shown that women and patients with premature disease make up a substantial portion of the heart attacks we are seeing and very few of these patients are on the medications which research has shown to prevent heart attacks. Better methods of risk assessment could potentially allow us to target more people truly at high risk for an event and avoid excessive treatment of those who are low risk.”

Based on the study findings, the study authors concluded without improved preventive care strategies, the possibility of further decreasing the rate of STEMIs in the United States may be “challenging.”

Scarring Necessary Evil to Prevent Further Damage After MI

After a heart attack, the portions of the heart damaged by a lack of oxygen become scar tissue. Researchers have long sought ways to avoid this scarring, which can harden the walls of the heart, lessen its ability to pump blood throughout the body and eventually lead to heart failure. But new research from the University of North Carolina at Chapel Hill School of Medicine shows that interrupting this process can weaken heart function even further.

In a study appearing online November 15, 2011, in the EMBO Journal, the investigators observed that cells in the outer layer of the heart generated scar tissue. But when they blocked these cells from doing so, they essentially demonstrated that when fixing a broken heart, timing may be everything.

“We now know that scarring is a good thing, because it prevents a precipitous decline in heart function immediately after heart injury,” said Arjun Deb, MD, senior study author and assistant professor of medicine and cell and molecular physiology at the UNC School of Medicine. “The question is not whether, but when it makes the most sense to manipulate the cells of the heart to decrease scarring and enhance regeneration.” Deb is also a member of UNC’s McAllister Heart Institute and the Lineberger Comprehensive Cancer Center.

Regeneration happens naturally in lower organisms like zebrafish, the striped, thumb-sized inhabitants of household aquariums, but for some reason, not in higher organisms like humans. Years ago, researchers noticed that the epicardium was playing an important role in regenerating the zebrafish heart after injury. But what role the epicardium might have in an injured mammalian heart was an open question.

By studying a mouse model of cardiac injury, Deb and his colleagues found that the epicardium of the mammalian heart was also activated after a heart attack. But unlike in zebrafish where the epicardium contributed to generation of heart muscle cells, in the mouse the epicardium generated fibroblasts, the fibrous cells that underlie scar tissue.

The researchers then found that a protein called Wnt1, which they had formerly shown to enhance function of human vascular stem cells, was driving stem cells within the epicardium to become fibroblasts. They wondered if interrupting this molecular pathway could ameliorate scarring and improve heart function. Surprisingly, when they interrupted Wnt1 signaling in genetically engineered mice, the mutants developed heart failure within 2 weeks after cardiac injury.

“There are clearly evolutionary parallels between the zebrafish and the mouse, but there must be some sort of a selection pressure in mammals to respond to heart injury by scarring, because if we interrupt this process then the heart quickly fails following injury,” said Deb. “In organisms where there is a high pressure of blood flow, these cells may need to turn into scar tissue to maintain the tensile strength of the heart wall and prevent catastrophic rupture,” speculates Deb.

Now Deb and his colleagues are genetically manipulating the stem cells residing in the epicardium at later time points to see if they can coax them to stop turning into fibroblasts and start forming heart-regenerating myocytes. If so, the approach could prove to be an invaluable way to help patients recover from a heart attack.

Mitral Valve Replacement: Asymmetric Design Better

The heart’s valves, which guarantee the unidirectional flow of blood from one chamber to another, are asymmetrical. For example, the two flaps of the mitral valve vary in size by up to 70%.

This arrangement, says fluid mechanicist Marija Vukicevic from the University of Trieste (now a researcher at Clemson University), naturally drives blood flow along the lateral wall of the ventricle. From there, blood takes a smooth turn, creating a large vortex that redirects the blood toward the aorta, through which it exits out into the body.

Mechanical heart valves, however, are symmetric in design, with both flaps of a mitral valve replacement of identical size, and that, Vukicevic and colleagues have found, disrupts the flow of blood.

