Angina Blog on Angina.com

Boston, MA— An article, published in Circulation by Laurel K. Leslie, MD, MPH from the Tufts Clinical and Translational Science Institute (CTSI) and colleagues from Tufts Medical Center and Floating Hospital for Children at Tufts Medical Center, has evaluated the lifesaving benefits and costs of screening programs for the prevention of sudden cardiac death (SCD) in children and adolescents. The authors found that screening can save lives, but that because it targets rare conditions and available tests have limited accuracy, screening for SCD is costly, compared to other life-saving measures.

Although rare, SCD often receives widespread attention because it is unexpected and can occur during childhood. Those factors have prompted many parents and policy makers to support screening programs. To help decision makers and the public understand whether more SCD screening is warranted, the authors, including collaborating clinical researchers from Children’s Hospital Boston, compared the potential life saving benefits (measured in terms of life years saved) to program costs. They considered two groups thought to be at elevated risk: school-aged children taking stimulants, which are often used to treat Attention Deficit Hyperactivity Disorder (ADHD), and adolescents playing organized sports. The research team determined that each year of life saved would cost from $90,000 (to screen adolescents before they participate in sports) to $200,000 (to screen children before they take ADHD medications).

Although there is no hard and fast line separating worthwhile and expensive public health interventions, programs can be compared to get an idea of their value. For example, interventions that cost $90,000 to $200,000 per life year saved are considered expensive, compared to other interventions, which often save life years at $50,000 to $100,000, or even less. The results of this study suggest that finite public health resources might be better spent elsewhere.

The “human cost” of screening suggests its true price may be even higher. Because conditions causing SCD are so rare, even an occasional “false positive” means that for every previously undiagnosed child accurately identified, many children who would never have died from SCD may be labeled as being at-risk.

The research team stressed that the cardiac conditions causing SCD in children are incredibly rare. Many are cardiac conditions are genetic and there may be a family history of early (< 50 years of age) or unexplained SCD in a family member. Dr. Leslie advises that “the most concerning family history in a child is when a parent or sibling is diagnosed with a likely familial cardiac disease; those children should certainly be evaluated.” Since some disorders that cause SCD may not be identifiable on an ECG until late adolescence or early adulthood, an ECG in a parent with a positive family history may provide more information than an ECG in a child. Another indication to consult with a doctor is if a child reports any experiences of fainting or shortness of breath with strong emotions or during exertion (not related to a medical condition like asthma).

STANFORD, Calif. — Pediatric cardiologists are prone to misinterpreting electrocardiograms when using the results to determine whether young athletes have heart defects that could make exercising perilous, according to a new study from the Stanford University School of Medicine and Lucile Packard Children’s Hospital. This is the first research to examine the acumen of pediatric cardiologists from several health-care institutions in using ECGs to detect rare heart conditions associated with sudden cardiac death.

Public outcries about sudden cardiac deaths among athletes have already prompted some European countries to require that young athletes undergo heart exams via ECG before they participate in sports. Even though the number of sudden cardiac deaths among young U.S. athletes is low — an estimated 76 per year —some people have suggested that athletes here should also receive mandatory ECGs so that those vulnerable to sudden cardiac death could be warned not to play sports.

Not so fast, say the authors of the new research.

“An ECG doesn’t always pick up the abnormalities that may predispose someone to sudden cardiac death,” said Allison Hill, MD, the study’s first author. “And this exam can be difficult to interpret, even if the person reading the scan is a pediatric cardiologist.” Hill recently finished her pediatric residency at Packard Children’s Hospital and is now a pediatric cardiology fellow at Children’s Hospital Boston.

An ECG exam uses electrodes attached to the chest and limbs to measure the electrical impulses generated as the heart beats. ECGs can detect heart rhythm abnormalities and other symptom-free heart conditions that could lead to sudden cardiac death.

In the new study, which will be published online July 14 in the Journal of Pediatrics, 53 members of the Western Society of Pediatric Cardiology were asked to interpret a set of 18 ECG exams, some from healthy athletes and some from those with heart defects. The physicians, who had an average of five to 15 years of experience in their field, accurately diagnosed the heart conditions only 67 percent of the time. They correctly permitted sport participation for healthy individuals 74 percent of the time, and correctly restricted sport participation for those with cardiac defects 81 percent of the time.

