A tiny device used to repair the mitral valve, called the MitraClip, has sharply reduced death rates in patients with severe heart failure, in a large clinical trial.
The New York Times reports that almost 2m Americans have severe heart failure, and for them even mundane tasks can be extraordinarily difficult. With blood flow impeded throughout their bodies, patients may become breathless simply walking across a room or up stairs. Some must sleep sitting up to avoid gasping for air.
Drugs may help to control the symptoms, but the disease takes a relentless course, and most people with severe heart failure do not have long to live. Until now, there has been little doctors can do.
But researchers now report that a tiny clip inserted into the heart sharply reduced death rates in patients with severe heart failure. The report says in a large clinical trial, doctors found that these patients also avoided additional hospitalisations and described a drastically improved quality of life with fewer symptoms.
The results, reported at a medical meeting in San Diego, were far more encouraging than heart specialists had expected. “It’s a huge advance,” said Dr Howard Herrmann, the director of interventional cardiology at the University of Pennsylvania, which enrolled a few patients in the study. “It shows we can treat and improve the outcomes of a disease in a way we never thought we could.”
If the device is approved by the US Food and Drug Administration (FDA) for treatment of severe heart failure, as expected, then insurers, including Medicare, most likely will cover it.
In heart failure, the organ itself is damaged and flaccid, often as a consequence of a heart attack. The muscle pumps inefficiently, and in an attempt to compensate, the heart enlarges and becomes misshapen.
The enlarged organ tugs apart the mitral valve, which controls blood flow from the left atrium into the left ventricle. The distorted valve functions poorly, its flaps swinging apart. Blood that is supposed to be pumped into the body backs up into the heart and lungs. The report says a vicious cycle ensues: The heart enlarges, so the mitral valve leaks. The leaky mitral valve makes the heart enlarge even more, as it tries to compensate, and heart failure worsens.
In the new study, a device called the MitraClip was used to repair the mitral valve by clipping its two flaps together in the middle. (The clip is made by Abbott, which funded the study; outside experts reviewed the trial data.) The result was to convert a valve that barely functioned into one able to regulate blood flow in and out of the heart.
The report says until today, researchers were not sure that fixing the mitral valve would do much to help these patients. A smaller study in France with similar patients failed to find a benefit for the MitraClip. But that research included many patients with less severe valve problems, the procedure was not performed as adeptly, and the patients’ medications were not as well optimised as in the new study.
The report says in the new trial, 614 patients with severe heart failure in the US and Canada were randomly assigned to receive a MitraClip along with standard medical treatment or to continue with standard care alone. Among those who received only medical treatment, 151 were hospitalised for heart failure in the ensuing two years – 61 died. In contrast, just 92 who got the device were hospitalised for heart failure during the period, and 28 died.
The report says the results have left leading researchers unexpectedly optimistic. The trial sends “a very, very powerful message,” said Dr Gilbert Tang, a heart surgeon at Mount Sinai Medical Centre, which enrolled a patient in the trial.
“This is a game changer. This is massive,” said Dr Mathew Williams, director of the heart valve programme at NYU Langone Health, which had a few patients in the study.
Estimates of how many heart failure patients in the US are like those in the trial range from 1.6m to 2.5m, Williams said. But, he adds, the number who might ultimately be treated will be less than the number who could be treated.
The device itself costs about $30,000, not counting the cost of the hospital and doctors: a surgeon, an interventional cardiologist and an echo-cardiologist, among others, all in the operating room.
Cardiologists said in the report that the study was impeccably executed. The doctors inserting the device first had to demonstrate their expertise doing so. An independent group of experts ascertained that patients’ medical care was optimal; all too often, heart failure patients do not receive ideal treatment.
Patients with severe heart failure often are gravely ill, too sick to have open-heart surgery to have mitral valves replaced. “It’s not worth the risk,” said Dr Gregg Stone of Columbia University Medical Centre and New York-Presbyterian Hospital, the study’s principal investigator. (Stone reported no relevant conflicts, but said that Columbia University gets royalties from the sale of the MitraClip.)
But the new procedure is much less invasive than open-heart surgery. A cardiologist threads the device to the heart through a blood vessel in the groin. Once it reaches the heart, the MitraClip is guided to the valve, and the device is used to clip the two flaps together.
Not every cardiologist is equipped to insert the clip. “These are difficult procedures that require training and dedication,” Herrmann said. During the procedure, for example, a tiny echocardiogram camera is placed into the patient’s oesophagus behind the heart to show where the catheter with the clip is going.
Doctors must watch an X-ray screen and an echocardiogram as they guide the clip to the mitral valve. When the clip arrives, “you have to see where you are grasping to get a good result,” Tang said.
The report says the device is already approved by the FDA for patients too frail for surgery, but whose hearts are fine except for a mitral valve that does not function properly. Cardiologists predicted the FDA would quickly approve the device for patients with severe heart failure, as well. It already is used in Europe for these patients, but there had been no rigorous studies showing it helped.
The report says the new trial promises to alter prospects for many people with severe heart failure who had relatively few options. “This will change how we treat these patients,” Williams said. It’s possible, he added, that many would fare even better with the valve repair procedure if they were not so frail when they got it. “Maybe we need to start intervening earlier,” he said.
Background: Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes.
Methods: At 78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). The primary effectiveness end point was all hospitalizations for heart failure within 24 months of follow-up. The primary safety end point was freedom from device-related complications at 12 months; the rate for this end point was compared with a prespecified objective performance goal of 88.0%.
Results: Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.40 to 0.70; P<0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P<0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001).
Conclusions: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold.
Gregg W Stone, JoAnn Lindenfeld, William T Abraham, Saibal Kar, D Scott Lim, Jacob M Mishell, Brian Whisenant, Paul A Grayburn, Michael Rinaldi, Samir R Kapadia, Vivek Rajagopal, Ian J Sarembock, Andreas Brieke, Steven O Marx, David J Cohen, Neil J Weissman, Michael J Mack