- Email: [email protected]
A pathoanatomic approach to the management of mitral regurgitation
TR
E N D S I N
C
A R D I O V A S C U L A R
M
E D I C I N E
] (2015) ]]]–]]]
Available online at www.sciencedirect.com
www.elsevier.com/locate/tcm
A pathoanatomic approach to the management of mitral regurgitation Vinay Badhwarn, Anson J.C. Smith, and João L. Cavalcante The Center for Mitral Valve Disease, Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA
abstra ct Mitral regurgitation remains the most common global valvular heart disease. From otherwise unsuspecting healthy patients without overt symptoms to those with recalcitrant heart failure, mitral valve (MV) disease touches millions of patients per year. While MV prolapse without regurgitation remains benign, once regurgitation begins, quantification of severity is related to prognosis. Understanding the mechanism of regurgitation guides appropriate treatment. Current management guidelines emphasize early therapy after careful assessment of both anatomy and severity of mitral regurgitation. The objective of this review is to provide an update on the treatment of MV disease and to offer additional granularity on pathoanatomic decision making that may aid a more precise application of optimal guideline-directed therapy of primary and secondary mitral regurgitation. Key Words: Mitral valve disease, Mitral regurgitation, Diagnosis, Management, Surgery. & 2015 Elsevier Inc. All rights reserved.
Mitral regurgitation represents the most common valvular disease affecting more than 2 million people in the United States [1]. From otherwise unsuspecting healthy patients without overt symptoms to those with recalcitrant heart failure admissions, MV disease touches millions of patients per year. The structural ideal that “form ever follows function” harmoniously guides the accurate assessment and clinical management of MV disease. Mitral valve prolapse without regurgitation remains benign, but once regurgitation is present the quantification of severity and left ventricular function become important, as they are associated with prognosis. Current management guidelines emphasize early therapy after careful assessment of both anatomy and severity of mitral regurgitation. The objective of this review is to provide an update on the treatment of MV disease and to offer additional granularity on pathoanatomic decision making that may aid a more precise application of optimal guideline-directed therapy.
The increased prevalence of MV disease coupled with several recent advancements in surgical and catheter-based treatment has resulted in a progressive rise in the number of corrective MV interventions performed annually [1,2]. Although there have been exciting developments in catheter-based interventional therapy to minimize mitral regurgitation (MR), these options are currently reserved for frail complex patients with prohibitive surgical risk. The application of a multidisciplinary heart team approach to the diagnosis and management of mitral pathology enhances the evidence-based team approach to direct optimal pathoanatomically appropriate treatment for each patient. We will review the diagnosis and optimal surgical treatment of mitral valve disease as well as note emerging options for interventional management. Together with technical developments in the proficiency and reproducibility of MV repair, the recent progress in preoperative pathoanatomic imaging precision has led to a substantial increase in the number of successful repairs.
The authors have indicated there are no conflicts of interest. n Corresponding author at: Presbyterian University Hospital, 200 Lothrop St, C-700, Pittsburgh, PA. Tel.: þ412 648 6314; fax: þ412 692 2184. E-mail address: [email protected] (V. Badhwar). http://dx.doi.org/10.1016/j.tcm.2015.05.007 1050-1738/& 2015 Elsevier Inc. All rights reserved.
2
T
R E N D S I N
C
A R D I O V A S C U L A R
ME
D I C I N E
] (2015) ]]]–]]]
10,000 9,000 8,000 7,000 6,000 5,000
Mitral Valve Repairs Mitral Valve Repair + CABG Mitral Valve Replacements
4,000 3,000
Mitral Vavle Replacements + CABG Mitral Valve Replacement + AVR
2,000 1,000 0
Fig – Trends of mitral valve surgery in the United States. There has been a doubling of the frequency of mitral valve repair performed over the last 10 years. The rates of isolated mitral replacement have also risen but not to the degree of mitral repair. (Source: The Society of Thoracic Surgeons National Adult Cardiac Surgical Database.) According to the Society of Thoracic Surgeons (STS) National Adult Cardiac Surgery Database, 8662 isolated MV repairs were performed in the last year alone. This represents a 100% increase in just the last decade. In addition, in 2013, there were 4733 MV repairs combined with coronary revascularization, 6554 isolated MV replacements, and 2413 replacements with coronary revascularization (Fig.). The 2014 AHA/ACC Guidelines for the Management of Patients with Valvular Heart Disease recently updated several aspects pertaining to surgical intervention for MV disease [3]. For primary mitral regurgitation (MR), or degenerative disease, MV repair remains the preferred treatment with increasing options for rheumatic disease. Though management of secondary or functional MR remains a challenge, the importance of surgery is emphasized. Surgery remains an integral part of MV disease management and recent improvements in outcomes, access, and surgical techniques have enabled earlier referral for definitive therapy.
