Catheter ablation reduced the number of shocks delivered to patients who have defibrillators implanted after heart attacks, concluded a study published in late last month in the New England Journal of Medicine. While implantable cardioverter defibrillators (ICDs) are a mainstay of therapy to prevent sudden death for people who have a ventricular tachyarrhythmic event, the shocks are painful, can cause clinical depression, and do not offer complete protection against death from arrhythmia, according to the study authors.

“Since no device is likely to be fully protective against ventricular tachycardia or fibrillation, it would be clinically valuable to adopt an approach that reduced the absolute incidence of ventricular tachycardia or fibrillation so that the ICD served solely as a backup device,” the authors wrote in the report.

Mark Josephson, MD, chief of cardiology at Beth Israel Deaconess Medical Center (Boston) and professor of medicine at Harvard Medical School (Boston), led the Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia (SMASH-VT) study. SMASH-VT included 128 people who had defibrillators implanted after heart attacks. Half of them underwent ablation, half did not.

In an average follow-up period of 22.5 months, just eight of those who had ablation experienced defibrillator shocks, compared to 21 – a full third – of the group that did not have ablation.

Ablation was performed with the use of a substrate-based approach in which the myocardial scar is mapped and ablated while the heart remains predominantly in sinus rhythm. The primary end point was survival free from any appropriate ICD therapy.

The authors said that as compared with the control population, patients in the ablation group had a 65% reduction in the risk of receiving ICD therapy during the following two years. When anti-tachycardia pacing therapy was excluded from this analysis, there remained a 73% reduction in the risk of receiving subsequent ICD shocks.

“This effect may be clinically important, not only because of the reduction in the unpleasant experience of device discharge, but also in terms of subsequent adverse cardiovascular events,” the authors wrote.

There also was a reduction in deaths among those in the ablation group, the authors said. Eleven of those who did not have ablation died; there were just six deaths in the ablation group. The numbers were too small to reach statistical significance.

MIT research points to engineering of new blood vessels

Scientists at the Massachusetts Institute of Technology (Boston) say they have found a way to induce cells to form parallel tube-like structures that could one day serve as tiny engineered blood vessels.

The researchers found that they can control the cells’ development by growing them on a surface with nano-scale patterning. A paper on the work was posted this in an online issue of Advanced Materials.

Engineered blood vessels could one day be transplanted into tissues such as the kidneys, liver, heart or any other organs that require large amounts of vascular tissue, which moves nutrients, gases and waste to and from cells.

“We are very excited about this work,” said Robert Langer, an MIT professor and an author of the paper. “It provides a new way to create nano-based systems with what we hope will provide a novel way to someday engineer tissues in the human body.”

The work focuses on vascular tissue, which includes capillaries, the tiniest blood vessels, and is an important part of the circulatory system. The team has created a surface that can serve as a template to grow capillary tubes aligned in a specific direction.

The researchers built their template using microfabrication machinery at Draper Laboratory (Cambridge). Normally such technology is used to build micro-scale devices, but the researchers adapted it to create nano-scale patterns on a silicone elastomer substrate. The surface is patterned with ridges and grooves that guide the cells’ growth.

“The cells can sense [the patterns], and they end up elongated in the direction of those grooves,” said Christopher Bettinger, MIT graduate student in materials science and engineering and lead author of the paper.

The cells, known as endothelial progenitor cells (EPCs), not only elongate in the direction of the grooves, but also align themselves along the grooves. That results in a multicellular structure with defined edges, also called a band structure.

Once the band structures form, the researchers apply a commonly used gel that induces cells to form three-dimensional tubes. Unlike cells grown on a flat surface, which form a network of capillary tubes extending in random directions, cells grown on the nano-patterned surface form capillaries aligned in the direction chosen by the researchers.

The researchers said that they believe the technique works best with EPCs because they are relatively immature cells. Earlier attempts with other types of cells, including mature epithelial cells, did not produce band structures.

