The Year in Review and Where to Next? Interventional Cardiology 2007
The year has also provided us with more information about how best to manage myocardial infarction beyond door-to-balloon time both directly and through improved pharmacology. The prevention of renal dysfunction during interventional studies remains of high interest in our field.
Let's start with the downside of DES. To reiterate, the biggest advance in the invasive treatment of coronary artery disease in the last decade is the drug-eluting stent. DES lowered the stent-related restenosis rate and remains highly effective for treating a variety of complex lesions. However, the downside of DES was recently presented at the ACC, ESC and TCT meetings, and gives us pause about the universal application of DES with its potential for subacute thrombosis (SAT). A recent presentation at the ACC Annual Scientific Session (March 2006), from the Late Clinical Events Related to Late Stent Thrombosis After Stopping Clopidogrel (BASKET LATE) trial showed a significantly greater incidence of cardiac death or myocardial infarction (MI) in DES patients (n = 499) compared to bare-metal stent (BMS) patients (n = 244) following discontinuation of clopidogrel. Although not statistically significant, late stent thrombosis occurred twice as frequently among the DES versus BMS patients (2.6% vs. 1.3%, p = 0.23). These events occurred throughout the 12-month follow-up.
What can we conclude about the DES SAT rates and proposed relationship to the higher late mortality rates? In view of the delayed and poorly endothelialized DES, we must insure optimal mechanical stent deployment, perhaps using more IVUS, and at the same time minimize and treat the risk of platelet/thrombotic occlusion with longer duration of plavix and aspirin. Accordingly, the 2005 updated ACC/AHA PCI guidelines did not address prolonged antiplatelet regimens, but in view of the current concerns, we should consider extending clopidogrel usage for a minimum of 12 months and perhaps longer, based on empiric experience and the data indicating the late failure of endothelization of the DES. (This is in addition to the ongoing recommendation that the loading and maintenance doses of clopidogrel [300mg load, 75mg daily] and aspirin 325 mg daily be given for at least 1 month after BMS implantation [unless there is a risk of bleeding, in which case it should be given for 2 weeks], 3 months after sirolimus DES implantation, and 6 months after paclitaxel DES implantation, after which daily chronic aspirin should be continued indefinitely at a dose of 75 to 162 mg.) There will be more to come on this issue to be sure.
Catheter-based Treatment of Valvular Heart Disease
Over 250,000 patients with valvular heart disease have mitral regurgitation (MR). The treatment of MR is of high importance. Many patients with chronic heart failure (CHF) or dilated cardiomyopathy have some degree of functional mitral regurgitation, thus forming a huge patient group which may benefit by any therapy reducing mitral regurgitation, especially from a catheter-based approach. In 2006, the mainstay of MR mechanical treatment remains surgical annuloplasty and or mitral valve repair, whenever feasible.
A promising approach is that of reduction of the mitral annular circumference with percutaneous devices inserted around or under the mitral annulus to reduce the regurgitant orifice. A device placed in the coronary sinus runs parallel with the mitral annulus and when constricted, the mitral annular diameter can be shorted. However, coronary sinus annulus reduction treatments have a limited success and mixed outcome. Potential compromise of the circumflex artery with ischemia post procedure has been considered. Other devices have been placed beneath the mitral valve leaflets and seem to have some potential advantage over the coronary sinus route. Decreasing the septal to lateral wall dimensions, moving the posterior leaflet toward the septum may also improve coaptation of the mitral leaflets, and thus, reduce mitral regurgitation; however, this system is yet to be tested. It may be available within the next several years.
One of the most promising techniques is the Evalve clip, emulating the surgical Alfieri technique to reduce the mitral valve opening by clipping together the midpoint of the leaflets. The results of the phase I clinical trial of the Evalve clip, called EVEREST, been reported and show that the 6-month follow-up of the 27 patients demonstrated no procedural complications and only four major adverse events with partial clip detachment in three patients and postprocedure stroke in one.1 Surgery was performed in three additional patients who had unresolved mitral regurgitation. Thirteen of fourteen patients with reduced mitral regurgitation had maintenance of this procedure out to six months. One of the good aspects of this device is that in the event that the clip was not successfully placed, options for the surgery have not been excluded. Further studies are underway in the EVEREST phase II randomized trial comparing the clip technique with surgical valve repair or replacement. We will certainly see much more of the percutaneous valve repair techniques, not to mention the implantable aortic valve studies.
Contrast-induced nephropathy continues to be a problem in the cath lab. One potential new advance in this area involves a novel methodology to recapture injected coronary contrast from the coronary sinus before it circulates to the kidneys. Employing coronary sinus occlusion and a unique method of capturing of contrast during angiography, Myer et al report their results.2 Using quantitative fluoroscopy, an average of 70% of the contrast was captured without a complication. This novel approach to reduce renal contrast exposure may be an important adjunct in patients at high risk for contrast-induced nephropathy.
Despite being the standard of care, drug-eluting stents or any metal stents for that matter have a downside. Ideally, a stent should be placed to reduce the atherosclerotic burden, eliminate elastic recoil until the vessel wall heals and then disappear. This is the promise of a bioabsorbable stent. Bioabsorbable stents would address the issues of failure of endothelialization and late subacute thrombosis in some patients, restenosis at the edges in others, and the presence of metal within the coronary arteries with the unavoidable inflammatory reaction and impaired vessel healing after stent implantation. With the increasing use of magnetic resonance imaging and multi-slice computerized CT scanning, the presence of metal stent implants would complicate image interpretation. Late positive remodeling with vessel expansion associated with an uncovered or unopposed stent to the vessel wall would no longer be a problem if that stent could dissolve as the vessel remodels. Current research in bioabsorbable stents has made this technology feasible probably within in the next several years.
One of the most appealing bioabsorbable materials is a polymer called poly L-lactic acid (PLLA). Several stent designs have been built using PLLA mono filaments and appear to be a viable alternative to metal in some preliminary studies. Furthermore, incorporating an antiproliferative agent onto these PLLA stents in animal models suggest that this particular approach has merit. Initial human studies from Tsuji et al indicate that their bioabsorbable stent has a potential to reduce restenosis with acceptable long-term safety profiles.3 Other bioabsorbable stents include the RIVA stent which has a slide-and-lock design made of a Tyrosine-derived polycarbonate which is also radiopaque, in contrast to some of the other designs. The absorption of this particular stent material can be modified depending on its application for coronaries. The drug-coated everolimus-eluting stent of polylactic acid of bioabsorbable polymer has been examined in vivo and after 18 months, no particular stent material was found in the treated artery.
There are also bioabsorbable metallic stents made from metal alloys of iron and magnesium. Depending on the particular composition and local toxicity, absorption is related to the concentration of elements, which are removed over time. Magnesium stents are not visible on x-ray nor can they be seen on CT or MRI, and appear to be reabsorbed after the 180 days of implant. Although the concept of bioabsorbable stent is fast entering our realm for implantation, safety, absorbability and durability of the technique remain to be evaluated.
The next years should bring even more exciting prospects such as new PFO closure devices, vascular occluding plugs, drilling catheters for total occlusions, and advanced research into stem cell applications for myocardial cell preservation after infarction, to name just one of many types of new research for interventional cardiology. I hope to be able to share some these advances with you in these pages in the year to come.