Mitral valve pathoanatomy Though MRI and CT are important evolving tools for the assessment of MR and ventricular function, echocardiography remains the primary diagnostic method of choice to aid decision making in mitral valve disease [4–6]. Though much recent focus has been on methods to quantitatively assess MR severity especially in appropriate loading conditions, another key to outcome-directed mitral valve treatment is a detailed pathoanatomic assessment [7–9]. Once the presence and severity of MR have been established (Table 1), clear identification of the etiology and mechanism of MR is of critical importance. This serves to not only aid decision making as to where and when to refer for surgery, but also it provides the primary strategic surgical roadmap toward successful repair. Recent advances in three-dimensional echocardiography now permit clear identification of causative etiology and surgical planning well in advance of entering the operating room. It is therefore of increasing importance that the contemporary MV surgeon possess an in-depth knowledge of MV echocardiographic imaging and
interpretation. Likewise, it is equally important that referring cardiologists understand the various surgical techniques available and how to provide views of the valve to optimally aid in planning therapy. For example, the recent advent of the MitraClip (Abbott Cardiovascular, Abbott Park, IL) that enables the percutaneous delivery of an edge-to-edge mitral leafletsecuring device requires a very specific mitral pathoanatomy to be applicable—most commonly for A2–P2 defect or where there is coaptation loss at the middle of the 2 leaflets. A very well done transthoracic echocardiogram (TTE) can serve to outline most of the mechanism of MV disease. The majority of surgical repair planning can be done with 4 clear views of the mitral valve from conventional twodimensional transesophageal echocardiography (TEE): the mid-esophageal 4-chamber, long-axis 2-chamber, midcommissural 2-chamber, and the basal short-axis view. Though color Doppler mapping setting at a standard Nyquist of 50– 60 cm/sec is helpful to confirm MR mechanism, surgical planning and diagnosis of pathoanatomy is best assessed without color in each of these 4 views. If available, three-dimensional assessment with TEE using surgical “en face” view may be helpful to confirm primary etiology. Three-dimensional TEE can also be helpful in equivocal cases to derive vena contracta area, which is not dependent on any flow or geometric assumptions and has good volumetric correlation with cardiac MRI [4]. It can
Table 1 – Echocardiographic quantitative parameters for severe mitral regurgitation. I. Vena contracta width 40.7 cm II. Systolic flow reversal in the pulmonary veins III. Effective regurgitant orifice area 440 mm2 IV. Regurgitant volume 460 mL V. Regurgitant fraction 450% VI. Prominent flail leaflet or ruptured chordal apparatus Supportive signs: large wall-impinging regurgitant jet (Coanda effect); a large central regurgitant jet (440% of LA), E-wave dominant mitral inflow (E 4 1.2 m/s); severe LA enlargement (especially in setting of normal LV function) Adapted from Grayburn P. Heart 2008;94:376–383.