“Blood flow in the left ventricle is characterized by a physiological vortex that disappears when a symmetric mechanical prosthesis is implanted,” she says. With such prostheses, which are implanted into an estimated 60,000 patients each year in the United States, blood flows across the ventricular chamber then hits the opposite side instead of taking a turn, leading to a higher effort in the heart muscle and a disruption in its regulatory mechanism.

To see if a more naturally asymmetric design could improve blood flow, Vukicevic, along with Gianni Pedrizzetti of the University of Trieste and colleagues created aluminum models of asymmetric valves, similar in size to the valves of an adult human heart. The valves were tested in a mock ventricle, made of silicon, through which the researchers could visualize fluid flow. The pattern and rate of flow through the valves, the researchers found, closely matched that of a healthy heart. “We recommend that industries test asymmetric prototypes for mitral valve replacement,” she says.

Pre-Hospital Administration of Thrombolytic Therapy May Help Most Critical Patients

Cardiologists are quick to point to statistics showing that the door-to-balloon treatment time for heart attack patients has dropped significantly in the past few years. But a retrospective study reveals that those who call 9-1-1 are most likely to have suffered a severe heart attack and despite receiving treatment quickly, they are still dying at unacceptable rates, say researchers at The University of Texas Health Science Center at Houston (UTHealth).

Results from the large retrospective study were presented at the American Heart Association’s Scientific Sessions 2011 by lead author James J. McCarthy, MD, assistant professor of emergency medicine at the UTHealth Medical School and director of the Emergency Center at Memorial Hermann-Texas Medical Center.

The results of the study revealed that patients who call 9-1-1 instead of transporting themselves to the emergency room arrive 30 minutes faster and have shorter door-to-balloon times (56 minutes versus 70). Unfortunately, in spite of this, they are more likely to be in shock (10.7% versus 3.5), suffer heart failure (9.9% versus 6.3) by the time they get to the hospital and more likely to die during their hospitalization (7.2% versus 2.4).

“Those who call an ambulance are three times more likely to die because their disease is worse. They are much sicker,” McCarthy said. “We suspect that it means they have a larger infarct. It’s a vulnerable population that despite rapid emergency medical services (EMS) and hospital care still has higher mortality.”

Previous UTHealth research has shown that if the artery is unblocked in the first hour after a heart attack, there is minimal damage. After three hours, most of the damage has been done, so UTHealth researchers have been concentrating on how to shorten that time to two hours or less.

The only way to lower the current time from symptoms to opening the artery is to treat the patient in the ambulance, McCarthy said. A year ago he presented results of a UTHealth clinical trial called Pre-Hospital Administration of Thrombolytic Therapy with Urgent Culprit Artery Revascularization (PATCAR). That trial showed that the mortality rate of patients arriving via EMS could be lowered to 2.9% by giving them a low dose of a clot-busting drug intravenously before they arrived at the hospital. The research was a collaboration of UTHealth, Memorial Hermann Heart & Vascular Institute-Texas Medical Center (HVI) and the Houston Fire Department.

“We know we’ve optimized the hospital system and integrated that with EMS, but for the cohort that calls 9-1-1, that’s still not enough,” he said. “We need to figure out something else.” The researchers are seeking additional funding to expand PATCAR to more patients.

The researchers looked at 37,715 patients in the American College of Cardiology’s National Cardiovascular Data Registry. The presentation title is “EMS Transport of STEMI Patients Shortens Ischemic Times and is Associated with a Higher Risk Population: Results from the ACTION Registry.”

CT Angiography for CAD Linked to Higher Rates of Cardiac Procedures and Greater Costs

Use of computed tomography (CT) for the diagnosis of coronary artery disease is associated with a higher rate of subsequent invasive cardiac procedures and higher health-care spending. That’s according to an observational study of Medicare recipients conducted by researchers at the Stanford University School of Medicine.

