Stem Cells Show Promise as Heart Failure Treatment

HealthDay – 1 hr 40 mins ago MONDAY, July 23 (HealthDay News) -- Scientists who used modified stem cells to rejuvenate damaged and aged heart cells from elderly heart failure patients say their research could one day lead to new treatments for the illness.

"Since patients with heart failure are normally elderly, their cardiac stem cells aren't very healthy," Sadia Mohsin, one of the study authors and a postdoctoral research scholar at San Diego State University's Heart Institute, explained in a news release from the American Heart Association (AHA). "We modified these biopsied stem cells and made them healthier. It is like turning back the clock so these cells can thrive again."

The study was to be presented Monday at an AHA meeting, in New Orleans, and published simultaneously in the Journal of the American College of Cardiology.

The stem cells taken from the patients were modified with a protein called PIM-1, which promotes cells survival and growth. The modified stem cells helped the signaling and structure of the patients' heart cells by boosting the activity of an enzyme called telomerase, which elongates telomeres.

Telomeres are the caps on the ends of chromosomes that are involved in cell replication. Aging and disease occur when telomeres break off.

"There is no doubt that stem cells can be used to counter the aging process of cardiac cells caused by telomere degradation," Mohsin said.

While the study did use human heart cells, it was conducted in the laboratory and remains in its early stages. However, tests conducted in mice and pigs also found that telomere lengthening resulted in new heart tissue growth in just four weeks.

"Modifying aged human cardiac cells from elderly patients adds to the cell's ability to regenerate damaged heart muscle, making stem cell engineering a viable option," Mohsin said. "This is an especially exciting finding for heart failure patients. Right now we can only offer medication, heart transplantation or stem cell therapies with modest regenerative potential, but PIM-1 modification offers a significant advance for clinical treatment."

One expert called the research "exciting."

The stem cell technique "is enabling endogenous

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Obesity, larger waist size associated with better outcomes in heart failure patients

ScienceDaily (July 3, 2012) — A slim waist and normal weight are usually associated with better health outcomes, but that's not always the case with heart failure patients, according to a new UCLA study.

See Also:Health & MedicineObesityHeart DiseaseCholesterolStroke PreventionDiseases and ConditionsDiet and Weight LossReferenceArtificial heartIschaemic heart diseaseRheumatic feverHypertension

Researchers found that in both men and women with advanced heart failure, obesity -- as indicated by a high body mass index (BMI) -- and a higher waist circumference were factors that put them at significantly less risk for adverse outcomes.

The study findings are published in the July 1 online issue of the American Journal of Cardiology.

Heart failure affects 5.8 million people, including 2.5 million women. Approximately one-half to two-thirds of heart failure patients are overweight or obese.

Women and men are known to have differences in body composition and body-fat distribution, and this study is one of the first to specifically assess the impact of BMI and waist circumference on women and compare it with men.

The findings also offer further insight into an observed phenomenon in chronic heart failure known as the "obesity paradox": Obesity is a known risk factor for developing heart disease and heart failure, but once heart failure has manifested, being overweight may provide some protective benefits.

"The study provides us with more insight about how both genders of heart failure patients may be impacted by the obesity paradox," said senior author Dr. Tamara Horwich, an assistant professor of cardiology at the David Geffen School of Medicine at UCLA. "Heart failure may prove to be one of the few health conditions where extra weight may prove to be protective."

For the study, researchers analyzed data on advanced heart failure patients treated at UCLA Medical Center from 1983 to 2011. The team assessed 2,718 patients who had their BMI measured at the beginning of heart failure treatment and 469 patients who had their waist circumference measured at the beginning of treatment.

Using standardized measures, the researchers identified men or women as having a high BMI if they were greater or equal to 25 kg/m² -- this included both overweight patients (25 to 29.9 kg/m²) and obese patients (30 kg/m² or greater).

For men, a high waist circumference was considered 40 inches (102 cm) or greater, and for women, 37 inches (88 cm) or greater. This assessment also included patients who were either overweight or obese.

At the two-year follow-up, researchers used statistical analysis and found that in men, a high waist circumference and high BMI were associated with event-free survival from adverse outcomes like death, the need for a heart transplant, or the need for ventricular assist device placement.

Women with a higher BMI also had better outcomes than their normal-weight counterparts, and women with a high waist circumference also trended toward improved outcomes.

Both men and women with a normal BMI and waist circumference were at a substantially higher risk for these adverse outcomes. In fact, a normal BMI was associated with significantly worse outcomes -- a 34 percent higher risk in men and a 38 percent higher risk in women -- than a high BMI.

Normal waist circumference was also associated with an increased risk of adverse outcomes in both genders, with men's risk doubling and women's risk tripling.

"We knew that obesity might provide a protective benefit for heart failure patients, but we didn't know whether this obesity paradox applied specifically to women with heart failure, as well as men -- and it does," Horwich said.

BMI measurement has been used for years as a surrogate measure of body fat. Since it measures all mass -- including lean muscle, which weighs more than fat -- the measurement may not be specific for total body fat. Waist circumference is a newer addition that may provide a more direct connection to body fat, since it measures the fat accumulated around the belly.

"The study also demonstrates how BMI and waist circumference can be used together to provide a more accurate measure of fat in the body to help determine obesity and assess risk," said the study's first author, Adrienne L. Clark, a resident in the department of medicine at the Geffen School of Medicine.

According to Horwich, no one knows exactly why the obesity paradox exists for heart failure patients, but there are several possible explanations.