Growing tissue on a patterned surface allows researchers a much greater degree of control over the results than the classic tissue engineering technique of mixing cell types with different growth factors and hoping that a useful type of tissue is produced, said Bettinger.

“With this technique, we can take the guesswork out of it,” he said.

The next step is to implant capillary tubes grown in the lab into tissues of living animals and try to integrate them into the tissues.

Metabolic syndrome also found as risk for stroke

Metabolic Syndrome has for some time now been recognized as a huge risk for heart disease.

But a recent paper published in the journal Stroke shows that the condition leaves sufferers also at risk of stroke, and the distribution of this condition is not even, with women and minorities apparently more likely to acquire MS.

(Metabolic Syndrome is defined differently by different organizations, but the definition by the American Heart Association [Dallas] includes waist circumference, trigylcerides, high-density lipoprotein, blood pressure, and fasting glucose reading data).

In the Jan. 1 article describes how a team of authors led by Bernadette Boden-Albala, director of research of the Neurologic Institute at New York Presbyterian Medical Center, states that while cardiovascular risks associated with the syndrome are fairly well known, “the risk of stroke ... is less well established, with few prospective studies including ischemic stroke as a rigorously defined outcome measure.”

The Northern Manhattan Study, the basis for the article, enrolled almost 3,300 subjects in northern Manhattan to follow them between 1993 and 2001. Using telephone screening to determine whether the patient had been diagnosed with a stroke, the study lost only four patients to follow-up, with a median follow-up time of 6.4 years. Roughly 44% of the enrollees had the condition (48% of women, 38% of men), and half of Latino enrollees were diagnosed with MS, compared to 39% of whites, 37% of blacks.

Participants reported 176 ischemic strokes, 157 myocardial infarctions and 282 vascular deaths. The hazard ratio (HR) for ischemic stroke for the enrollees with Metabolic Syndrome was 1.5.

Women with Metabolic Syndrome had an HR for ischemic stroke of 2.0 compared to men, and Latinos also had a ratio of 2.0; whites and blacks both exhibited HRs of 1.3.

The authors conclude that Metabolic Syndrome “constitutes a major public health burden as defined by its prevalence [and] risk,” and due to the increasing prevalence of obesity, “the impact of the metabolic syndrome is likely to increase.” Consequently, “greater emphasis needs to be placed on the early diagnosis and treatment of [these] patients at risk for vascular disease.”

Gene variants linked to lipid levels CAD risk

Lifestyle factors like smoking, diet and exercise obviously influence a person's blood fat, or lipid levels, and are important risk factors for coronary artery disease (CAD). Now, scientists are trying to better understand the genetic contribution to cardiovascular risk.

In an international collaboration supported primarily by the National Institutes of Health, researchers say they have discovered more than 25 genetic variants in 18 genes connected to cholesterol and lipid levels. Seven of the 18 genes previously had not been connected to these levels, while the 11 others confirm previous discoveries, the NIH noted.

In the investigation, published online and in the February print issue of Nature Genetics, the associated genes were found through studies of more than 20,000 individuals and more than 2 million genetic variants, spanning the entire genome. These variants potentially open the door to strategies for the treatment and prevention of CAD.

"Now that we know that some of these new genes can affect cholesterol levels, and can have an effect on CAD, we might be able to start looking for a new pharmaceutical to treat the disease," David Schlessinger, PhD, chief of the National Institute on Aging's Laboratory of Genetics, told Cardiovascular Devices & Drugs.

The purpose of the study was to identify comprehensively genetic variants that influence lipid levels and to examine the relationships between these genetic variants and risk of CAD. High levels of low-density lipoprotein (LDL) — "bad" cholesterol — appear to increase the risk of CAD by narrowing or blocking arteries that carry blood to the heart.