In the study, published in the Nov. 16 issue of the Journal of the American Medical Association, patients who underwent coronary CT angiography were about twice as likely to have a subsequent invasive cardiac procedure as patients who underwent a stress test, a more common diagnostic procedure. CT angiography was also associated with higher total health-care spending.

Senior author Mark Hlatky, MD, professor of medicine and of health research and policy, said the findings raise questions of whether patients are benefiting from the additional procedures. “We don’t know if those extra procedures will ultimately save lives and lead to better quality of life,” he said, noting that they definitely increased costs. “Our study suggests that we need more definitive clinical trials to show whether patients are better off as a result of having CT angiography instead of a stress test.”

“CT angiography is a potential game-changer with respect to how we evaluate patients with suspected heart disease,” said Hlatky, adding that the number of coronary CT angiography procedures conducted on Medicare beneficiaries has increased steadily since the procedure first became eligible for reimbursement in 2006.

Experts predict a substantive growth in the use of coronary CT angiography over the next decade, but the impact of the test in practice hasn’t been known. “Most prior studies have simply evaluated the accuracy of coronary CT angiography compared with the results of a standard invasive coronary angiogram, and haven’t looked at how the information was used,” said Hlatky. “Before we did this study, it wasn’t clear whether a CT angiogram would lead to more testing and more unnecessary procedures, or whether it would reduce the need for further testing and save money. We needed real data to document how coronary CT angiography would be used in practice.”

For this study, Hlatky and his colleagues examined the health-care use and spending among patients evaluated for suspected heart disease. This issue hadn’t been addressed in previous studies.

The researchers studied 282,830 Medicare patients who received noninvasive testing for coronary artery disease between 2005 and 2008. The median age of the study cohort was 73.6 years; 46% were male, and 89% were white. In the group, myocardial perfusion scintigraphy, a noninvasive imaging test that has been considered the most powerful technique for predicting future coronary events, was the most frequently used diagnostic test, followed in order by stress echocardiography, exercise ECG and coronary CT angiography.

The researchers examined outcomes in the six months after the patients were tested, looking at cardiac catheterization, coronary revascularization, heart attack, all-cause mortality and total and cardiac-related Medicare spending. After running their analysis, they found that those patients who received coronary CT angiography were about twice as likely to have a subsequent invasive cardiac procedure as patients who underwent a stress test. They also found that patients who received the CT angiography were nearly twice as likely to have a subsequent cardiac catheterization as patients who had the myocardial perfusion scintigraphy, and roughly 2.5 times as likely to undergo coronary revascularization.

These findings weren’t a real surprise to Hlatky, who pointed out that it’s highly unlikely for any older person to have completely normal-looking vessels. “If you pull a 75-year-old off the street and give him this test, it’s unlikely that the coronary arteries will be completely normal,” he said. The high-tech, sensitive nature of the test means that problems were being detected that led to further testing and more invasive treatments like coronary revascularization.

While finding abnormal arteries might sound like a good thing, the concern is that the test may lead to overdiagnosis and potential overtreatment. Perhaps the patients who received more tests and treatment would have done as well or better if they had been treated with medications rather than revascularization procedures. “We don’t know whether the patients are better off for having this additional testing and higher spending,” said Hlatky.

The researchers also found that heart-related health-care spending was nearly 40% higher among patients who received coronary CT angiography compared with myocardial perfusion scintigraphy, and nearly twice as high compared with patients who underwent stress echocardiography or exercise ECG.

Importantly, although it was associated with a slightly lower likelihood of hospitalization for heart attack, coronary CT angiography was associated with a similar likelihood of all-cause mortality as the other tests at the six-month mark. But, the researchers wrote, “A longer-term perspective is needed to fairly asses the association of mode of noninvasive testing with subsequent mortality.”

Noting that the effect of coronary CT angiography testing on subsequent cardiac events and patients’ quality of life is still unknown, Hlatky said, “The policy implication is that we need clinical outcome studies of coronary CT angiography to see whether the higher rates of invasive procedures and spending are worthwhile.”