T
R E N D S I N
C
A R D I O V A S C U L A R
be particularly useful in secondary MR pathology (functional/ ischemic), as the effective regurgitant orifice often extends across the leaflet coaptation and is underestimated by current 2D methods such as the proximal isovelocity surface area. While not critical to primary surgical planning in severe MR, 3D TEE is most useful to finally plan for nuances of repair by focusing attention to potential trouble spots that may not have been clearly detected on 2D imaging such as clefts, commissural pathology, and calcium encroachment of the leaflets that might impact a resection or non-resection repair strategy. High-quality echocardiographic analysis can provide up to 97.8% concordance between preoperative assessment of reparability and successful operative repair [9]. Finally, the use of comprehensive preoperative and postoperative TTE, and intraoperative TEE assessment for all mitral operations is the current standard of care. The contemporary heart team approach to mitral disease involves an in-depth understanding of pathoanatomy to appropriately apply guideline-directed treatment. A collective understanding of terminology is important, as in the commonly used Carpentier classification of mechanism [Type I— normal leaflet motion, annular dilation, and leaflet perforation; Type II—leaflet prolapse, chordal rupture, chordal elongation, papillary muscle rupture, or elongation; Type III— restricted leaflet motion during diastole (IIIa) or systole (IIIb)]. The surgical relevance of leaflet-based primary MR pertains to the sub categorization of degenerative myxomatous disease and fibroelastic deficiency, as well as to the quite different rheumatic pathologies. Secondary or functional MR related to non-leaflet-based etiologies associated to ischemic or dilated myopathies provides an entirely different set of variables when evaluating surgical or interventional options. Surgical approach and timing based on pathoanatomy of primary and secondary MR will be reviewed.
Primary mitral regurgitation Primary MR involves the surgical spectrum from focal mitral prolapse in the setting of an otherwise anatomically normal mitral valve, known as fibroelastic deficiency, to a disease state of myxomatous degeneration manifested by diffuse excess tissue, its zenith being Barlow's disease. The surgical approach to each level of this spectrum is different and pathoanatomically directed. Finally, rheumatic MR is at the opposite end of this spectrum manifested by diffuse leaflet and subvalvular thickening, as well as commissural fusion. The surgical approach is also quite different. While these will be outlined by distinct disease state, it is important to note that in some cases pathoanatomic markers from each of these causes of primary MR may occur simultaneously in 1 patient.
Fibroelastic deficiency First described by Carpentier et al. [10], fibroelastic deficiency is a focal fibrillin deficiency, most commonly affecting the medial posterior (P2) scallop and associated with overall thin leaflet tissue and focally ruptured primary chordae. The remainder of the valve leaflet tissue may be normal or even translucent with relatively normal non-dilated annular dimensions at presentation [11]. Patients are often older and have an abbreviated
ME
D I C I N E
] (2015) ]]]–]]]
3
clinical presentation. This often focal pathology affords a focal surgical solution. Limited triangular resection of the pathology or a polytetrafluoroethylene (PTFE) neochordal support followed by an annuloplasty is most commonly and very successfully applied via conventional sternotomy or minimally invasive and robotic approaches [12].
Myxomatous degeneration The next step on the cascade of degenerative primary MR involves a progression of disease with development of excess leaflet tissue secondary to mucopolysaccharide accumulation in leaflet mucosa. As this degenerative process involves the majority of the posterior leaflet, the P2 scallop can develop excessive tissue and length. The thickness and chordal elongation of the primary chords often result in rupture. Adjacent leaflet components also commonly manifest excess tissue and there is often associated moderate annular dilatation at presentation. The progressed state of myxomatous degeneration involving more than just the P2 scallop of the posterior leaflet is known as forme fruste [13]. These patients often present at younger ages with a longstanding history of MV disease. Anterior leaflet involvement may occur, but this is often focal. This more classic form of mitral prolapse leading to regurgitation requires pathology-directed surgical treatment to often decrease posterior leaflet height and restore leaflet coaptation while preserving leaflet motion (Table 2). Carpentier's classic quadrangular resection with or without a posterior sliding valvuloplasty [13] has long been applied to this pathology. However, depending on the extent of excess tissue, contemporary simplified surgical techniques may involve focal triangular resection with or without ipsilateral posterior chordal transfer [14,15], a non-resection technique using multiple PTFE neochordae only [16,17], modified posterior butterfly-like leaflet resection to decrease posterior leaflet height [18], or even posterior leaflet ventricular anchoring with PTFE [19]. Of course, any combination of these recent techniques could be applied depending on the pathology in order to achieve coaptation restoration and the avoidance of systolic anterior motion (SAM). These surgical techniques may be applied successfully via sternotomy or minimally invasive and robotic approaches depending on surgical experience (Table 3).