“As athletes’ hearts grow stronger, they undergo some changes that make it very difficult to tell: Is this a well-trained athlete or does this person have some underlying disorder that may predispose them to sudden cardiac death?” Hill said. A fit heart tends to grow somewhat larger and beat more slowly, which can make it look similar on an ECG to a defective heart vulnerable to sudden cardiac death. This similarity could lead to unnecessary exclusion of healthy young people from sport participation.

Conversely, some young athletes who are predisposed to sudden cardiac death may be given a clean bill of health based on a flawed ECG interpretation.

“We need to be careful about giving a false sense of security to families, parents or an entire community if we have an ECG that’s normal,” Hill said. “It’s important to know that it’s not a perfect test.”

The physicians’ accuracy at interpreting ECGs varied depending on what heart defect they were looking at. They were most accurate at picking up long QT syndrome and myocarditis, showing 98 percent and 90 percent accuracy at restricting sport participation for these two conditions. In contrast, they correctly restricted sport participation for patients with hypertrophic cardiomyopathy, Wolff-Parkinson-White syndrome and pulmonary arterial hypertension 80 percent, 64 percent and 38 percent of the time, respectively. (The poor result for pulmonary arterial hypertension may be due to the fact that it is much rarer than the other diagnoses, occurring in 30-50 people per million, whereas most of the other diagnoses are seen at a rates between one in 10,000 and one in 100 people.)

The new results dovetail with the current American Heart Association position on pre-sport ECGs, which recommends against routine use of the exams because of the large number of athletes in the United States, the low frequency of diseases leading to sudden cardiac death, the low rate of sudden cardiac death itself and the frequent false-positives that could unjustly exclude healthy individuals from sport participation. The AHA instead recommends a thorough history and physical exam every two years for young athletes.

A different Stanford study on ECGs for athletes, published in 2010, suggested ECGs for young athletes would be cost-effective. However, that study started from the assumption that ECGs would all be interpreted accurately, said cardiologist Euan Ashley, MD, who led the cost-effectiveness research.

If the United States does start instituting screening programs, Hill and her colleagues suggest that there is a need to ensure the physicians reading these ECGs are trained appropriately, which would add to the total load of information that pediatric cardiologists must already learn during their three-year training. It would also be important for physicians to use the proper normal values when evaluating these scans. Currently, there is not good consensus on what constitutes “normal” for a trained athlete’s heart, said co-author Anne Dubin MD, associate professor of pediatric cardiology, adding that data from such individuals exists but has not been widely shared.

When a high school athlete drops dead, the rare but fatal condition called “sudden death syndrome” dominates the headlines. For reasons that remain a mystery to scientists, some young athletes — especially young males — begin to experience an unusual heart arrhythmia. With over-exertion, their hearts stop pumping, leading to sudden death.

Until now, screening for the hard-to-detect syndrome has been prohibitively expensive. But cardiologist Dr. Sami Viskin of Tel Aviv University‘s Sackler Faculty of Medicine has developed a new test that’s already being used by doctors in America — and may have already saved lives.

The “Viskin Test” is based on the researcher’s discovery that almost imperceptible abnormalities between normal and at-risk patients could be suddenly be made more visible using a simple bedside test that requires a subject to suddenly stand up. When standing, at-risk patients will experience a measurable difference in a portion of their heart rate called the QT interval. The difference can be detected by an electrocardiogram (ECG).

Dr. Viskin described his research in a recent issue of the Journal of the American College of Cardiology.

The long and short of the QT test

“Current screening methods offer no real therapeutic value, because very few people who experience arrhythmias, up to 20 percent of the population, will ever die from sudden death,” Dr. Viskin says. “Moreover, there is such a significant overlap between what’s normal and abnormal on an ECG that we need additional screening parameters. This test, when done on people with strong symptoms, can really give us doctors a yardstick to compare those at risk for sudden death syndrome to those who would otherwise go on to live a healthy life.”

