In less than a decade, transcatheter aortic valve replacement (TAVR) has developed into an established procedure for restoring valve function in inoperable patients and those at high surgical risk, with promising potential for use in less-sick populations. Similarly, a percutaneous technique for mitral valve repair has been approved for clinical use, and transcatheter mitral valve replacement is now being explored.
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In their most fundamental applications, these percutaneous approaches to valve therapy provide more options for treating inoperable patients with valve diseases. “Now that there are alternatives, we don’t have to give these patients bad news,” says cardiothoracic surgeon Lars G. Svensson, MD, PhD, Chair of Cleveland Clinic’s Miller Family Heart & Vascular Institute.
But the latest in the trend toward transcatheter valve therapies is their application to expanding populations and indications. Cleveland Clinic surgeons and cardiologists see a rosy future for these approaches — and they are helping shape that future on multiple fronts.
A decade of progress in TAVR
Work with TAVR at Cleveland Clinic dates back to early explorations of the technology in 2004 by Dr. Svensson and others. Cleveland Clinic became involved in TAVR trials in 2006, and its cardiologists and surgeons continue to evaluate various transcatheter approaches to aortic and mitral valve procedures.
“With every procedure we do, I’m left with a sense of excitement and appreciation of the technology,” says interventional cardiologist Amar Krishnaswamy, MD. He calls TAVR one of the most exciting developments in the history of interventional cardiology. “It has changed the paradigm for treating aortic stenosis — as well as whom we treat.”
Cleveland Clinic interventional cardiologists and cardiac surgeons collaborate on an average of eight TAVR cases per week. At 0.4 percent, Cleveland Clinic’s mortality rate is far below the national average of 4 to 6 percent. Interventional cardiologist Samir Kapadia, MD, attributes this success to a team approach. “It’s a necessity for good outcomes,” he says.
Today, Dr. Kapadia and his colleagues perform many TAVR cases without intubation or general anesthesia, using conscious sedation and pain medications. “Recovery is much easier,” he explains.
The expanding TAVR patient pool
TAVR was developed as an option for extreme-risk, inoperable patients. Five-year results of the PARTNER 1B trial, which compared TAVR with medical treatment in this population, were presented at this year’s annual scientific session of the American College of Cardiology (ACC) and simultaneously published in The Lancet. In this study, TAVR resulted in a 22 percent survival benefit and a 28 percent reduction in cardiovascular mortality compared with standard treatment.
“This was the first — and will probably be the only — randomized aortic stenosis trial that includes a standard treatment group, since its results make it unethical to treat severe aortic stenosis with medical therapy alone without aortic valve replacement,” says Dr. Kapadia, lead author of the PARTNER 1B report.
Its sister trial, PARTNER 1A, assessed TAVR in another population — patients with aortic stenosis at high surgical risk — and found TAVR to be equivalent to surgical aortic valve replacement in all parameters. Five-year results were also presented at ACC 2015 and published in The Lancet.
“The rigorous trial performance and comparative effectiveness analyses of adjudicated end points give us confidence that in high-risk surgical patients, there is no advantage to surgical valve replacement over TAVR as far as risk of death,” says Dr. Svensson, a key co-investigator in PARTNER 1A.
Cleveland Clinic has proceeded to using TAVR in patients at intermediate surgical risk through participation in the multicenter PARTNER 2A trial, which is randomizing such patients to surgery or TAVR. Results have not yet been published, but Dr. Krishnaswamy notes that European data on TAVR in this population have been encouraging.
Remaining challenges in TAVR
TAVR can be performed via a transfemoral, transapical, transaortic or subclavian approach, but as delivery catheters become smaller, more patients can be treated via the less invasive transfemoral route. “The ability to perform procedures in smaller arteries allows us to bring the technology to a larger group of patients with lower rates of stroke and vascular complications,” says Dr. Krishnaswamy.
Several issues with TAVR have yet to be resolved, including the need for post-procedure pacemakers in 5 to 25 percent of patients (depending on the type of valve used). But of all complications, paravalvular leak may be the most serious: The more severe the leak, the greater the risk of death and symptoms.
Cleveland Clinic is involved in clinical trials of three repositionable transcatheter valve devices designed to reduce paravalvular leaks, reduce the risk of vascular complications and provide access through a vessel as small as 5.5 mm. Interventional cardiologist E. Murat Tuzcu, MD, is national principal investigator (PI) of a trial testing the effectiveness of Direct Flow Medical’s recapturable and repositionable device for minimizing paravalvular leaks.