Barlow's disease When myxomatous change and excess leaflet tissue is diffuse and extensively involves both leaflets, it is characterized as bileaflet prolapse associated with Barlow's disease [20]. Similar to other forms of myxomatous degeneration, Barlow's patients often present under the age of 60 years with a protracted history of mitral valve prolapse or murmur. Echocardiographically, these often have very large posterior and anterior leaflets with mid-systolic failure of coaptation above the Table 2 – Primary objectives of mitral valve repair. I. Restore leaflet coaptation depth to 45 mm II. Stabilize and remodel the mitral annulus III. Preserve or restore normal leaflet motion IV. No more than mild regurgitation on immediate postoperative echo
4
T
R E N D S I N
C
A R D I O V A S C U L A R
ME
D I C I N E
] (2015) ]]]–]]]
Table 3 – Common contemporary surgical techniques. Primary mitral regurgitation (I) Non-resection techniques using Gore-Texs neochord reconstruction with annuloplasty May be used for focal leaflet flail or bileaflet prolapse May be used for forme fruste diffuse posterior leaflet myxomatous disease May be used for isolated anterior leaflet prolapse
(II) Focal triangular resection with annuloplasty
May be used for focal leaflet flail of the posterior or commissural leaflet
(III) Sliding leaflet valvuloplasty with annuloplasty
May be used for forme fruste diffuse posterior leaflet myxomatous disease May be used in the setting of bileaflet prolapse with excess posterior leaflet May be used in any of the above with significant echocardiographic predictors of systolic anterior motion
Secondary mitral regurgitation
(I) Restrictive remodeling rigid annuloplasty
May be used as primary modality for annular dilatation mechanism May be used in conjunction with secondary or tertiary chordal cutting May be used in conjunction with other adjunctive procedures (i.e., papillary muscle sling)
(II) Chord-sparing mitral valve replacement
May be used as primary modality for annular dilatation with severe leaflet tethering (i.e., 410 mm tenting height)
annular plane, often with multiple MR jets. The excess leaflet scalloping is often associated with pronounced clefts between each posterior scallop. The surgical hallmarks are that of billowing leaflets of excess tissue and a very large mitral annulus often greater than 40 mm at presentation. The surgical strategy may involve many of the techniques outlined earlier but often involves closing clefts, decreasing posterior leaflet height by resection or non-resection techniques, and a large annuloplasty. Patients over the age of 60 years with Barlow's may often have posterior mitral annular calcification (MAC). This may further augment repair complexity, and thus its preoperative identification will assist in navigating this either by resection and leaflet re-implantation [21] or by nonresection methods. Depending on the extent of the mitral pathology, these patients often require surgeons with experience in advanced mitral repair techniques. Results with traditional resection techniques, PTFE neochordal reconstruction, and many contemporary advancements in mitral repair, have consistently been excellent when applied correctly [22–28]. Long-term freedom from mitral regurgitation and reoperation is between 80% and 90%. Clearly, not all patients with severe primary degenerative MR are the same, and thus the value in a preoperative pathoanatomic diagnosis by echocardiography cannot be overstated. When combined with the patient's age and comorbidities, and the center's or surgeon's experience with mitral repair, general knowledge of MR etiology may aid more precise treatment planning. Individual surgeon experience is a known factor for success in mitral repair. There is nearly a 3-fold likelihood of repair when experience is over 100 cases per year compared to 5–10 per year, with a threshold for frequency of success being over 50 cases per year [29,30]. However, these registry estimates lack the pathoanatomic granularity of the mitral disease states going to surgery. As guideline-directed referral for mitral repair is considered for symptomatic patients, the majority of actively practicing cardiac surgeons with good clinical outcomes performing
over 10 repairs per year should be able to successfully repair straight forward posterior leaflet pathology associated with fibroelastic deficiency or uncomplicated focal myxomatous degeneration. However, if the patient is asymptomatic, if the mitral pathoanatomy is more complex, or if a minimally invasive or robotic approach is desired, consideration for experienced surgical referral is warranted to align with the Class IIa recommendation of a heart valve center of excellence with o1% mortality and where a 495% chance at repair may be attainable [3,11].
Timing of surgery for primary degenerative mitral regurgitation As our knowledge gaps on the natural history of uncorrected and corrected severe primary MR have closed in recent years, the concept of “watchful waiting” [31] has ceded to the guideline-supported principles of early surgical referral even in asymptomatic patients [32–35]. This concept has now extended to older individuals who were once relegated to referral only when augmented symptoms existed. Evidence supporting long-term outcome improvement with MV repair has prompted guideline-directed early referral for severe mitral regurgitation to be applied at all age ranges [35,36]. Moreover, regardless of age at the time of successful MV repair, patients can be expected to attain longitudinal survival equivalency to their normal age-matched population [1,23,36].
Outcome predictors following surgery for primary mitral regurgitation For asymptomatic patients with severe MR (Table 1), it may be difficult to know when to refer for surgery, or how to predict the left ventricular (LV) functional response to repair in those with pre-existing LV dysfunction. Brain natriuretic peptide (BNP) levels can serve as a marker of early LV dysfunction. In asymptomatic patients with severe MR, Pizarro et al. [37] found
T
R E N D S I N
C
A R D I O V A S C U L A R
BNP to be a strong independent predictor of late heart failure or death. This early evidence demonstrates that while low BNP levels o105 pg/mL were associated with stable mitral disease, higher levels may be predictive of an unfavorable outcome from severe MR. Thus, BNP may be adjunctive in the assessment of referral timing for asymptomatic patients [8,37]. Recently, speckle tracking two-dimensional strain echocardiography has emerged as a promising technique to detect latent LV contractile impairment occurring early in subendocardial layers. In severe degenerative MR, disproportionately higher LV global longitudinal strain may signify a maladaptive preload-related change that is associated with substantial loss of LV function immediately after MV repair. Preoperative assessment of global longitudinal strain may be potentially useful for optimizing the timing of surgery for degenerative primary MR [38,39]. Dynamic changes in degenerative/primary MR that can be brought on with exercise appear to have an important role [40]. For example, assessment of the MR severity, pulmonary artery systolic arterial pressure, LV contractile reserve with global longitudinal strain [41], and right ventricular function [42] during exercise echocardiography, all appear to have incremental prognostic value over standard baseline assessment. Finally, quality control of intraoperative repair is of critical importance, as any occurrence of more than mild MR is predictive of a poor longitudinal outcome and an increased incidence of reoperation [43]. Thus, if greater than mild MR is identified on the postoperative TEE, immediate correction is recommended.
Rheumatic mitral regurgitation Rheumatic heart disease remains a prevalent problem in non-Western countries resulting from an autoimmunemediated inflammatory process triggered by exposure to group A streptococcus [44]. More common in children, this process attacks the mitral valve most commonly. The inflammatory process affects multiple tissue layers and transforms into fibrosis over time. Valvular fibrosis may be exacerbated by recurrent inflammatory reactions during repeat episodes of rheumatic fever. Fibrosis impacts both the mitral valve tissue as well as the subvalvular apparatus by increased tissue thickness, gradual retraction and deformation, and subsequent predisposition to calcification and stenosis. Though pure regurgitation can be seen, the resulting chronic mitral valve dysfunction commonly manifests as mixed stenosis and regurgitation. Rarely, the inflammatory process itself can be the origin of acute mitral valve regurgitation due to myocarditis and subsequent LV dysfunction or by way of rupture of weakened primary chordae. The common manifestations of late rheumatic MR seen in the United States occur with the pathoanatomic hallmarks of leaflet thickening, fibrotic subvalvular foreshortening, and commissural fusion. If prosthetic-related anticoagulation is questionable and repair is felt to be durable, rheumatic repair consideration is a IIb indication. Surgical correction may require a multitude of techniques that may include leaflet thinning, commissurotomy, chordal resection, PTFE neochords, and annuloplasty. Results of these techniques when performed in experienced centers have been equivalent to prosthetic replacement in terms of durability and outcomes [45,46]. The
ME
D I C I N E
] (2015) ]]]–]]]
5
fibrotic extension of rheumatic pathology is mitral stenosis. In this setting, leaflet augmentation of the posterior leaflet or anterior leaflet when combined with bi-commissural release may provide a non-resection method for a potentially more reproducible repair [47]. When contemporary techniques for rheumatic mitral repair are applied, results in experienced centers can be as good as with degenerative repair [48].
Secondary mitral regurgitation Functional MR secondary to a non-ischemic or ischemic etiology is a disease spectrum that also requires a pathoanatomic approach to discern optimal therapy. In non-ischemic dilated myopathies, the alterations to mitral anatomy stems on a global alteration to ventricular dynamic function with diffuse non-segmental papillary muscle displacement and secondary multi-segment MV leaflet tethering. In functional ischemic MR, segmental alterations in LV function result in post-infarct or post-ischemic event LV remodeling. This in turn leads to initial segmental papillary muscle displacement and regional focal leaflet tethering. This is most commonly associated with posterior papillary muscle fibrosis and displacement. If left untreated or unrecognized, secondary alterations to LV wall stress result in a global alteration in ventricular dynamic function followed eventually by diffuse papillary muscle displacement and multi-segment leaflet tethering. In functional ischemic MR, the results with any form of treatment are inversely proportional with the severity of LV remodeling. As the degree of LV remodeling and MV tethering progresses along this cascade, surgical options to correct MR also must selectively adapt. The broad argument of repair versus replacement cannot be applied for all functional ischemic MR patients, as this is a disease continuum. For many patients early in the spectrum of secondary functional MR, restrictive annuloplasty remains a durable solution with good mid-term outcomes and quality-of-life improvement [49–51]. When surgery for ischemic functional MR is studied as a single-broad pathoanatomic entity, MV repair has nearly half of the operative mortality of MV replacement, but the 5–6-year survival is similar [51–53]. In a recent multicenter randomized trial on MV repair versus replacement for functional ischemic MR, Acker et al. [54] reported similar results. Mitral repair had half of the operative mortality and composite adverse event end points in the first 30 days, but the 1-year outcomes in postoperative survivors were similar. However, notable in this study was a 33% rate of return to moderate-severe MR 1 year following restrictive annuloplasty repair. They concluded that both restrictive annuloplasty and MV replacement were equivalent in the degree of reverse LV remodeling, adverse events, quality of life, and survival at 1 year but advocated that mitral valve replacement is an acceptable treatment option in this population. Though this is one of the rare randomized controlled trials performed in cardiac surgery, this study randomized patients only by MR grade alone instead of pathoanatomy such as degree of tethering, and they defined severe MR as an EROA 4 40 mm2 instead of perhaps the more appropriate, yet still controversial, 420 mm2 for functional MR, as supported in
6
T
R E N D S I N
C
A R D I O V A S C U L A R
the current European guidelines [3,55]. Furthermore, as one interprets this study, it is important to note that if the patients in this trial who had late MR following repair were excluded, those with a successful MV repair had a 22.6% reduction in left ventricular volumes compared to only a 6.8% reduction after MV replacement [56]. This highlights the lack of anatomic granularity in this study and further supports that a more pathoanatomic basis for treatment of this complex disease spectrum is required. To determine the pathoanatomic thresholds for surgical decision making in functional MR, one can examine specific outcome deficiencies with repair. When ventricular dilatation and mitral tethering is severe, outcomes are poor. We know that when the tenting height is greater than 10 mm below the annular plane, inter-papillary muscle distance is greater than 20 mm and the LVEDD is greater than 65 mm, outcomes with restrictive mitral annuloplasty alone are suboptimal and plagued with a higher rate of recurrent MR [55,56]. If annuloplasty is to be attempted, results in non-ischemic patients are superior to those with an ischemic MR etiology, and purely flexible rings or bands are prone to late failure and should not be utilized in functional MR [56]. Therefore, if we follow a pathoanatomic approach to treat functional MR, favorable anatomy for MV repair includes a tenting height of 1 cm or less, a LVEDD of less than 65 mm, and an interpapillary distance of less than 20 mm. In this subgroup, one could expect an acceptable result with reasonable durability and low operative mortality. Of interest, post hoc analysis of the patients who received MV repair in the recent multicenter randomized study [54] revealed 2 important findings: (a) MR recurrence occurred early after surgery (i.e., within 30 days) and mostly moderate in severity and (b) none of the former imaging parameters mentioned before held up in the multivariate model, except for basal aneurysm/dyskinesis. The authors subsequently emphasized that residual tethering post-MV repair is a potential mechanism of MR recurrence in these patients [57]. In this context, we believe that larger studies with detailed