Being underweight is traditionally associated with a poorer prognosis in heart failure patients. Obesity may be at the other end of the spectrum, and patients may thereby benefit from increased muscle mass, as well as metabolic reserves in the form of fatty tissue. In addition, increased levels of serum lipoproteins that are associated with increased body fat may play an anti-inflammatory role, neutralizing circulating toxins and inflammation-related proteins.

Obese patients also present at an earlier stage of heart failure due to increased symptoms and functional impairment caused by excess body weight, so they may be getting help sooner, which also could improve outcomes, the researchers said.

The next steps in research will include larger studies with longer follow-up times, as well as a closer look at the physiology behind the obesity paradox.

The study was funded by the National Heart, Lung and Blood Institute, part of the National Institutes of Health (grant 1K23HL085097).

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Taking fitness plateaus from failure to feedback

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Herbal Remedy Ingredient Tied to Cancer, Kidney Failure

HealthDay – 43 mins ago THURSDAY, April 12 (HealthDay News) -- A toxic component of a plant used in certain types of herbal remedies can cause kidney failure and upper urinary tract cancer, researchers warn.

Aristolochic acid is found in Aristolochia herbal remedies, which have been used for centuries and still are used in many countries.

This study of 151 patients with upper urinary tract cancer in Taiwan concluded that aristolochic acid is a primary contributor to the incidence of this cancer in Taiwan, where the incidence is the highest reported anywhere in the world and where Aristolochia herbal remedies are widely used.

The researchers found that 83 percent of the patients had evidence in their kidneys of DNA changes that are related to the plant toxin and associated with the development of cancer.

"We believe our latest research highlights the importance of a long-overlooked disease that affects many individuals in Taiwan, and, by extension, in China and other countries worldwide, where Aristolochia herbal remedies traditionally have been used for medicinal purposes," Dr. Arthur Grollman, a professor of pharmacological sciences at Stony Brook University School of Medicine, in New York, said in a university news release.

In previous research, Grollman and his colleagues linked the ingestion of Aristolochia clematitis (commonly known as birthwort) to widespread kidney disease in the Balkans.

The findings of the studies show that public health officials need to take action to stop kidney damage and upper urinary tract cancer related to aristolochic acid, Grollman said.

The study was published online April 9 in the journal Proceedings of the National Academy of Sciences.

More information

The U.S. National Kidney Disease Education Program explains how to keep your kidneys healthy.

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Stem-Cell Trial Failed to Treat Heart Failure

HealthDay – 15 hrs ago SATURDAY, March 24 (HealthDay News) -- An innovative approach using patients' own bone marrow cells to treat chronic heart failure came up short in terms of effectiveness, researchers report.

Use of stem cell therapy to repair the slow, steady damage done to heart muscle and improve heart function is safe, but has not been shown to improve most measures of heart function, the study authors said.

"For the measures we paid most attention to, we saw no effect, there is no question about that," said researcher Dr. Lemuel Moye, a professor of biostatistics at the University of Texas School of Public Health in Houston.

"Ultimately, this is going to pay off handsomely for individuals and for public health in general, but it's going to take years of work," Moye said. "We are the vanguard looking for new promising lines of research."

While the hoped-for results didn't materialize, there appeared to be a small improvement in some patients, he said. "When we looked at another commonly used measure of heart function called ejection fraction, or the strength of the heart's pumping, that's where all the action was," Moye noted.

It's hard to know which measures of heart function to look at, Moye explained. "We have had some difficulty with that," he said.

Future research will look at other measures of heart function, pay more attention to the characteristics of the cells that are injected and determine which cells are best, he added.

Cardiac cells and other types of specially prepared cells are available now that were not accessible when this study started in 2009, Moye pointed out.

The results of the trial, which was sponsored by the U.S. National Heart, Lung, and Blood Institute, were to be presented Saturday at the American College of Cardiology's annual meeting in Chicago. The report was also published online March 24 in the Journal of the American Medical Association.

For the study, Moye and colleagues worked with 92 patients, average age 63 and mostly male, who had heart failure with and without chest pain. They were randomly assigned to receive either an injection of 100 million bone marrow cells from their own bone marrow, or an inactive placebo. Patients in both groups also received aggressive medical therapy.

During the trial, the researchers looked for improvements in blood volume in the heart, oxygen use by the heart and blood flow through the heart.

After six months, the researchers said they saw no difference between the groups in these measures. Nor was any difference seen in the extent of heart damage, heart movement during contractions or overall condition.

Moye's team did find a slight improvement in the heart's ability to pump blood among patients 62 and younger. The improvement was small, only 3.1 percent, but patients in the placebo group declined 1.6 percent in this measure, they said.

It's possible that cells of younger people are more potent, and that's borne out by improvement in heart function seen in younger patients who did not get bone marrow cells, Moye said.

"We have demonstrated that the characteristics of the cells are correlated with heart function, so that the better the cells, the better the response -- so even in patients who did not get stem cells, those younger patients did better," he said.

Commenting on the study, Dr. Gregg Fonarow, director of the Ahmanson-University of California, Los Angeles, Cardiomyopathy Center, said there has been "tremendous interest in cell-based therapies" to treat acute and chronic heart disease and chronic heart failure.

Most studies trying delivery of different types of cells have been small and not adequately powered to demonstrate improvement in cardiac function or clinical outcomes, and results have been mixed, Fonarow said.

"While this study failed to meet any of its primary or secondary endpoints, the insights provided will be helpful in designing future trials," Fonarow added. "However, whether cell-based therapies will be of therapeutic value to patients with heart disease and heart failure remains to be seen."

More information

For more information on heart disease, visit the American Heart Association.

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