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Echo study at the Children’s Hospital of Philadelphia shows improvements in children, young adults with single ventricle

Sildenafil, also known as the erectile dysfunction drug Viagra, may give a boost to underdeveloped hearts in children and young adults with congenital heart defects. Researchers from The Children’s Hospital of Philadelphia report that sildenafil significantly improved echocardiographic measures of heart function in children and young adult survivors of single ventricle heart disease palliation.

“Although researchers will need to evaluate clinical benefits over a longer period with a larger number of patients, this finding offers a potential advance in the management of patients with these types of heart defects,” said study leader David J. Goldberg, M.D., a pediatric cardiologist at The Children’s Hospital of Philadelphia.

The study appeared online recently in the journal Pediatric Cardiology.

The researchers randomly assigned 27 children and young adults at Children’s Hospital to receive either sildenafil or a placebo for six weeks. After a six-week break in treatment, the subjects were switched to the opposite treatment course. The study team used echocardiograms to measure myocardial performance index (MPI), an indicator of the heart’s overall ability to pump blood.

The patients in this double-blind, short-term study, who had a mean age of 14.9 years, had undergone a Fontan operation in early childhood, a mean of 11.3 years previously. The Fontan surgery redirects blood circulation in patients born with a severely underdeveloped ventricle, one of the heart’s two pumping chambers. The operation is the third in a staged series of surgeries for life-threatening single-ventricle defects.

Although surgical advances over the past 20 years have dramatically improved survival for single-ventricle defects, patients with the condition continue to have long-term illness and risk of early death. The staged surgeries do not recreate normal heart circulation, but instead redirect blood flowing from the veins directly to the lungs, bypassing the heart. However, blood vessels in the lungs develop resistance to this blood, often reducing a patient’s ability to tolerate exercise.

Sildenafil, which reduces blood vessel resistance to the flow of blood, is already used to treat pulmonary hypertension (high blood press in lung vessels), as well as erectile dysfunction. Because sildenafil has also shown promise as a treatment for adults with heart failure, the Children’s Hospital researchers are exploring whether it may benefit younger patients with certain types of congenital heart disease.

The current study is part of a broader phase 2 clinical trial at The Children’s Hospital of Philadelphia, the Sildenafil After the Fontan Operation (SAFO) trial. A previous study from the same research team, published in March 2011, found improvements in exercise performance, as measured by ventilator efficiency, in children and young adults with single-ventricle disease who took sildenafil compared to those who took placebo.

The current study was the first to show that sildenafil improved echocardiographic measures of ventricular performance in children and young adults with single-ventricle physiology. The biological mechanisms that affect ventricular performance are not fully understood, said Goldberg, but he noted that studies in other patients with heart disease suggest that inhibiting the abnormally high levels of the enzyme phosphodiesterase E5 (PDE5) may produce the physiological benefits seen in the single-ventricle patients.

Goldberg cautioned that further research should be pursued to determine if the observed improvements in ventricular performance persist beyond the short term and if they provide clear quality-of-life benefits. “If sildenafil is safe over the medium and long-term, and if it produces durable functional improvements, patients with single-ventricle heart disease could have their first effective long-term treatment,” he added.

Goldberg’s co-authors were Anita L. Szwast, M.D., Michael G. McBride, Ph.D., Nicole Mirarchi, M.A., Brian D. Hanna, M.D., Ph.D., Gil Wernovsky, M.D., and Jack Rychik, M.D., all from Children’s Hospital; Benjamin French, Ph.D., from the Perelman School of Medicine of the University of Pennsylvania; and Bradley S. Marino, M.D., MSCE, of Cincinnati Children’s Hospital Medical Center.

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).

New study shows fortified “doogh” improves inflammatory markers in patients with type 2 diabetes

Newswise — Chevy Chase, MD— Daily intake of vitamin D-fortified doogh (Persian yogurt drink) improved inflammatory markers in type 2 diabetics and extra calcium conferred additional anti-inflammatory benefits, according to a recent study accepted for publication in The Endocrine Society’sJournal of Clinical Endocrinology and Metabolism (JCEM).

Inflammation is known to have a central role in the development of type 2 diabetes and its further complications like coronary heart disease and stroke. Vitamin D carries benefits for skeletal health but evidence of an anti-inflammatory effect from clinical studies in humans remains scarce.

“Our previous research showed that improvement of vitamin D status by regular daily intake of a fortified yogurt drink resulted in lowered blood glucose levels in diabetic patients,” said Tirang Neyestani, PhD, of Shahid Beheshti University of Medical Sciences in Tehran, Iran and lead author of the study. “The current study found that consuming a vitamin D-fortified yogurt drink also decreased serum substances like highly sensitive C-reactive protein (hsCRP) which are known to have an inflammatory role.”

In this study, researchers conducted a double-blind, randomized, controlled trial over 12 weeks in 90 patients with type 2 diabetes. Study participants were randomly allocated to one of three groups to receive two 250mL bottles a day of either plain doogh, vitamin D-fortified doogh or calcium plus vitamin D-fortified doogh. Vitamin D levels, insulin resistance, and inflammatory markers such as hsCRP, fibrinogen and adiponectin were measured in blood samples taken from study participants.

“Our study showed for the first time that adiponectin, a substance secreted by fat tissue that has an anti-inflammatory effect, increased when calcium and vitamin D-fortified doogh was consumed,” said Neyestani. “Our findings may offer interesting therapeutic options for diabetic patients.”