According to Dr. Viskin, the QT interval shortens when the heart rate accelerates, but this response is not instantaneous. In the study, he tested whether sudden changes in a body as it stands up would reveal an abnormally prolonged QT interval patients with long QT syndrome (LQTS), the most common cause of sudden death. Those affected with LQTS have a normal heart structure but have problems in the electrical discharge in the heart — they have trouble “recharging” after these sudden changes.

Young people who suddenly faint for no reason, have dizzy spells or have a family history of LQTS are very good potential candidates for this new test, Dr. Viskin says.

A warning for immediate intervention

In the study that led to the “Viskin Test,” Dr. Viskin assessed 68 patients with LQTS and 82 control subjects who all underwent a baseline ECG while resting in the supine position. They were then asked to get up quickly and stand still during continuous ECG recording. The QT interval was then studied over various time periods.

In response to brisk standing, both the LQTS patients and the control subjects showed similar heart rate acceleration. But Dr. Viskin discovered that the QT interval in LQTS patients increased significantly.

“This test adds diagnostic value. And the beauty of the test,” Dr. Viskin adds, “is that it’s easily done at the patient’s bedside. It eliminates the need for more expensive IV tests and more strenuous exercise tests.”

He adds that, while untreated LQTS can be life-threatening, the therapies to treat it can be very effective.

The way the heart responds to an early beat is predictive of cardiac death, especially for people with no conventional markers of cardiovascular disease, according to new research from Washington University School of Medicine in St. Louis.

The conventional risk factors, such as high cholesterol, smoking, diabetes and high blood pressure, account for many but not all deaths from cardiovascular causes. As a result, doctors are always searching for better ways to identify patients at risk of cardiac death.

The new research indicates that an abnormal response to an early beat in the left ventricle, the heart’s main pumping chamber, can identify high-risk patients even when they have no other evidence of cardiovascular disease.

The work appears Feb. 15 in the Journal of Cardiovascular Electrophysiology.

A ventricular premature beat (VPB) occurs when the ventricle gets an inappropriate signal causing it to beat before it should. VPBs are common, even in healthy people. The question is not whether VPBs occur, but how the body responds to them. The heart’s response to a VPB is called heart rate turbulence. It can be measured with a Holter monitor, a device worn for 24 hours that records a person’s electrocardiogram, the electrical signals produced by the heart.

When the ventricle beats early, the heart has not finished filling and it pumps less blood to the body than it should. To compensate, the heart rate speeds up to increase blood flow.

But an early beat also empties the heart early, leaving extra filling time afterward. So on the second beat after the VPB, the heart is extra full and pumps more blood to the body than it should. To compensate properly, the heart rate slows down.

A healthy heart will alternately speed up and slow down to compensate for the over- and under-filling that follows a VPB until the amount of blood filling the heart returns to normal.

Abnormal heart rate turbulence occurs when the heart can’t compensate in this way.

“It’s a clear test of whether the autonomic nervous system, which regulates your heart rate, can adapt to a challenge,” Stein says.

Stein and colleagues analyzed Holter monitor recordings for almost 1,300 patients over age 65 recorded between 1989 and 1993.

The patients were divided into three groups based on an assessment of their cardiovascular health. Those in the “clinical” group had a history of cardiovascular disease such as heart attack or surgery to open narrow blood vessels. Those in the “subclinical” group had traditional risk factors for cardiovascular disease such as high blood pressure or diabetes but had never been treated for cardiovascular disease. And those in the “healthy” group had no evidence of clinical or subclinical disease.

In all three groups, abnormal heart rate turbulence was predictive of cardiac death. But the association was especially strong in the healthy group. Of the 357 patients classified as healthy, 21 had abnormal heart rate turbulence. These 21 people were almost eight times more likely to die of cardiac causes than the rest of the healthy group.

“Even though it’s a small group of people, they’re actually at very high risk,” Stein says.

In fact, over the next 12 years, the people in the healthy group with abnormal heart rate turbulence had worse survival than the people with subclinical disease but good heart rate turbulence.

“They’re actually not healthy,” Stein says. “Something is wrong. But the conventional risk factors don’t pick it up.”

