David Cox 

Change of heart: can we do better for heart patients than a transplant?

Fifty years after the first heart transplant, the operation remains very expensive with mixed outcomes. A new approach focuses on repair instead of replace
  
  

The survival rate 12 years after heart transplant surgery is still just 50%.
The survival rate 12 years after heart transplant surgery is still just 50%. Photograph: Alamy Stock Photo

In the early hours of 3 December 1967, Prof Christiaan Barnard gazed down into the void and felt a chill ripple through his veins as he considered the historic nature of what he was about to attempt. The gaping chasm lying before him was the empty chest cavity of a 54-year-old former boxer called Louis Washkansky. Barnard had just removed Washkansky’s heart, a bloated organ left ravaged and scarred by repeated coronary attacks, and now he had just minutes to try to save his life by inserting a heart taken from Denise Darvall, a 25-year-old woman left brain dead after being struck by a car that day.

At the time, cardiac transplant surgery was barely a decade old, pioneered by a handful of individuals who had developed a radical method of switching a heart from one body to another – but all previous transplants had been done in dogs. As they worked to stitch the new organ into Washkansky’s body and then shock it into life, Barnard and his team were improvising, guided only by a few dozen animal studies, the suggestions of scientific papers and their own instinct. But at 6.13am, after almost four hours of surgery, Washkansky’s transplanted heart started to stir. As Barnard would write: “Little by little it began to roll with the lovely rhythm of life.”

It would prove to be a defining moment in the history of medical science. While Washkansky himself would die of pneumonia just 18 days later, his body weakened by intensive antirejection treatment, his case paved the way for hundreds of heart transplants in the following years. Now, 50 years on from Barnard’s achievement, 4,000 heart transplants are performed around the world each year. But while some patients live for decades, complications persist due to the need for constant immunosuppressant treatment, meaning the survival rate after 12 years is still just 50%. In addition, while studies in the US have found that more than 20,000 Americans could benefit from a heart transplant each year, just 2,000 transplants are performed there due to a shortage of donors.

But many scientists believe we are on the verge of a new medical revolution. Advances in regenerative medicine will allow us to repair damaged hearts instead of replacing them. In all mammals, it’s almost impossible for a damaged heart to repair itself. Within minutes of being deprived of oxygen due to a blocked artery, the heart’s muscle cells start to die. If surgeons are able to tackle the blockage within one hour, the damage can be reversed. If 12 hours have passed, up to 1bn heart cells may already be lost, replaced only by tough, rigid scar tissue.

“The problem is that the regenerative power of the heart is lower than other organs,” says Dr Tim Henry, director of cardiology at the Cedars-Sinai Medical Center in Los Angeles. “If you lose half your liver, it will grow back. Your skin heals completely very quickly. But for people whose heart failure isn’t treated in time, or who have already had one heart attack, there’s permanent, significant damage which leaves them requiring a transplant.”

Over the past 15 years, scientists have experimented with taking stem cells from the blood or bone marrow and injecting them into badly damaged hearts. This typically works well in improving blood flow to the heart, helping patients who have bad blockages in their arteries. But despite numerous attempts, these individual stem cells have been unable to grow back much of the lost heart muscle. The body’s immune responses are so hostile to new cells implanted into the heart that even when the patient’s own tissue is used, 90% of the cells still die.

“The stem cell approach has shown some benefit, but it’s been relatively short-lived,” says Prof Richard Farndale of the University of Cambridge. “What generally happens is that the stem cells fail to attach to the heart and are lost into the bloodstream fairly quickly.”

However, a new approach appears to hold a lot more promise. Scientists are growing “heart patches”, tiny beating pieces of heart muscle, in small dishes in the lab. They are made by taking a drop of blood from a patient and engineering the blood cells into a layer of fully formed cardiac tissue. This is genetically matched to that person, and can be engrafted into the heart to replace damaged areas. This has been tested in mice and will soon be tested in pigs. In the next five years, scientists hope to launch a clinical trial to apply the patches in humans. At a cost of about £70,000 a patient, it promises to be a far more economically viable alternative to heart transplants, which, with the huge surgical teams required, cost the NHS up to £500,000.

“The hope is that by providing a patch of tissue which already beats and contracts, instead of just individual cells, the body’s built-in programming will take over and assimilate it into the heart as if it was already there,” says Tim Kamp, professor of regenerative biology, who builds heart patches at the University of Wisconsin.

One of the challenges in coming years is to ensure that the new patch electrically integrates with the heart so that both beat in synchrony. Scientists hope that because the patch will be so similar to the existing heart muscle, natural bodily processes will take over.

“We anticipate this will happen, but we have to make sure and be really cautious,” Kamp says. “The heart isn’t a USB socket which we can just plug things into. For patients with severe heart failure, the whole heart dilates to try to adapt to the damage. It changes shape from being like a football to a big basketball. But we hope these patches will be able to heal a much larger area of damage than single cell injections. And if multiple patches are required to replace multiple areas of scarring, we can put those in. This technology may really provide a whole avenue of hope for people with these conditions who badly need new treatments.”

 

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