High levels of high-density lipoprotein (HDL) — "good" cholesterol — appear to lower the risk. High levels of triglycerides, which make up a large part of the body's fat and are also found in the bloodstream, are also associated with increased risk of CAD.

Cristen Willer, PhD, of the University of Michigan's School of Public Health (Ann Arbor), and Serena Sanna, PhD, of the C.N.R. Institute of Neurogenetics and Neuropharmacology (Monserrato, Italy), and other members of the SardiNIA Study of Aging, including investigators at NIA, conducted the study, along with members of the Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study, which included investigators in North Carolina, Michigan, Finland, Los Angeles and from the National Human Genome Research Institute. The study relied on a relatively new approach, known as a genome-wide association study (GWAS).

"It's a notable consortium effort, because one of the things that's become clear in these genome-wide association studies, is the more people you have involved with good results, the stronger the results become and the greater your power is to being able to detect the genes involved," said Schlessinger, the NIA project officer for SardiNIA.

The GWAS strategy enables researchers to survey the entire human genetic blueprint, or genome, not just the genetic variants in a few genes. The human genome contains about 3 billion base pairs, or letters, of DNA.

Small, single-letter variations naturally occur about once in every 1,000 letters of the DNA code. Most of these genetic variants have not yet been associated with particular traits or disease risks. However, in some instances, people with a certain trait, such as higher levels of LDL cholesterol, tend to have one version of the variant, while those with lower levels are more likely to have the other version. In such instances, researchers may infer that there is an association between the values of the trait and the variants in the gene.

Typically, GWAS studies have been carried out in samples where all individuals are examined with the same gene chip, an experimental device that allows investigators to measure more than 100,000 genetic variants in a single experiment. But in this study, investigators developed and employed new statistical methods that allowed them to combine data across different gene chips and examine much larger numbers of participants.

With the statistical power gained by new programs that facilitated pooling of the large SardiNIA, FUSION and Diabetes Genetic Initiative (DGI) datasets, researchers identified variations in 18 genes that influence HDL, LDL and/or triglyceride levels.

"These results are yet another example of how genome-wide association studies are opening exciting new avenues for biomedical research," said Francis Collins, MD, PhD, NHBRI Director, a co-author of the study and an investigator in NHGRI's Genome Technology Branch. "While some of the genetic variants we identified are known to play a well-established role in lipid metabolism, others have no obvious connection. Further studies to identify the precise genes and biological pathways involved could shed new light on lipid metabolism."

Scientists estimate that the genetic contribution to lipid levels is about 30% to 40%; the genetic variants uncovered in the new study are responsible for about 5% to 8% of that contribution, the researchers note. "In this study we carried out a comprehensive search for common variants of large effect. The genetic factors still to be discovered might turn out to be common variants with smaller effects or rare variants with a large effect," said Karen Mohlke, PhD, of the University of North Carolina (Chapel Hill), who co-directed the study with Gon alo Abecasis, PhD, of the University of Michigan's School of Public Health.

To determine if the genetic variants associated with lipid levels also influence risk of heart disease, the researchers compared their results with results from the recent genome-wide study of CAD Wellcome Trust Case Control Consortium (Oxford, UK) involving 15,000 British individuals. They found that all gene variants associated with increased LDL levels also were more prevalent among people with CAD. People with the gene variant for high triglyceride levels also had an increased risk for CAD, though the relationship was not as strong. No relationship was found between HDL and CAD.

Schlessinger told CD&D that this study was just a first step in a long path to potential clinical implications. "What we're looking for, ultimately, are novel therapeutics and/or life-style modifications that can b recommended to individuals to help manage blood lipid levels and reduce risk of heart disease."

Warnings are sought for DTC advertisements for implants

Consumers Union (CU; Washington) last month filed a petition with the FDA requesting that the agency require that all consumer advertisements for implantable devices — such as heart stents, heart valve replacements, knee, hip and cosmetic implants — carry a warning about the possibility of dangerous infections or failures of the devices once they are in the body.

