Physical examinations can provide critical information unavailable by other means to help patients experiencing urgent cardiac care issues, such as heart attack or unstable chest pain, according to research conducted at the Cleveland Clinic (Cleveland, Ohio). Data from such exams including Killip classification are important in predicting all-cause mortality for acute coronary syndrome (ACS) patients at intervals of 30 days and six months, the researchers said. Killip classification grades the severity of acute and chronic heart failure by assigning a level of I to IV I indicating no evidence of heart failure, IV indicating cardiogenic shock in which the heart is unable to supply sufficient blood to the body.

Though some have questioned whether increasingly sophisticated tests have reduced the relevance of physical exams, this study indicates otherwise, said Eric Topol, MD, chairman of cardiovascular medicine at the Cleveland Clinic. "It's back to basics in the assessment and treatment of patients with acute coronary syndromes." Topol said. "The physical exam is crucial in understanding the patient's level of risk." For the study, the clinic analyzed data from more than 26,000 patients and four national trials that recorded Killip classification and other physical data, measuring the association between Killip classification and all-cause mortality at 30 days and six months. In addition to Killip classification, researchers studied age, heart rate, systolic blood pressure and body mass index.

According to the study, patients with heart failure (Killip II, III and IV) were older and sicker than those without. They also were more likely to have diabetes, previous heart attack or heart failure, lung disease, kidney disease and prior stroke. Class I was used as a benchmark. Physical exams of Class I patients revealed higher heart rates and lower blood pressures. Patients with more severe heart failure as determined by Killip class were determined to be at greater risk of death at both 30-day and six-month intervals. Class II patients (some evidence of heart failure) were at three times greater risk of dying within 30 days than were Class I patients. Patients in Class III (pulmonary edema) and Class IV (cardiogenic shock) were at more than five times greater risk of dying within 30 days than were their Class I counterparts.

Researchers concluded the severity of heart failure as determined by Killip classification was more closely associated with the risk of death than heart attack. Complete study results appeared in the Oct. 22 issue of the Journal of the American Medical Association.

Lupus transmission and heart disease

A new study may shed light on why some infants born to women who produce antibodies commonly found in lupus patients develop an autoimmune disease that can cause permanent heart damage. The study, published in the Nov. 15 issue of The Lancet and led by Dr. Anne Stevens, a researcher at Fred Hutchinson Cancer Research Center (Seattle, Washington), looked at infants who died of heart block, a particularly severe form of the disease, known as neonatal lupus syndrome. Stevens and colleagues at the University of Washington (also Seattle) and the Hospital for Joint Diseases (New York) found that each newborn's heart was partly made up of cells from their mother that had transferred during pregnancy.

The study is the first to show that circulating cells from the mother which the scientists suspect to be stem cells that normally regenerate only blood tissue can migrate to the heart, where they develop into heart muscle. The researchers said they do not yet know whether the maternal cells trigger a destructive immune response by the unborn fetus, leading to heart inflammation, or whether the maternal cells migrate to the heart in an attempt to repair existing damage. "We don't know if the maternal cells are harmful or helpful in these infants," said Stevens, a research associate in the laboratory of Dr. Lee Nelson at Fred Hutchinson. "Maternal cells routinely pass into the fetus during pregnancy, and in most cases cause no harm."

Stevens said that what needs to be determined next "is whether in fact these cells actually contribute to the onset of this disease and, if so, under what circumstances, since some exposed to these antibodies are totally healthy without any heart problems. If babies with this condition have few or no symptoms and many mothers predisposed to give birth to babies with the syndrome have healthy babies. If we can answer these questions, it may help us to develop a way to intervene in order to prevent damage to the baby's heart."

Like other autoimmune diseases, neonatal lupus syndrome is caused by an inappropriate reaction of the immune system against the tissue of one or multiple organs in a person's own body. The syndrome is the most common of three autoimmune diseases known to affect newborns, and symptoms can range from mild rashes that disappear shortly after birth to severe heart damage that results from inflammation and scarring. About one-fifth of these infants whose disease affects the heart die of the syndrome, while the other two-thirds live normal lives with pacemakers that are inserted shortly after birth or later in life.

