Detecting deadly aortic aneurysms

A new key to detecting deadly aortic aneurysms

October 25, 2007 - New Haven, Conn.-Yale scientists have discovered a way to use a simple blood test that may accurately detect thoracic aneurysm disease (TAA), which gives little warning and is almost always fatal if untreated.

The study, published this month in Public Library of Science (PLoS), represents the collaborative work of Yale School of Medicine, Applied Biosystems, and Celera Diagnostics.

TAAs occur in the part of the aorta that passes through the chest. They can become huge without causing symptoms. In fact, only one in 20 patients has symptoms before internal rupture occurs-making advance detection key to treatment. Once the aneurysm ruptures, a person can go into shock and die from internal bleeding. Currently detection of these aneurysms is made by relatively expensive tests such as a chest X-ray or CT scan-typically when a patient is being evaluated for other conditions.

"A standardized blood-based test capable of detecting individuals at risk for aneurysm disease would represent a major advance in clinical care," said John Elefteriades, M.D., section chief of cardiothoracic surgery. "This study indicates we may be able to develop such a test."

In this study Elefteriades and his colleagues took blood samples from 58 persons diagnosed with TAA disease and 36 spouses who did not have the disease. Using a gene expression profiling technology, they identified a 41-gene signature in blood cells that distinguishes TAA patients from those without the disease. The gene expression signature and the prediction model were identified using a complete workflow of instruments, reagents, and software from Applied Biosystems. These signature genes were further validated using TaqMan® real-time PCR assays. The accuracy rate in various analyses is 78 percent to 85 percent.

"It has become increasingly evident that the immune system plays a pivotal role in the development of aortic aneurysms," Elefteriades said. "We thus hypothesized that gene expression patterns in peripheral blood cells may reflect TAA disease status."

The next step, which the researchers say is underway, is validation in real-time clinical studies. The investigative team is also interested in determining if abdominal aneurysms share a similar RNA signature, and if the RNA can predict rupture or dissection of an aneurysm.

Yale University
http://www.brightsurf.com/news/headlines/33844/A_new_key_to_detecting_deadly_aortic_aneurysms.html

Early signs of heart disease

Obese children show early signs of heart disease

Children who are obese or who are at risk for obesity show early signs of heart disease similar to obese adults with heart disease, a study by researchers at Washington University School of Medicine in St. Louis has found.

"Based on this study, these subtle markers can help us predict who could be at risk for heart disease and heart attacks," said Angela Sharkey, M.D., associate professor of pediatrics at Washington University School of Medicine and a pediatric cardiologist at St. Louis Children's Hospital.

The study was published in the Winter 2007 issue of the Journal of Cardiometabolic Syndrome.

Childhood obesity in the United States is an epidemic - nationwide, 19 percent of children ages 6 to 11 and 17 percent of those 12 to 19 are overweight, according to the Centers for Disease Control and Prevention (CDC). Those who are overweight during childhood also have an increased risk of obesity in adulthood and are at greater risk for complications such as diabetes, high blood pressure and heart disease, because obesity increases total blood volume, which leads to extra stress on the heart.

Sharkey and Steven M. Lorch, M.D., a former fellow at the School of Medicine now at University of Texas Health Science Center at Houston, analyzed data from 168 children ages 10 to 18 who had been referred to them for cardiac ultrasound with symptoms including heart murmur, chest pain, acid reflux or high blood cholesterol. Based on CDC guidelines for body mass index for age (BMIA), 33 patients were found to have a BMIA as obese, or the 95th percentile or above for their age; 20 had a BMIA that classified them as at risk for obesity, or between the 85th and 94th percentile; and 115 were considered normal, or below the 85th percentile.

To analyze the hearts of the obese children and those at risk, Sharkey and Lorch used a new tissue Doppler imaging technique called vector velocity imaging which tracks the movement of the heart's muscular wall. Any changes in the rate of motion of heart muscle were averaged within each group and compared to the normal rate of motion.

"In the patients who are obese, the rate of motion of heart muscle changed," Sharkey said. "As a child's BMIA increases, we see alterations in both the relaxation and contraction phase of the heartbeat. Many of these changes that have been seen in adults were assumed to be from long-standing obesity, but it may be that these changes start much earlier in life than we thought."

As vector velocity imaging becomes more broadly available, Sharkey said, it could potentially help pediatric cardiologists follow these children more closely over time to see if changes in the heart progress.

"We may be able to determine whether we could intervene in the process, such as focusing the families on understanding the importance of regular exercise and dietary modifications for weight loss and prescribing statin drugs for high-blood cholesterol," she said.

Sharkey said the results of the study give more ammunition to physicians to use in counseling pediatric patients and their parents about the risks of obesity and the need to attain a healthy weight.
"Even in teenagers, obesity leads to decreased myocardial performance and abnormal diastolic function," she said.
Further study is needed to determine how soon the changes in the heart set in after a child becomes obese and whether those changes are reversible with weight loss.

Washington University School of Medicine
http://www.brightsurf.com/news/

Sudden Cardiac Death - Genetic investigations

Contribution of Inherited Heart Disease to Sudden Cardiac Death in Childhood

Nynke Hofman, MS (a), Hanno L. Tan, MD, PhD (b), Sally-Ann Clur, MD (c), Mariel Alders, PhD (d), Irene M. van Langen, MD, PhD (a) and Arthur A. M. Wilde, MD, PhD (b)
a ) Departments of Clinical Genetics; b)  Cardiology; c) Pediatric Cardiology; d)  Molecular Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

BACKGROUND. In children aged 1 to 18 years, the causes of sudden cardiac death may remain unresolved when autopsy results are negative. Because inherited cardiac diseases are likely, cardiologic and genetic investigations of relatives may still yield the diagnosis in these cases. Moreover, these investigations provide timely identification of relatives who are also at risk of sudden cardiac death. We aimed to establish the cause of sudden cardiac death in the children of whom the family was referred to our cardiogenetics department and the diagnostic yield of these investigations.