Other researchers working on the study include: Bahareh Nikooyeh, Hamid Alavi-Majd, Nastaran, Shariatzadeh, Ali Kalayi, Nima Tayebinejad, Soudabeh Heravifard, Shabnam Salekzamani and Malihe Zahedirad, all with Shahid Beheshti University of Medical Sciences.

The article, “Improvement of vitamin D status via daily intake of fortified yogurt drink either with or without extra calcium ameliorates systemic inflammatory biomarkers, including adipokines, in the subjects with type 2 diabetes,” appears in the June 2012 issue of JCEM.

New Rochelle, NY, July 29, 2011–Intravenous delivery of cold fluids to reduce body temperature quickly after a heart attack and improve neurologic outcomes may not be as effective in children as it is in adults, according to a study reported in Therapeutic Hypothermia and Temperature Management, a peer-reviewed journal published by Mary Ann Liebert, Inc. The article is available free online at www.liebertpub.com/ther

In adults, therapeutic hypothermia to minimize neurological complications caused by cardiac arrest can be achieved by rapidly infusing cold (4oC) intravenous fluid. However, this might not be the optimal approach in children. Alexis Topjian, Michael Hamid, Larissa Hutchins, and Vinay Nadkarni, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, studied the effect of the infusion rate on the temperature of the cold IV fluid in three simulated pediatric patients of different weights. They describe the study design and their results in the article entitled, “Can a Cold (4oC) IV Fluid Bolus to Induce Therapeutic Hypothermia Really Deliver 4oC to Children?”

“This is an important and timely contribution because it reinforces the point that children are not just small people but require specialized treatment strategies to target pediatric CNS injury,” says Editor-in-Chief W. Dalton Dietrich, PhD, Kinetic Concepts Distinguished Chair in Neurosurgery, Professor of Neurological Surgery, Neurology and Cell Biology and Anatomy, University of Miami Leonard M. Miller School of Medicine.

A program to educate students about heart-healthy lifestyles resulted in significant improvements in middle school students’ cholesterol levels and resting heart rates, including four years of follow-up.

Students continued to experience health benefits, make better food choices and participate in physical activities after the intervention, suggesting that such a program could decrease cardiovascular disease and diabetes risks

WASHINGTON, May 13, 2011 /PRNewswire-USNewswire/ — Middle school students who were offered healthier cafeteria food, more physical education and lessons about health choices improved their cholesterol levels and resting heart rates, according to research presented at the American Heart Association’s Quality of Care and Outcomes Research 2011 Scientific Sessions.

“This four-year school intervention in Ann Arbor, Mich., was designed to promote healthier lifestyle choices and it shows that programs like this could have long-term impact on obesity and other health risks,” said Elizabeth A. Jackson, M.D., M.P.H., co-author of the study and assistant professor of internal medicine at the University of Michigan. “Such changes may have sustained benefits in terms of reducing incidences of diabetes and cardiovascular disease as the students age.”

The intervention was conducted through Project Healthy Schools, a coalition of the University of Michigan and local community and business organizations working to improve the health and behavior choices of middle school students. It was considered so successful that it’s now being expanded to about 20 middle schools in Michigan, Jackson said.

Specifically, the program goals for the students included:

• Eating more fruits and vegetables;
• Eating less fatty foods;
• Making better beverage choices;
• Getting at least 150 minutes of physical activity each week; and
• Spending less time in front of the TV and computer.

To help determine whether the initiative could decrease future cardiovascular disease and diabetes risks, Jackson and colleagues studied 593 students. They collected data for four consecutive years on body mass index, cholesterol levels, blood pressure, heart rate and student self-evaluations of diet, exercise and other behaviors.

“Results of the wellness survey indicate that, after four years, students continued to make health-conscious decisions,” Jackson said.

The researchers report:

• Average cholesterol, which was 167.39 milligrams per deciliter of blood (mg/dL) at the start of the study, was an average of 149.04 mg/dL at the end of four years.
• Low density lipoprotein (LDL) was an average 92.02 mg/dL at the study’s start, versus 85.88 after four years.
• Resting heart rate (beats per minute) was an average 81.3 compared to 78.3 after four years.

A limitation of the study is that it does not compare students in the program to similar groups not participating. Such a comparison study would be the next step in determining an association between initiative participation and health benefits, Jackson said.

Co-authors are Nicole L. Corriveau, B.S.; Roopa Gurm, M.S.; Caren S. Goldberg, M.D.; Jean DuRussel-Weston, R.N., M.P.H.; Taylor F. Eagle; Lindsey Gakeheimer; LaVaughn Palma-Davis, M.A.; Susan Aaronsonl, R.D., M.A.; Catherine M Fitzgerald, R.D., M.A.; Lindsey Mitchell, M.P.H.; Bruce Rogers, B.S.; Eva Kline-Rogers, R.N., M.S.; and Kim A. Eagle, M.D. Author disclosures are on the abstract.

Project Healthy Schools is supported by unrestricted grants from the University of Michigan Health System, the Thompson Foundation, the Hewlett Foundation, the Mardigian Foundation and the Robert C. Atkins Foundation.

Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position.  The association makes no representation or warranty as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events.  The association has strict policies to prevent these relationships from influencing the science content.  Revenues from pharmaceutical and device corporations are available at www.heart.org/corporatefunding.