Concerns and Challenges Selecting Patients for MitraClip or TAVR

Issue: March/April 2012

ByPeter C. Block, MD

At the recent Cardiovascular Research Technologies (CRT) conference in Washington, D.C., treatment options for structural heart disease took center stage, with more than a full day devoted to minimally invasive treatment of aortic and mitral valve disease.

Clinical Experience with MitraClip

As many of us know, treatment of mitral regurgitation (MR) continues to pose a dilemma of therapeutic options. The EVEREST II randomized trial now has 2 years of follow-up, and the 1-year results, showing that MitraClip (Abbott Vascular) insertion was non-inferior to surgical therapy, continue to hold. This follow-up, coupled with extension of use of the MitraClip (outside the strict criteria that governed admission into EVEREST II), has generated more and more data from the European experience and the ongoing High Risk Registry in the United States.


	Peter C. Block

The consensus is growing that for young patients with mitral valve prolapse (degenerative MR), surgical therapy (repair) has mortality of less than 1% and long-term results that are hard to beat. Strategies for use of the MitraClip have thus moved to patients with higher risk for surgical correction of MR. Patients who are becoming the best candidates for MitraClip therapy are older, have comorbidities that increase their surgical risk, or have prohibitive risk for operation. Data from the US High Risk Registry and European sites using the MitraClip have shown reduction of MR to less than 2+ in most cases, with consequent improvement in left ventricular function and NYHA class.

Perhaps most importantly, repeat hospitalizations for HF are reduced in this high-risk group, which includes patients with ischemic MR, as well as MR secondary to cardiomyopathic LV dysfunction. One problem is that, in Europe, there is commercial availability of the MitraClip, while in the United States, FDA approval is lacking and use of the MitraClip is limited to a small number of sites with continued, though limited, access to the device. The good news is that a second randomized trial called COAPT appears to be in development in the United States, which will compare extremely high-risk, non-operative patients with MR to MitraClip or ongoing medical therapy.

Lessons Learned with TAVR

Much more information is now available concerning transcatheter aortic valve replacement. More than 2 years have passed since completion of the PARTNER Trial, and interest at CRT centered on what lessons have been learned from TAVR in the United States and abroad. In addition, two major randomized trials are just beginning that will broaden our understanding of how TAVR can best be used in expanding patient populations (especially lower-risk surgical patients with aortic stenosis).

Ongoing results from the follow-up of patients from the PARTNER cohort B trial, which studied non-operative candidates with severe aortic stenosis, show that TAVR is an absolute winner over ongoing medical therapy (including balloon aortic valvuloplasty). All-cause death, CV death, NYHA class and repeat hospitalization all are “better” in patients with TAVR.

However, one of the ongoing concerns is attrition because of comorbidities. Approximately 31% of patients died at 1 year and about 43% by 2 years. Although TAVR compares favorably with an almost 70% death rate in medically treated patients at 2 years, the challenge remains in identifying which patients should be offered TAVR. For example, which 88-year-old with chronic obstructive pulmonary disease (COPD), mild renal dysfunction and LV ejection fraction of 30% will recover ventricular function and return to a “normal” existence, and which patient will not? There is still much to learn from the PARTNER cohort B trial data.

Additionally, important lessons can be learned from PARTNER cohort A, a non-inferiority trial comparing TAVR performed either by transfemoral or transapical routes to operative aortic valve replacement in high-risk operable patients. Both TAVR and surgery were associated with important, but different peri-procedural hazards: Strokes and major vascular complications were more frequent with TAVR, while major bleeding and new onset atrial fibrillation were more frequent with surgical therapy.

The consensus is that TAVR is not inferior to surgical therapy and both strategies are acceptable in high-risk patients. Differing periprocedural hazards should influence decision-making for individual patients.

Of great interest was discussion of data from the continued access registry for transapical (TA) TAVR. Those data, presented a week before at the Society for Thoracic Surgery meeting, show that the TA approach has an important learning curve. Early TA data seemed to show early mortality and stroke rates that were arguably higher than surgical therapy, but data from the continued access population now show markedly decreased all-cause mortality at 1 year, less stroke and less combined mortality and stroke. The TA approach in selected patients still seems viable.

Future TAVR Research

Two major randomized trials of TAVR are now under way, both designed to increase our understanding of TAVR use in lower-risk patients.

In the SURTAVI trial, patients will be randomized when both the cardiologist and the surgeon are in doubt as to what the best treatment is. Thus, patients at increasing lower risk for surgery can be randomized to TAVR with the CoreValve (Medtronic) device or to surgical AVR. For example, at either extreme of risk, patients likely to have a good result with surgery will be operated on, whereas those at high risk for surgery (90 years old with many comorbidities, for example) will have TAVR. TAVR could be an alternative for patients at intermediate risk for surgery, and it is this group that will be randomized. Three groups of intermediate-risk patients will be discussed for randomization by the heart team: 80-year-old patients without comorbidities; 75-year-old patients with more than one cormorbidity; and 70-year-old patients with two comorbidities. Patients younger than 70 years of age will not be randomized because of insufficient evidence on the durability of the percutaneous heart valves.

SURTAVI will randomize approximately 1,100 patients. Only experienced TAVR sites will participate. The trial will begin in 35 to 40 sites in Europe and the plan is that US sites may be added later. The primary endpoint in the SURTAVI trial is mortality and stroke, while secondary endpoints include valve failure, endocarditis, regression of left ventricular hypertrophy and pacemaker implantation rate. SURTAVI is designed to show that TAVR is non-inferior to surgery. If it is shown to be non-inferior, TAVI could be preferable for many patients with lower risk for surgery.

The PARTNER II cohort A trial, which will be conducted in the United States, is similar in design and uses a newer-generation 18F transcatheter valve (Sapien XT, Edwards Lifesciences). Patients with STS Scores as low as 4 to 6 are eligible, as are all patients with operative options. Both of these trials will show whether patients with relatively low operative risk (STS Scores of 6, for example) can have TAVR and have outcomes non-inferior to standard surgery.

One problem with both trials, however, is that we know nothing of long-term durability of TAVR valves, and we will not understand how transcatheter valve longevity compares to surgical valve replacement for many years. In addition, there is a group of patients who will be included in these randomized trials about which we already know a fair amount; for example, a 79-year-old patient with an STS Score of 9 with borderline lung function due to COPD. Data from PARTNER cohort A have already shown us that transfemoral TAVR is non-inferior to surgery for such patients. A clinician might consider the option of using the commercially available Edwards first-generation TAVR hardware (Sapien) as an alternative to surgery in a patient who might be respirator dependent post-operatively. However, the first-generation Edwards sheaths are larger than those that will be used in PARTNER II cohort A, and not all patients can have transfemoral access because of ilio-femoral atherosclerosis. To access the newer, smaller and more user-friendly devices, patients will have to undergo randomization — possibly to surgery as a lesser option.

Once again, as trials are done to evaluate new technology, we will have to struggle with whether there really is equipoise in certain parts of these trials — and as in PARTNER cohort B, we may already know the outcome.

For more information:

Peter C. Block, MD, is a professor of medicine at Emory School of Medicine, Atlanta, and a member of the Cardiology Today Intervention Editorial Board.

Disclosure: Dr. Block is an investigator in the PARTNER trials.