Showing posts with label heart failure. Show all posts
Showing posts with label heart failure. Show all posts

Tuesday, November 26, 2013

Damaged hearts may be healed by their own stem cells

Thanks to stem cells, each of us develops from a single-celled embryo into a fetus with hundreds of different cell types. Stem cells multiply and specialize until they become heart muscle, bone, nerves, etc. Tissues like skin keep pools of stem cells on hand into adulthood, activating them as needed to replace worn out cells in a constant turnover.

But not the heart. Cardiologists believed for a long time that you get one set of heart cells for life. If you lost a bunch in the wake of heart attack, you had to live with whatever was left. In recent years, however, researches have revised that view. There is cell turnover in the heart, albeit as a much slower pace than that seen in other tissues.

The existence of such replenishing mechanisms suggested that it may be possible to coax them into action to regenerate heart muscle damaged by disease. Results of early human trials have been positive, although there is still work to do before such treatments become part of clinical practice.

It may be no surprise then stem cell-based therapies were a focus of the recently held UAB Comprehensive Cardiovascular Center’s Annual Symposium. We sat down with Sumant Prabhu, M.D., director of the center and symposium organizer to talk about the promise of regenerative medicine.



1:32 Dr. Prabhu said he organized the symposium with this theme at this time because his team wanted to focus on the next wave of science and therapeutics in cardiology. He believes that stem cell-based, genetic and tissue regeneration therapies will dominate the field in the coming years, just as drugs and devices did in during eras past. The symposium was designed to foster new collaborations in these areas among leading researchers.

3:19 Several symposium presentations were dedicated to stem cells that are present in the heart, and on attempts to manipulate them such that the become needed replacement cells in damaged hearts. Over the last ten years, clinical trials have examined the value of stem cells taken from the bone marrow or blood to repair damaged hearts, but a more recent thrust is the use of stem cells in the heart itself.

4:37 Joshua Hare, M.D., from the University of Miami, described in his presentation the use of mesenchymal stem cells, which can become bone, cartilage or fat cells, and how they showed "incredible promise" in clinical trials.  The studies looked at whether they could repair heart tissue after heart attack, and heart failure, the loss of pumping efficiency, seen in the wake of heart attacks. While these studies are promising, the field still has a long way to go before stem cell treatments become part of standard medical practice.

5:35 Harvard's Piero Anversa, M.D., delivered the keynote lecture for the symposium on the topic of stem cells in the heart, their discovery, their use in animal studies to repair hearts damaged by heart attack. In particular he described strong, early results in the Phase I human Scipio trial. In this trial, researchers removed stem cells from the hearts of patients as they underwent coronary bypass surgery. The research team then reinfused each patient's stem cells into their hearts after the surgery, where they proved to be safe, to improve pumping function and to lessen the amount of dead tissue in the heart.

6:39 Stem cell therapies target tissue that forms scar when damaged by a heart attack. Scar tissue is made of structural cells instead of functional muscle cells, and scars interfere with the hearts ability to pump blood (heart failure). Dr. Prabhu said there are often pockets of live tissue within the scarred area.  The hope is that added stem cells will receive signals from the surviving areas that turn them into the kind of cells that either improve the remaining tissue or build new tissue.

9:04 It was actually the dawn the nuclear era that made possible the discovery of the slow stem-cell led turnover of heart muscle. Heart cells exposed to low level of radiation from power plants, for instance, could the be carbon dated to show cell turnover. There is not much turnover, but over a lifetime it makes hearts more durable. After a heart attack, the process of stem-cell based tissue replacement seems to kick up a notch, said Dr. Prabhu, but obviously not enough to counter the massive damage caused by a heart attack. What if researchers could temporarily pump up this natural response? Would more the presence of more stem cells mean more rebuilding of tissues in of damaged areas?

10:28 Whether injected stem cells themselves bring about cardiac repair or whether they trigger some chain reaction that brings about repair is a matter of debate. How much heart muscle for instance that grows back in damaged hearts after stem cells are infused has varied considerably from study to study. What has been shown in animal studies is that stem-cell driven regeneration can be manipulated to improve cardiac function. Human studies are seeking to confirm that now.


Monday, March 11, 2013

What others missed about heart failure

Every research medical center markets itself as interdisciplinary, with brochures proclaiming that University X is breaking down barriers between research specialties to solve medical mysteries.

Perhaps it started in 2002 when Elias A. Zerhouni, M.D., then newly appointed director of the National Institutes of Health (NIH), began crafting his "road map" for the agency. He concluded that the quickest way to deliver more breakthroughs would be to put multidisciplinary teams on the case, and with the institutions best suited to do so winning more grants. I could argue that UAB has done this better than most, but that's another story.

My point is that I have a high threshold for getting excited about the "interdisciplinary" aspect of anything. It has to be "real," and I think a study, led by UAB's Ali Ahmed, M.D., and making news today, fits the bill.

The study found that an old heart failure drug digoxin, used less and less since it “failed” its clinical trial 16 years ago, may do something no drug has achieved since: dramatically reduce the chances that heart failure patients check into the hospital within 30 days of first taking the drug.

Who cares you say?  The nation's hospitals and Medicare care a great deal. Medicare penalized thousands of hospitals millions of dollars last year for admitting too many heart failure patients too often. The agency leveled the penalties with the rationale that many admissions and readmissions are preventable if care is handled properly, and because frequent admissions cost the agency $17 billion each year. Digoxin is known is reduce scary symptoms of acute heart failure like shortness of breath that send people racing to emergency rooms.

The current study is a re-analysis of the 1997 DIG study in which digoxin failed to lower the risk of death (all-cause mortality) in patients with chronic heart failure. The treatment did reduce the risk for hospitalization, but that fact was largely overlooked. After it failed to reduce mortality, digoxin went from one of the most prescribed heart failure drugs to an afterthought. In the meantime, newer drug classes like beta blockers and aldosterone antagonists came into vogue after successfully reducing both mortality and long-term hospitalization in pivotal trials. And yet, they don't appear to fully address the acute symptoms driving readmissions.

The current analysis found that digoxin could reduce admission for heart failure within 30 days of first taking it by 34 percent. But what made Ahmed check on whether it could do this in the first place? Marketing effort aside, it looks like it was an interdisciplinary approach. Let's look at his titles.

Within the School of Medicine:
  • professor in the division of Gerontology, Geriatrics, & Palliative Care
  • profession in the division of Cardiovascular Disease
Within the School of Public Health 
  • professor in the Department of Epidemiology
  • director of the Advanced Illness, Multimorbidity and Heart Failure (AIM-HF) program in the UAB Center for Aging
Comparing problems faced by heart failure patients, understanding the mechanisms of drugs old and new,  and sifting through public health and policy trends, Dr. Ahmed and his team were able to frame a useful question, and answer it - potentially and in part, with a solution overlooked by the field.

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Here is some media coverage of the digoxin ACC presentation: