MAYJUNE 2008I CARDIAC INTERVENTIONS TODAYIurgical repair of a disease - PDF document

MAY/JUNE 2008I CARDIAC INTERVENTIONS TODAYIurgical repair of a diseased mitral valve hasbecome the treatment of choice for significantmitral regurgitation (MR). A series of retrospec-tive clinical studies that show that mitral valverepair, as compared to replacement, is associated with agood long-term outcome and lower mortality rate. One undersized annuloplasty ring alone or an undersized ringand an edge-to-edge repair. The study showed that theaddition of the edge-to-edge repair to an undersized annu-loplasty ring significantly improved durability of repairwithout causing significant mitral stenosis.This study,although small, gives some insight into the mechanisms ofbenefit. The apposition of the leaflets leads to effectivereduction of MR, and by anchoring the leaflets togetherthrough the chordae tendinea, it may exert a supporting,or reins, effect on the left ventricle, counteracting the pro-gression of ventricular remodeling and recurrence of MR.RESULTS OF CONVENTIONAL SURGICALOPTIONS FOR MRSurgery for MR, although effective and the current stan-dard of care, does have significant morbidity and limited sci-entific documentation of durability of MR reduction.Traditional repair may include partial leaflet resection, place-ment of an annuloplasty ring, and chordal revision orreplacement. Unfortunately, the evidence base for sho

rt- andlong-term outcomes using the various techniques is incom-plete. Most surgical literature quotes up to 90% freedomfrom reoperation at long-term follow-up, although thistends to overestimate the success rates for several reasons.First, postoperative mortality is typically not included as theprimary, and second, analysis has not been on an intent-to-treat basis. With regard to the latter, the 2007 Society ofThoracic Surgeons (STS) database, reports that as many as50% of patients with isolated mitral valve disease had pros-thetic valve replacement instead of repair, thus making itlikely that the success rates for repair are grossly overestimat-ed. It should also be noted that significant morbidity, in therange of 30%, is associated with mitral valve surgery. There is,therefore, a clinical need for a less invasive approach, as wellas a better evidence base for safety and effectiveness. DEVELOPMENT OF PERCUTANEOUS EDGE-TO-EDGE REPAIR USING THE MITRACLIPRecognizing the successful results of surgical edge-to-edge repair, it was proposed that this surgical methodcould be adapted into a percutaneous approach.1999, inspired by seeing the technique used successfullyin one of our own patients, we began work on develop-ing a percutaneous method for edge-to-edge repair,which led to the founding of Evalve, Inc. Initial attempts focused o

n reproducing the surgical para-digm of a suture-based approach. While performing preclin-ical testing in a porcine model, it was appreciated that forthe suture system to work, the leaflets needed to be stabi-lized. The stabilization system eventually evolved in an itera-tive fashion into a permanent, deployable clip known as theMitraClip device. The clip was designed to be removable andrepositionable without causing damage to the leaflets.The delivery system was refined for percutaneous place-ment in an acute porcine model, and the chronic healingresponse of the clip on the leaflets was evaluated in achronic porcine model.Chronic studies up to 1 yearconfirmed that the MitraClip became encapsulated by aMAY/JUNE 2008I CARDIAC INTERVENTIONS TODAYI Figure 3.The MitraClip device. Figure 4.Three echo views used to guide transseptal puncture.(A) Bicaval view (inferior-superior orientation) showing tentingof the fossa (arrow) (A).Short axis at the base (anterior-posterior orientation) showing tenting of the fossa (arrow) (B).Four-chamber view showing tenting of the septum for estimation of distance between transseptal puncture and site of leaflet coap-tation (C).LA,left atrium;RA,right atrium;LV,left ventricle;RV,right ventricle;AO,aorta. ABC cate information from essential transesophageal echocardio-graphic views.The procedure is perf

ormed under generalanesthesia, and a cardiac anesthesiologist plays a critical role.At various times during the procedure, the anesthesiologistmay need to cease patient respiration to allow precise posi-tioning of the clip. Manipulating the blood pressure, typicallyby increasing afterload, helps assess adequacy of the repair. PATIENT SELECTIONPatients are screened for eligibility by transthoracic andtransesophageal echocardiography. EVEREST study patientsare required to meet basic criteria for intervention from the1998/2006 American College of Cardiology/American HeartAssociation Joint Task Force recommendations regardingtherapy for valvular heart disease.Patients with moderate-ly (3+) or severe (4+) (Table 1) functional or degenerativeMR who are symptomatic, or asymptomatic but with com-promised LV function (LV ejection fraction V end-systolic dime`% ;&#xor L;w.1;nsion 40 mm), are potential candidates. Theorigin of the MR jet should be at the A2-P2 scallops. The eti-ology of MR can be either functional or degenerative.Patients with MR due to rheumatic fever or endocarditis areexcluded. An ejection fraction 25% and significant left ven-tricular dilatation (end syst .5;olic 55 mm) are other exclusioncriteria. The mitral orifice needs to measur .5;e 4 cm. Otherkey anatomic inclusion criteria include: (1) for patien

ts withfunctional MR, a coaptation length of at least 2 mm and acoaptation depth of ()or patients withleaflet flail, a flail gap lail width (Figure 7).HUMAN STUDIES USING THE MITRACLIPThe first human implant of a MitraClip was successful-ly performed on a 56-year-old woman in Caracas,Venezuela in June 2003, by a team lead by Dr. JosŽAntonio Condado. Severe (4+) MR due to bileaflet pro-lapse was reduced to h concomitant clinicalimprovement. During a 2-year period, the LVEF improved(from 48% to 52%), and the enlarged left ventricle nor-malized in size (LV inner diameters reduced from 4.6 cmto 3.6 cm). Four years after the intervention, she remainsasymptomatic and continues to have an MR grade After this first procedure, a phase 1 safety trial (EVEREST I)was initiated and successfully completed in the US. The6-month results of the phase 1 data have been published.The primary endpoint of this study was acute safety at 30days. There were no procedure-related complications; therewere four 30-day major adverse events, including partial clipdetachment in three patients, who subsequently underwentsuccessful elective surgery, and one patient who had a post-procedure stroke that resolved at 1 month.The presently enrolling pivotal multicenter EVEREST IIclinical trial is randomizing patients to MitraClip or surgicaltherapy in a 2:1 fashion.

A high-risk registry arm for patientsat significant risk for surgical morbidity and mortality (esti-mated STS score 12) has completed enrollment. Preliminary data from nonrandomized patientsenrolled in EVEREST I and in the roll-in phase of EVERESTII were presented recently.The patients had predomi-nantly degenerative or combined degenerative and func-tional disease; the remainder had pure functional MR.Acute procedural success, defined as reduction of MRseverity to 2+, was achieved in more than 75%. Lessthan 10%of patients had a major adverse event, includ-ing one death judged not to be device related. Fewpatients required surgery for complications related totransseptal puncture or the need for blood transfusionsrelated to vascular access.Partial clip detachment, defined as detachment of asingle leaflet from the clip, occurred in tients,almost all within 30 days. Detachments were not associ-ated with clinical events and did not require urgent inter-vention. The overall in-hospital mortality rate was and 30-day major adverse events including partial clipdetachment without embolization were all managedwith successful elective surgery. Length of hospital stayaveraged 2 days.For patients with suboptimal results or in whom a clipcould not be deployed, mitral repair using standard surgi-cal techniques was performed as late as 18 month

s afterthe percutaneous intervention.The percutaneousrepair did not appear to have an impact on the ability ofsurgeons to operate on the valve subsequently, a poten-tially important consideration for the eventual accept-ance of this procedure.Durability data for this procedure, admittedly midterm,now include, among patients discharged with a successfulresult, a Kaplan-Meier 2-year freedom from death, mitralvalve surgery, or recurren&#x-15.;瀀t MR 2+ rate of almost 80%.Although these initial data are compelling, the strategyfor application and indications for this procedure in thereal world remain to be determined. The degree to whichthis therapy is clinically successful will require both an ini-tial and a sustained MR reduction and, depending on thepatient population, will need to be comparable to surgicalbenchmarks. New insights will be available after the com-pletion of the randomized arm of the EVEREST II clinicaltrial. This will be the first prospective study comparingtwo different strategies for MR patients. It is also the firsttime that an independent core lab assessment of MR andLV function will be performed on a group of patientsundergoing surgical versus percutaneous valve therapy.EVEREST I and the ongoing EVEREST II randomizedtrial include patients with both degenerative and func-ICARDIAC INTERVENTIONS TODAYIMAY/JUNE