The petition asks that these advertisements provide two types of information: “the very real danger of healthcare-acquired infections that can and do result from surgery and follow-up care; and the expected life span of the device before failure occurs. It says that both circumstances – the risk of infections and a device outliving its life span “can and do cause death or serious morbidity and expense.

Implantable device makers recently have launched a wave of direct-to-consumer (DTC) advertisements for their products, and Consumers Union said a review of these ads shows that most lack basic information about the possibility of severe or fatal side effects.

“There is no question that many of these devices can restore high quality of life in patients, but we are concerned that serious and possibly deadly side effects like infections are consistently understated in these device ads,” said Bill Vaughan, senior policy analyst for Consumers Union, publisher of Consumer Reports. “We’re asking the FDA to require clear warnings about the dangers of infection during and following such surgery, and information about how long the devices are likely to last once they are in the body,” Vaughan said.

The petition says that some healthcare facilities “do a better job than others in preventing infections and some make this information available to the public as a result of State laws or voluntary disclosure.” Thus it says that all implanted devices carry a warning statement, and it provides such a statement as an example:

“The surgery and care involved in the placement of this device may result in an infection, or other adverse events, that can lead to death or injury. Be sure to ask your doctor and hospital about infection rates at the facility where the surgery will be performed. In addition, ask your doctor about the long-term failure rates so that you are aware of when the implant is likely to need to be replaced.”

The petition goes on to say that it has reviewed device advertisements, it charges that adverse effects “including death — are consistently understated” in the ads, and it encourages the FDA to review these ads. But it says the specific purpose of the petition is to recommend to the FDA it “review the quality of all device ads” and that consumers “be advised to seek out facilities with the strongest anti-infection programs and devices with long-term data about failure rates.”

The petition assures that it is not trying to discourage people from seeking out device therapies. But then adds: “we do believe that unintended side effects ... can be minimized if the public is better educated to avoid facilities which are not practicing the highest level of anti-infection practices.

That article says the Agency for Healthcare Research and Quality (Washington) reports that the “complication of device, implant or graft” was the third most common of the principal diagnoses for hospital stays with MRSA infection in 2004.

It says that this study reviewed more than 300,000 hip procedures and that the in-hospital mortality rates associated with these three procedures were 0.33%, 3.04%, and 0.84%, respectively; perioperative complication rates associated with the procedures were 0.68%, 1.36%, and 1.08% respectively; for deep vein thrombosis or pulmonary embolism, 0.28%, 1.88%, and 1.27% for decubitus ulcer; and 0.05%, 0.06%, and 0.25% for postoperative infection. Rates of readmission for any cause within 90 days ran between 9% for total replacement to 21% for partial.

“Other Department of Health and Human Services agencies recognize the importance of fighting HAIs and empowering consumers to understand the dangers of infection and the efforts individual facilities are taking to fight infection,” CU said.

Experienced units give better heart defect neonatal care

A team of researchers at the University of Michigan (U-M; Ann Arbor) suggests that there may be a way to give babies born with severe heart defects a better chance at living.

The study results indicate it’s important to get such infants to the hospitals that are the most experienced at handling such cases.

The researchers found that infants with specific complex heart defects are much less likely to die before leaving the hospital if they are treated at the centers that treat the largest numbers of these patients. This relationship between hospital volume and mortality has been seen in adult heart operations, but the new study suggests it holds true for infants as well.

The study is published online in the journal Pediatric Cardiology.

“A generation ago, we were just happy when these patients lived, but that’s not good enough any more,” said lead author Jennifer Hirsch, MD, a U-M pediatric cardiac surgeon and member of the Michigan Congenital Heart Center.

Hirsch and her colleagues based their study on data from the 2003 Kids’ Inpatient Database, a national database sponsored by the Agency for Healthcare Research and Quality (AHRQ; Washington) that includes information on children hospitalized in 36 states.