Gene Chang, MD, director of the cardiac catheterization lab at Penn Presbyterian Medical Center, reviews MR classification and pathologies, history and timeline of edge-to-edge repair, clinical trial data, and emerging therapeutic options.
Related Links:See Dr. Chang's Physician Profile
Good morning and thank you for inviting me to be a part of this program. My name is jean chang and I've been tasked with providing status update for michael valve, trans catheter edge Ted's repair or Mv tier. I am involved in a couple of research clinical trials but I don't have any financial disclosures. They start with talking about mitra vegetation. In terms of its categories or classifications of mechanisms whether be primary or degenerative M. R. Or secondary function um are in primary mar the primary problem is with the mitral valve leaflets or its apparatus. You may have a cleft or perforation, you may have excessively foot motion as we see in metro valve prolapse or a flail leaflet from a chordal rupture or restricted movement from romantic valve disease for instance in functional M. R. The primary problem is that in the myocardial and leading to annual rehabilitation or dysfunction of the leaflets but not a prime primary problem of the leaflets themselves. You may have atrial enlargement, ventricular enlargement or some sort of focal dysfunction leading to immobility or dysfunctional valve leaflet and much of vegetation. Well, tear is based on the old Alfieri stitch that was first performed in 1991. Uh The first implant of the mitral clip which is the only FDA approved product at this time for tier was in 2000 and three. There were several trials that led to FDA approval in 20 I'm sorry in october of 2013 and trials subsequently um for FDA approval for secondary M. R. In March of 2019. So primary mar in 2013. Secondary um are in 2019. Well this is the four year follow up from Everest True to which was a trial comparing open surgical repair versus per catania's therapy with mitral clip. And you can see that at four years of follow up there's really no difference in event free survival for overall survival or freedom from surgery from my agitation. On the other hand, there was much more residual metro vegetation in the tier group. So surgery still remains the gold standard FDA approval for symptomatic degenerate M. R. Was provide in 2013. As previously noted for those patients that prohibitively high risk of complications from open surgery. And you can see the sts scores for a 30 day risk of predicted risk of mortality being relatively high here. But there are limitations with the scoring system that for features that aren't taken into account for patients clearly at high risk whether they be frail have cirrhosis or severe pulmonary hypertension. And in the latest valvular guidelines for primary M. R tear is certainly considered to be reasonable for those patients that prohibited for high surgical risk. With a to a indication. What about secondary M. R. Well we all know that cooper was a trial that made a big splash at T. C. T. In 2018. This is a trial looking at comparison of medical therapy ongoing after optimal medical therapy was achieved versus device therapy with the micro clip. Corporate cutaneous edged edge repair And the you can see the first hospitalization for heart failure was reduced by about 50% In two years and mortality is reduced about 40% in two years. So significant reduction in both of these more produced mortalities. Okay. And in the valvular guidelines, all patients with secondary Marcia undergo guideline directed medical therapy. But for those that have persistent symptoms tier is reasonable. Again with a class two a indication but this is not a therapy for everybody for those patients with um that were in the Metro Fr study which is in european predominantly international trial. Again, looking at medical therapy versus brick contains therapy at one year. There was really no difference in terms of freedom from an event, whether it be survival, unplanned hospitalization for heart failure. And this begs the question why did one patients in one group get a benefit that was so pronounced in one group not receive any benefit with this device therapy? Well, when we looked at the cohorts of patients, even though their ejection fractions are about the same. Those patients, the Metro fr study clearly had lower degrees of accreditation in terms of measures or as measured by an effective reversion orifice area and smaller LV size in terms of volumes and perhaps have less refractory heart failure by NT PRO BNP level that was much lower than that seen in the coop trial. There are also more complications associated with that study and this has really led to the whole aspect of an inquiry as to can we figure out which patients will benefit which patients will not benefit with the study? Well there's this whole concept proportion versus disproportionate M. Are based on LV size, how much regurgitation, orifice or mitral vegetation would you expect to see? And those patients in the M. R. And the metro fr study were more proportionate compared to those patients in the cohort study where they had much more M. R. Than one would have predicted by the LV size and dysfunctional loan. And this is basically led to a lot of investigation for patient selection in the future. With this therapy going back to the importance of looking at the phenotype in terms of not only class but the phenotype within the class that may benefit. May identify those patients that would benefit from this therapy. There are emergent treatment strategies with other edge gets repaired devices, quartile apparatus repair direct and indirect. Annual plastic and contains much about replacement which I won't talk about right now because we have another case study and discussion ongoing. But this is another device. It's the Edwards device or pascal that's being looked at in class two D. Two F. Here within the health system. There is a trance a pickle approach to look at P. Two prolapse and artificial court implantation that's also being looked at in the health system. And I'm really excited about this other study for the empowered trial which is a Caroline device. It's a night and all device that's placed in the corner sinus with a distal and proximal anchor to cinch the metro poster of mitral leaflet and reduce metro vegetation. And we're excited because we just enrolled our first patient in this last week. In conclusion for primary mar surgical repair. I do want to stress this remains as the optimal intervention. But trans catheter edge dent repair is indicated for patients at high or prohibited search risk or even an inoperable status with STS scores is noted for secondary M. R. Would consider Edge did repair following a heart team approach and that should really be identified in terms of heart multidisciplinary approach for all of our therapies, but for those patients having persistent symptoms after optimal medical therapy and that does include bio ventricular pacing, the assessment of the anatomy of the mitral valve pathology and the mechanism of the micro vegetation is crucial in evaluating tier candidacy and the outcomes. I think I believe in these patients there are emerging therapeutic options on the distant horizon but will be a while before they come into the mainstream. Thank you