Stein and her colleagues also looked at levels of C-reactive protein, a measure of inflammation associated with cardiovascular disease. While C-reactive protein predicted cardiac death in the healthy group, it had no impact in the subclinical and clinical groups. Since heart rate turbulence was predictive in all three groups, it may prove better than C-reactive protein in predicting risk of cardiovascular death.

Though the Holter monitor is a common, noninvasive device, Stein says the software needed to measure heart rate turbulence is only available for clinical use on one commercial Holter monitor. She speculates that this work and other studies showing the value of measuring heart rate turbulence may make the software more widely available.

This work was supported by the National Heart, Lung, and Blood Institute and the National Institute of Neurological Disorders and Stroke.

Researchers identify the genotype of disorders causing cardiac
sudden death syndrome   2011-02-08 12:16:00

Long QT syndrome approximately affects one in every 2,500 people ­-mainly young people. It can cause to
rsade de pointes episodes , which can trigger sudden death. This study was conducted by researchers of the Hospital Virgen de las Nieves of the University of Granada . The genetic analyses were performed by the laboratory Lorgen in the Health Science Technology Park of Granada.

Researchers from the Hospital Virgen de las Nieves of the University of Granada have identified the most
frequent mutations in the gene KCNH2 in patients with long QT syndrome.

Long Qt syndrome is a disorder of cardiac ionic channels that approximately affects one in every 2,500 people and
may cause torsade de pointes episodes, which can trigger sudden death. This condition usually affects children
and adolescents, and it is occasionally mistaken for convulsions, leading to a misdiagnosis of epilepsy.

So far, hundreds of mutations have been found in twelve genes of sodium and potassium channels. Thus,
approximately 75% of the mutations in cases of LQTS are located in three genes: KCNQ1, the most frequent in
other sectors of the population (potassium channel), KCNH2 (potassium channel) and SCN5A (sodium channel).

To carry out this study, researchers selected nine patients who met the diagnostic criteria for long QT syndrome,
and four patients with ventricular fibrillation (cardiac arrest produced in the absence of any identifiable causes).
These patients and their first-degree relatives were examined in the Arrhythmia Assessment Unit of the Hospital
Virgen de las Nieves in Granada, Spain.

Genetic Study

Mutations were found in seven patients with long QT syndrome and in two patients with idiopathic ventricular
fibrillation. Overall, 71.4% of mutations were in the gene KCNH2 and 28.6% were in SCN5A. No mutations were
found in the gene KCNQ1. Only two mutations had been previously observed.

In fact, one of these mutations was studied in vitro, and their involvement in the etiology of the disease was
definitely proved, which is a major contribution to this field of research (see picture). This test was conducted with
the collaboration of the Department of Pharmacology of the Universidad Complutense of Madrid.

Of the 19 relatives studied, six were carriers of the mutation. Unlike previous studies, the study conducted in
Granada proved that genetic testing had a high level of sensitivity for the diagnosis of patients with long QT
syndrome, and that the most frequently mutated gene was KCNQ1. These results differ from the results obtained in
studies with other populations, where the most frequently mutated gene was KCNQ1.

This study -published in the Revista Española de Cardiología- was conducted by Juan Jiménez Jáimez, Luis
Tercedor Sánchez, Miguel Álvarez López, Ricardo Sebastián Galdeano
(Hospital Virgen de las Nieves), Esther Martínez Espín and José Antonio Lorente Acosta
(Department of Legal Medicine and Toxicology of the University of Granada ). Genetic analysis was performed at the Laboratory of Genetic Analysis Lorgen in Granada PTS.

“What it is important about this study is that it proves that genetic testing can help in diagnosing LQTS in patients
without any phenotypic expression, that is, in patients with normal results in electrocardiogram and medical
imaging tests” –researchers state. “This increases the chances of detecting relatives who may be carriers of the
same disease but who obtain inconclusive results in other tests, which represents an important breakthrough, since
these genetic diseases can be hereditary”.

Although the results obtained are of great significance, the researchers warn about the fact that “this study is just
an initial experience in our country, and it only describes the genotypic profile of a small sample of patients.
A multicenter study will be necessary to obtain larger groups and draw conclusions that can be extrapolated to the
general population” –researchers state.