The National Institutes of Health recently launched a randomized multicenter trial, known as the Prospective Multicenter Imaging Study for Evaluation of Chest Pain or PROMISE, study, to test how the choice of initial diagnostic test (coronary CT angiography or stress testing) affects patient outcomes. Stanford is one of the trial sites; the work is being led by Michael McConnell, MD, professor of cardiovascular medicine.

Increasing Dosage of Clopidogrel for Patients With Genetic Variation Improves Response to Medication

Yet even with 300 mg daily of clopidogrel, these individuals unlikely to achieve optimal platelet inhibition

Among patients with stable cardiovascular disease who have a genetic variation that diminishes the response to the antiplatelet drug clopidogrel, tripling the standard daily dosage of this medication resulted in improved platelet reactivity, according to a study appearing in JAMA.

“Variants in the CYP2C19 gene influence the pharmacologic and clinical response to the standard 75-mg daily maintenance dose of the antiplatelet drug clopidogrel,” according to background information in the article. Variability in the pharmacodynamic response to clopidogrel is well recognized, and patients with higher platelet reactivity while receiving clopidogrel are at increased risk of adverse cardiovascular events. “ ..data are needed to offer guidance as to what might constitute optimal treatment strategies in patients with loss-of-function CYP2C19 alleles [one of a number of alternative forms of the same gene occupying a given position on a chromosome; an alternative form of a gene].”

Jessica L. Mega, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues conducted a multicenter, randomized trial to test whether maintenance doses of up to 300 mg daily of clopidogrel can improve platelet reactivity in the setting of loss-of-function CYP2C19 genotypes, particularly among heterozygotes (a person possessing two different forms of a particular gene, one inherited from each parent), who constitute approximately 25% to 45% of the population, depending on racial background. The trial (ELEVATE-TIMI 56) enrolled and genotyped 333 patients with cardiovascular disease across 32 sites from October 2010 until September 2011. Patients received maintenance doses of clopidogrel for 4 treatment periods, each lasting approximately 14 days, based on genotype. In total, 247 noncarriers of a CYP2C19*2 loss-of-function allele were randomized to receive 75 and 150 mg daily of clopidogrel (2 periods each), whereas 86 carriers (80 heterozygotes, 6 homozygotes [having two identical gene alleles at the corresponding site on a chromosome]) were randomized to receive 75, 150, 225, and 300 mg daily. Two methods were used to measure platelet function. The average age of the patients was 60 years, 75% were male, 57% had a history of heart attack, and 97% had a history of percutaneous coronary intervention.

Among the main findings of the researchers was that higher maintenance doses of clopidogrel in patients carrying a CYP2C19*2 allele significantly reduced platelet reactivity. Also, daily maintenance doses of 225 mg of clopidogrel or greater in CYP2C19*2 heterozygotes improved platelet reactivity levels that were at least equivalent to what is achieved with 75 mg daily of clopidogrel in noncarrier patients with cardiovascular disease. When evaluating the CYP2C19*2 homozygotes, the researchers saw a trend toward less platelet reactivity with higher maintenance doses of clopidogrel; however, even with 300 mg daily of clopidogrel, these individuals were unlikely to achieve optimal degrees of platelet inhibition.

There were no deaths, cerebrovascular events, or major or minor bleeding events as measured by TIMI (Thrombolysis in Myocardial Infarction) scales.

“These data help define how patients with different CYP2C19 genotypes respond to clopidogrel maintenance dosing strategies and provides useful information to guide further clinical studies,” the authors conclude.

Heart Disease Linked to Evolutionary Changes That May Have Protected Early Mammals from Trauma

Can a bird have a heart attack? A study by researchers at the Perelman School of Medicine at the University of Pennsylvania suggests that cardiovascular disease may be an unfortunate consequence of mammalian evolution. The study, published in Blood, demonstrates that the same features of blood platelets that may have provided an evolutionary advantage to early mammals now predispose humans to cardiovascular disease.

