Over six million Americans are living with heart failure and about half of them will die within five years of being diagnosed.Heart failure causes changes to the heart's structure and, as a result, some patients develop problems with the function of their valves, specifically the mitral valve. When the heart muscle is weakened, as is the case with most heart failure patients, the structure supporting the mitral valve becomes dilated. This prevents the valve from closing properly, resulting in mitral regurgitation (MR) where blood leaks backward through the mitral valve each time the heart contracts. When MR is caused by a secondary factor such as changes in the valve structure, it is called secondary MR. Primary MR is caused by a defect of the valve leaflets themselves.
Patients who experience MR against a background of existing heart failure are extremely ill because one condition exacerbates the other. The heart's weak and inefficient squeezing action cannot adequately circulate blood and can lead to multi-system organ failure. Both primary and secondary MR can also have potentially life-threatening, direct cardiac effects including atrial fibrillation and pulmonary hypertension. Unfortunately, recent studies find that the incidence of secondary MR is increasing in the developed world.
While patients with heart failure who develop secondary MR can be treated with medication, they have few options if medical therapy fails. Suzanne Richardson, MSN, RN, Clinical Program Manager for the Structural Heart and Valve Center at the Medical University of South Carolina (MUSC) explains, "In years past, if the patient was too high risk for surgery there was no other option and they entered a downward spiral leading to multi-organ dysfunction. Their quality of life declined and they tended to have more frequent hospitalizations for acute heart failure exacerbations. If they were not a candidate for advanced heart failure therapy such as transplant or LVAD, they could face a long slow decline." This underscores the importance of the recent FDA approval of the MitraClip®for percutaneous therapy in heart failure patients with secondary MR. "It's an option for people who had no option before," says Richardson.
The MUSC Structural Heart and Valve Center has participated in clinical trials of the MitraClip®since 2009. A previous trial (EVEREST II) led to a 2013 FDA approval for patients with primary MR. The next step was to prove the MitraClip®procedure was safe and effective for patients with secondary mitral regurgitation. "This study (COAPT) enrolled folks with heart failure who had maxed out on their medical options, but were too high risk for surgical mitral repair or replacement. The outcomes were very impressive! It really did help those patients," says Richardson.
Results from the COAPT study showed that patients who received the MitraClip®procedure had significantly lower hospitalizations for heart failure within two years compared to those who received standard care (35.8% vs. 67.9%; p<0.001).In addition, all cause mortality within two years of the procedure was also significantly lower in the MitraClip®group (29.1% vs 46.1% (p<0.001). Finally, the study found that 96.6% of patients who received the MitraClip®were free of device-related complications in the first year after the procedure.
MUSC was one of 100 centers recruiting patients for COAPT and enrollment topped out at 614 patients – not a very large recruitment goal for a national trial. However, the process of conducting the study was a slow endeavor and took more time to complete than other trials. "It was extremely hard to get patients enrolled. We needed to find high surgical risk patients with heart failure who still had significant MR after trying all the medical options and there's extensive medical therapy available to reduce regurgitation. We would spend months making adjustments to optimize patients' medications before we could even look at whether they might be a candidate for the trial," explains Richardson.
Transcatheter valve therapies have revolutionized the landscape of treatment options for patients with valvular heart disease. "It took us a long time to get to a transcatheter option for secondary MR. The mitral apparatus is an anatomical puzzle that's influenced by a multitude of factors," says Richardson. The COAPT trial was designed to eliminate as many of those factors as possible by requiring patients achieve guideline directed medical therapy before they could be considered for the transcatheter repair. "This meant heart failure specialists, interventional cardiologists, and cardiac surgeons worked closely together to optimize each patient’s care," Richardson explains. "Not only did we need a good percutaneous device, but we needed physicians with mitral valve experience who could implant it. Fifteen years ago there were no percutaneous valve options and our interventional cardiologists had never worked on valve structures. Now we have experienced implant teams where cardiac surgeons partner with interventional cardiologists to provide the full spectrum of available therapies.”
The COAPT study marked an important leap forward in treating these very sick patients. It confirmed the safety and efficacy of a transcatheter valve repair that is shown to reduce morbidity, decrease mortality, and improve quality of life. "This is just the beginning," says Richardson, "It might have taken us a while to get across the starting line, but the next five years will see huge progress in transcathether valve interventions. The number of therapies and the types of patients we can treat without surgery or in conjunction with surgery is just going to keep growing."
Mozzafarian D, Benjamin EJ, Go AS, et al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133:e38-e360.
Lung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on valvular heart disease. Eur Heart J. 2003;24:1231-1243.
Stone GW, Lindenfeld J, et al. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med 2018; 379:2307-2318.