An additional safety issue is the risk of stroke with TAVR, which remains at 2.5 to 3 percent — higher than with surgical valve replacement. Yet placement of a filter in the carotid arteries at the time of TAVR may reduce stroke risk, a strategy embraced by developers of several investigational embolic protection systems.
Dr. Kapadia is national PI of a study using one such filter system, developed by Claret Medical. “This is an important step forward, because preventing strokes in this way may yield a lower stroke risk than with surgery,” he says.
Valve-in-valve TAVR promises more progress for riskiest patients
TAVR advocates are increasingly implanting the prosthesis inside a failed surgical bioprosthetic valve — a technique called valve-in-valve TAVR that looks promising for patients considered at high or extreme risk from open-heart surgery.
“Valve-in-valve TAVR can be a lifesaving option for these patients,” says Dr. Tuzcu, who has extensive experience with the procedure. “They should be offered the opportunity to participate in clinical studies.”
Information on valve-in-valve TAVR from three registries and from off-label use has confirmed that the size and type of prosthesis, the aortic root anatomy and the underlying pathology are important outcome determinants.
“A new valve allows only a limited opening if the size of the failed surgical prosthesis is small, and this can be an issue,” Dr. Tuzcu notes. “Additionally, some devices leave too little space between the prosthesis and the coronary arteries supplying the myocardium.”
Advances in mitral valve repair too
Although most efforts to repair the mitral valve through a catheter have failed so far, Abbott Vascular’s MitraClip® has bucked the trend, gaining FDA approval in late 2013 for treatment of severe degenerative mitral regurgitation (MR) in patients at high surgical risk. The device imitates a surgical technique called the Alfieri stitch, which improves approximation of the leaflets.
When applied to the right patient, MitraClip can provide functional and quality-of-life improvements. Cleveland Clinic performs one or two MitraClip repairs per week.
“In patients who are good surgical candidates, surgery for degenerative MR is the gold standard,” says Dr. Krishnaswamy. “For those degenerative MR patients at high risk for complications from surgery, MitraClip is a safe and effective alternative.”
Assessing MitraClip in functional regurgitation
Most European experience with MitraClip was not in degenerative MR but rather in patients with functional MR. In these patients, MitraClip can produce durable reductions in regurgitation, left ventricle size, NYHA class and heart failure admissions.
“These patients have sicker hearts,” explains Dr. Krishnaswamy. “For them, surgery is riskier and does not always produce a durable result. Having an alternative strategy is imperative, and MitraClip fulfills that need.”
The COAPT trial, which began enrolling in 2014 with Dr. Kapadia as Cleveland Clinic’s site PI, is randomizing patients with functional MR to medical therapy or MitraClip. Results should be available in two years.
About 15 additional percutaneous mitral valve repair devices are in development, but there are no plans to test them in the U.S. at this time.
The decade of transcatheter mitral valve replacement?
The next frontier may well be transcatheter mitral valve replacement (TMVR). “Whereas the past decade was the decade of TAVR,” says Dr. Tuzcu, “the coming years will be the decade of TMVR.”
Feasibility studies of several TMVR options will begin in the U.S. this year. Cleveland Clinic is participating in initial studies of the Tendyne Bioprosthetic Mitral Valve, which is implanted transapically in highly symptomatic patients with MR who are considered inoperable or at high surgical risk.
As percutaneous devices improve, transcatheter approaches may be applied to larger patient populations, although surgery remains the gold standard for treating most patients with degenerative MR.
“We perform the surgery robotically, with a small incision and no sternotomy, and achieve a nearly perfect repair in all patients,” notes cardiothoracic surgeon A. Marc Gillinov, MD. “The operative risk is 1 in 1,000.”
“The aim of the TMVR techniques is to offer options to patients who are not good candidates for surgical treatment,” adds Dr. Tuzcu.
A field in motion
With the field of transcatheter valve repair and replacement progressing quickly, Cleveland Clinic plans to remain at the fore of testing and development.
“The results of our experience have been exciting,” observes Dr. Krishnaswamy. “We’re amazed at what can be done through an almost invisible incision in the top of the thigh.”