“The biology of platelets has been studied in great detail in the context of human disease, but almost nothing is known about why mammals have platelets, whereas no other species do,” said lead study author Alec A. Schmaier, PhD, an MD/PhD student in the lab of Mark Kahn, MD, professor of medicine at the University of Pennsylvania. “This new line of research suggests that platelets could have allowed mammals to better survive traumatic injury by being able to form cellular clots in arterial blood vessels. The price for this evolutionary change may be modern cardiovascular diseases.”

Despite being a vital element of the blood clotting system, platelets are only found in mammals, whereas all non-mammalian vertebrates, including birds, have thrombocytes. About twice the diameter of platelets, thrombocytes contain a nucleus. Studies performed in the 1970’s suggested they have a clotting function similar to platelets, but extensive studies of thrombocytes using modern experimental techniques have not been performed.

The research team focused their study on birds (compared to fish or reptiles, for example) because birds and mammals both have a high pressure arterial system. Birds in fact have higher cardiac output and blood pressures than mammals do. Therefore, the challenge for hemostasis should be similar between a mammal and a bird. However, in the present study, using molecular and physiologic techniques, the Penn researchers discovered that avian thrombocytes express most of the same proteins as platelets, with two key exceptions: thrombocytes express a significantly lower level of one essential platelet protein (the fibrinogen receptor) and are completely deficient in another (the adenosine diphosphate receptor) that function in a pathway required to form occlusive clots in the arterial system and are the primary targets of anti-platelet medications. In collagen flow-chamber experiments, the research team found that thrombocytes could not form 3-dimensional aggregates under high-flow conditions, a key step in the pathogenesis of stroke and heart attack.

Collaborative studies with colleagues at Penn’s School of Veterinary Medicine, Karen Rosenthal, DVM, MS, and Jeff Runge, DVM, and Tim Stalker, in Department of Medicine-Hematology/Oncology, at the Perelman School of Medicine, next compared the ability of platelets and thrombocytes to form intra-vascular clots in mice and similarly sized parakeets. The mice, but not the birds, developed clots that prevented blood flow after arterial injury due to the ability of platelets, but not thrombocytes, to stick to each other under high flow conditions.

Although the researchers caution that this prediction cannot be tested in all contexts, the finding that equivalent degrees of arterial vessel wall injury in vessels of similar size and equal hemodynamic forces result in the occlusion in mammals but not in birds is consistent with the hypothesis that platelets mediate a more efficient clotting response than thrombocytes.

Dr. Kahn, the study’s senior author, concluded, “Although the reason for platelet evolution in mammals can never be known with certainty, it is tempting to speculate that platelets may have allowed early mammals to better survive trauma and thereby provided a survival advantage.”

The research was supported by National Institute of Health and by an American Heart Association (AHA) postdoctoral fellowship.

U.S. Population Weight Gain Increasing Further

In 2020, the vast majority of adults in America will be overweight or obese and more than half will suffer from diabetes or pre-diabetic conditions, according to projections presented by Northwestern Medicine researchers at the American Heart Association (AHA) Scientific Sessions, in Orlando, Fla.

The AHA has set a target to help Americans improve their overall heart health by 20% in 2020. However, if current trends continue, Americans can expect only a modest improvement of six percent in overall cardiovascular health in 2020.

The implications of not increasing heart health by 20% by 2020 could be grave. Declining rates of sickness and death from cardiovascular disease may stall, and related health care costs, already projected to reach $1.1 trillion per year by 2030, could rise even further. That’s according to study author Mark Huffman, MD, assistant professor in preventive medicine and medicine-cardiology at Northwestern University Feinberg School of Medicine and a cardiologist at Northwestern Memorial Hospital.

Representative of all Americans, the study is based on patterns found in the National Health and Nutrition Examination Surveys (NHANES) from 1988 to 2008. The projected numbers on weight and diabetes, based on previous trends, follow.