To determine whether maternal cells might play a role in neonatal lupus syndrome, the researchers identified four male infants that had died prior to or shortly after birth from heart damage and whose mothers produced anti-Ro and anti-La antibodies. They also identified four control infants who had died of other causes. Male infants were chosen so that maternally derived cells, which contain two X chromosomes, could be easily distinguished from the infant cells, which have one X and one Y chromosome.

Researchers found maternal cells in 15 of 15 tissue sections of the heart from babies who had died of the autoimmune disease but only in two of eight sections from the control infants. The maternal cells were present at much higher levels in the neonatal lupus hearts than in controls. Most of the maternal cells produced proteins characteristic of heart muscle.

According to Stevens, it is not yet known how the maternal cells came to be incorporated into the fetal hearts. "The cells that pass from mother to fetus are assumed to be circulating cells, which are presumably blood cells," said Stevens. "We think that the cells that are developing into heart tissue are hematopoietic stem cells, which normally give rise to immune-system cells." Previous work from Nelson's laboratory has found an association between the autoimmune disease scleroderma and the presence of trace fetal cells that persist in women who have borne children as well as women and men who harbor cells from their own mothers. Neonatal lupus syndrome can develop in the unborn children of women whose immune systems produce two antibodies called anti-Ro and anti-La which react against two proteins found in the cells of all individuals.

Although women with lupus as well as those who suffer from another autoimmune disorder known as Sjogren's syndrome produce the two antibodies, they can also be found in women with no symptoms, but may develop it later in life. The anti-Ro and anti-La factors can pass from the mother to the fetus, although the presence of the antibodies alone, in either the mother or fetus, is not sufficient to trigger disease in the unborn child. Only 2% of the women with the antibodies give birth to babies with heart block. The percentage for skin rash may be similar, but is unknown.

Stevens' study is the first to demonstrate that circulating maternal cells during pregnancy can reconstitute heart tissue in the fetus. Stevens said that if the maternal cells are what provoke a harmful immune response from the fetus, researchers may someday be able to block the damage by creating antibodies that target and destroy the maternal cells before the baby's immune system can mount a response.

To further analyze the onset of neonatal lupus syndrome, Stevens is now conducting a study of twins and triplets in which only one of the siblings develops the disease as well as examining whether other organ systems besides the heart may be affected.

Stevens said that it is a great scientific mystery as to why there is so much cell circulation between mother and fetus. "It may be that the passage of cells helps to prime the baby's immune system-which would be a beneficial event," she said. "But for reasons we still have yet to discover, in some individuals, it may cause disease."

Program pushes beta blockers

Heart attack survivors generally put the chance of another heart attack among the list of greatest fears, and about 450,000 heart attacks, among the 1.1 million reported each year, are recurrences. But many of the 7.5 million heart attack survivors in the U.S. don't follow one of the simplest steps to live longer and help prevent a recurrence: taking a prescription beta blocker for life. Large-scale clinical trials have proven that taking a beta blocker every day for life after a heart attack can cut the risk of another heart attack and death by up to 40%.

To address this issue, the more than 20 member health plans and networks of the Council for Affordable Quality Healthcare (CAQH) are joining forces in a public education campaign called heartBBEAT for life (Beta Blocker Education and Treatment), developed in collaboration with the American Heart Association (AHA), the American College of Cardiology (ACC), the American Academy of Family Physicians, the American College of Physicians and the AHRQ-sponsored Duke University Center for Education and Research on Therapeutics. heartBBEAT for life seeks to educate heart attack survivors, their caregivers and physicians about the long-term benefits of beta blockers.

Richard Snyder, MD, co-chair of heartBBEAT for life and vice president of quality management with Independence Blue Cross, said, "Given the likelihood of a heart attack recurrence, it is incredibly important for survivors to make physical, lifestyle and medical changes to protect the future health of their hearts. Taking beta blockers is one of the easiest ways to prevent another heart attack, which is why we want more people to be aware of their benefits ... [O]ur goal is to encourage heart attack survivors to talk to their doctors about getting on and staying on these important medicines for life."

The State of Health Care Quality, published by the National Council for Quality Assurance (NCQA), reports that more than 90% of heart attack patients are prescribed a beta blocker within seven days of leaving the hospital. That percentage has risen steadily since NCQA began tracking the measure in 1999, credited largely to cardiac treatment guidelines developed jointly by the ACC and the AHA, as well as to public reporting.