METHODS AND RESULTS. We genetically counseled 25 consecutive, unrelated families after sudden cardiac death of a child (aged 1 to 18 years) who was disease-free during lifetime and in whose family there was no known inherited heart disease. We performed cardiac investigation (electrocardiography, exercise testing, and echocardiography) of first-degree and second-degree relatives and performed diagnosis-directed DNA analysis. Autopsy was performed in 20 case subjects. A diagnosis was identified in 14 of 25 families. In addition, we studied 10 children after aborted sudden cardiac death; in 6 of them, a diagnosis was made. Overall, in 17 of the 19 families in whom an inherited disease was diagnosed, a disease-causing mutation in either a first-degree relative or the index patient confirmed the diagnosis.

CONCLUSIONS. Sudden cardiac death in children seems to be caused often by inherited cardiac diseases. Cardiac and genetic examination of relatives combined, if possible, with postmortem analysis after sudden cardiac death of a child has a high diagnostic yield (14 of 25), comparable to analysis in surviving victims of sudden cardiac death (6 of 10). Because sudden cardiac death can be prevented by timely treatment, these results warrant active family screening after unexplained sudden cardiac death of a child.

Key Words: sudden cardiac death • children • molecular genetics • arrhythmia • genetic counseling

http://pediatrics.aappublications.org/cgi/content/abstract/120/4/e967
PEDIATRICS Vol. 120 No. 4 October 2007, pp. e967-e973
© 2007 American Academy of Pediatrics.

Myocardial infarction occurs in children

Myocardial Infarction in Healthy Adolescents

John R. Lane, MD and Giora Ben-Shachar, MD
The Heart Center, Akron Children's Hospital, Akron, Ohio

OBJECTIVE. Chest pain in children and adolescents is a frequent cause for office or emergency department visits. However, it is unclear whether myocardial infarction occurs in children with no anatomic abnormality presenting with chest pain.

METHODS. Clinical history, electrocardiography, echocardiography, and cardiac enzyme levels were evaluated in patients presenting to the emergency department over a period of 11 years (June 1995 to May 2006). Patients in whom findings were suggestive of acute myocardial infarction, in addition, underwent drug screening, serum lipid profile, and hypercoagulability workup and, when myocardial infarction was diagnosed, heart catheterization with coronary angiography.

RESULTS. Nine patients (8 boys; age range: 12–20 years; mean: 15.5 years) met established criteria for myocardial infarction. Abnormal electrocardiograms were found in 8 patients (6 with ST elevation and 2 with nonspecific ST-T abnormalities), abnormal cardiac enzyme levels in all, and echocardiographic abnormalities in 3. Cardiac dysrhythmias were found in 4 patients, 3 with nonsustained ventricular tachycardia. Drug abuse, lipid profile, and hypercoagulability studies were negative in all. Left ventricular focal hypokinesia was seen by echocardiogram or angiography in 5 patients and abnormal coronary anatomy in none. Cardiac function normalized in 8 patients. One patient had a persistent focal inferior hypokinesis. Calcium channel blocker therapy was initiated in all of the patients with no recurrence of anginal chest pain on follow-up. One patient complained of chest pain distinct from anginal pain.

CONCLUSIONS. Myocardial infarction can occur in adolescents with normal coronary arterial anatomy. Adolescents who present for emergency care with typical chest pain need electrocardiographic and cardiac enzyme workups. Those with results that are suggestive of acute infarction require additional workup. Coronary vasodilation therapy seems helpful, but given the lack of coronary thrombosis in these patients, thrombolytic therapy seems unwarranted. Long-term follow-up is necessary, and adjustments in therapy may be required with time.

PEDIATRICS Vol. 120 No. 4 October 2007, pp. e938-e943
http://pediatrics.aappublications.org/cgi/content/abstract/120/4/e938

High blood pressure in the Children

We usually think of high blood pressure, or hypertension, as a problem that affects adults. But, in fact, this condition can be present at any age, even in infancy. About five of every hundred children have higher than normal blood pressure, although fewer than one in a hundred has medically significant hypertension.

How blood pressure is measured

The term blood pressure actually refers to two separate measurements:

• systolic blood pressure is the highest pressure reached in the arteries as the heart pumps blood out for circulation through the body
  

• diastolic blood pressure is the much lower pressure that occurs in the arteries when the heart relaxes to take blood in between beats
  

If either or both of these measurements are above the range found in healthy individuals of similar age and sex, it’s called hypertension.

Who gets high blood pressure

• Hypertension is more common among individuals of color than whites. It also seems to be more prevalent in some parts of the world; for example, it’s very rare among Alaskan Inuit, but affects as many as forty of every hundred adults in northern Japan.
  

• In many cases hypertension seems to develop with age. As a result, your child may show no signs of high blood pressure as an infant, but may develop the condition as she grows.
  

• Youngsters who are overweight are also more prone to have hypertension (and other chronic diseases). Thus good eating habits (without overeating and without emphasizing high-fat foods) and plenty of physical activity are important throughout the early years of childhood (and for the rest of her life).
  

http://www.aap.org