• In 2020, 83% of men and 72% of women will be overweight or obese.

Currently, 72% of men and 63% of women are overweight or obese (people who are overweight have a Body Mass Index (BMI) of 25 to 29kg/m2, people who are obese have a BMI of 30kg/m2 or greater).

• In 2020, 77% of men and 53% of women will have dysglycemia (either diabetes or pre-diabetes). Currently, 62% of men and 43% of women have dysglycemia.

“To increase overall heart health by 20%, American adults would need to rapidly reverse these unhealthy trends, starting today,” Huffman said. “In concert with individual choices, public health policies can be and should be effective tools to reduce smoking, increase access to healthy foods, and increase physical activity in daily life.”

More people would need to improve health behaviors related to diet, physical activity, body weight and smoking and health factors, related to glucose, cholesterol and blood pressure.

“We have been dealing with the obesity trend for the past three decades, but the impact we project on blood sugar is a true shock,” said Donald Lloyd-Jones, MD, chair and associate professor of preventive medicine at the Feinberg School of Medicine, a physician at Northwestern Memorial Hospital and senior author of the study. “Those are some really scary numbers. When blood sugar goes up like that, all of the complications of diabetes come into play.”

Less than five percent of Americans currently are considered to have ideal cardiovascular health. The modest six percent improvement in cardiovascular health that is projected for 2020 means better cholesterol and blood pressure numbers for Americans and fewer smokers. Improvements in treatment and control of cholesterol and blood pressure with medication and declines in smoking would partially account for this small boost, but they wouldn’t be enough to offset the weight and diabetes problems Americans face, Huffman said. Projected improvements in diet and physical activity also contribute to the six percent projection, but the absolute increase in Americans who consume ideal diets will remain less than two percent by 2020, if current trends continue.

“Since the 1960’s, cardiovascular disease death rates have substantially decreased, but if the weight and dysglycemia trends continue to increase, we are in danger of seeing a reversal of those gains,” Huffman said. Achieving a healthy weight through diet and physical activity is the best way most Americans can improve their cardiovascular health, but, as Huffman stressed, not smoking is the number-one preventable cause of preventable death. Yet one in five Americans still smoke.

The National Heart, Lung, and Blood Institute funded this study.

Withdrawal of Care Among Cardiac Arrest in Patients Treated with Therapeutic Hypothermia May Occur Too Soon

Patients Often Regain Consciousness Three Days or More After Arrest

Physicians may be making premature predictions about which patients are not likely to survive following cardiac arrest, and even withdrawing care, before the window in which comatose patients who have received therapeutic hypothermia are most likely to wake up, according to two new studies from the University of Pennsylvania. Patients treated with hypothermia often don’t regain consciousness until three or more days after their cardiac arrest, according to research at the American Heart Association’s annual meeting (abstract #10778). In a separate study published in Critical Care Medicine, a chart review found that documentation of “poor” or “grave” prognosis occurred early on in 57% of cardiac arrest patients’ treatment with hypothermia, with a quarter of those patients’ care being withdrawn within 72 hours after their arrest. More than 20% of those patients, whose doctors predicted they would die or suffer severe brain damage, survived to discharge with a good neurological outcome.

The study found that time to arousal following resuscitation and therapeutic hypothermia is highly variable and often >3 days. Of 154 patients studied in three hospitals over a five-year period, researchers found that 42% of patients studied survived to discharge from the hospital; 72% of those patients had a good neurological outcome. Mean time to arousal, which the researchers defined as the point at which the patient began following commands purposefully, was 3.8 days, with a range of 0.5 to 14.5 days. Even among those discharged in good neurological condition, the mean time to arousal was 3.2 days, indicating that efforts to predict a patient’s outcome early during cooling are not likely to be effective. Patients who had kidney problems prior to their arrest, had an initial heart rhythm that could not be shocked back to normalcy, and who did not receive paralytic drugs during their treatment were more likely to take longer to regain consciousness.