phenotyping using multimodality imaging of the pathoanatomic characteristics of these patients will be necessary to better inform best practice for tackling this complex entity. Chord-sparing MV replacement is clearly an acceptable surgical solution for functional MR, particular in the more extreme states of ventricular dilatation and MV leaflet tethering as just outlined. However, there are other contemporary adjunctive solutions that are available to be considered when the pathoanatomy is not within favorable parameters for restrictive annuloplasty alone. These adjunctive valvular or subvalvular procedures to restrictive annuloplasty include anterior or posterior leaflet augmentation [58,59], intra-ventricular papillary muscle surgical relocation [60], and papillary muscle sling implantation [61,62]. These additive mitral repair strategies have shown promising early- and mid-term results and may be integrated into the armamentarium of surgeons experienced in mitral repair. The objective of these supportive procedures in conjunction with annuloplasty is to optimize tethering geometry by altering the chordal stress–strain relationship between the mitral leaflets and ventricle [63]. The clinical decision on how to surgically treat ischemic functional MR is not solved in a debate over broad repair versus
ME
D I C I N E
] (2015) ]]]–]]]
replacement superiority. It is evident from the current literature that both options can be successfully applied. Rather, the future exists in improvements in the granularity of preoperative pathoanatomic identification of those in whom repair would be successful versus those who would benefit from replacement. In equivocal cases, cardiac MRI may become a useful tool to simultaneously assess MV tenting area, LV volumes, sphericity, scar size, location, and papillary muscle involvement. In a similar analogy to the spectrum of primary MR, reduction annuloplasty can be easily standardized and reproduced by any cardiac surgeon performing mitral operations, but complex subvalvular or valvular adjunctive maneuvers are likely best performed by surgeons well versed in these techniques. Coupled with patient factors, preoperative echocardiographic analysis will ultimately identify those patients who can be managed with annuloplasty alone, those who may require reference center MV repair, and those who should be directed toward MV replacement. Particularly in secondary MR, patients at high or prohibitive risk for surgery may be ideally suited for interventional therapy such as the MitraClip. The ongoing trial on Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy (COAPT) for extremely high-surgical-risk patients hopes to determine if there is clinical equipoise in managing these difficult patients.
Interventional mitral therapy When surgery is of prohibitive risk, there are new options for patients on the horizon to manage symptomatic mitral valve disease. There have been several innovations in percutaneous mitral therapy that have brought this into active clinical application. Two new trans-apically implanted catheterbased mitral replacements have seen very early first-in-man clinical experience. Given the anatomical proximity between the mitral and aortic valves, pre-clinical technological developments were necessary to avoid LV outflow tract (LVOT) gradient and/or aortic valve dysfunction [64]. The Tiara pericardial bioprosthetic device (Neovasc Inc., Vancouver, Canada) has a unique D-shaped geometry to fit the asymmetric annulus and 3 anchoring structures into the trigons and posterior shelf of the MV annulus. In pre-clinical and limited published case series, the Tiara device demonstrated good hemodynamics without left ventricular outflow tract obstruction [65]. The Fortis device (Edwards LifeSciences, Irvine, CA) is a similar bovine pericardial bioprosthesis, which has a self-expanding nitinol framed device a slightly higher profile [66]. Use of pre-procedural CT scan for detailed screening of the anatomic suitability is mandatory to avoid potential dynamic LVOT obstruction produced by subvalvular apparatus inclusive of systolic anterior motion of the anterior MV leaflet. At this time, the clinical experience is very limited [66], but ongoing developments will provide further insights into the potential applicability of this device. Coronary sinus devices have been attempted percutaneously with the goal to change the anterior–posterior dimension by displacing the posterior mitral valve leaflet forward, potentially improving leaflet coaptation and reducing mitral regurgitation severity. One of the concerns is the close relationship between the left circumflex artery and the CS and the
T
R E N D S I N
C
A R D I O V A S C U L A R
Table 4 – Anatomic eligibility criteria for MitraClip. Criteria
Optimal valve morphology
Pathoanatomy of regurgitation Leaflet calcification Mitral valve opening area (cm2) Posterior leaflet mobile length (mm) Coaptation depth Leaflet thickness and mobility Myxomatous disease leaflet flail considerations
Central pathology between A2 and P2 segments None Z4 cm2 Z10 mm o11 mm Normal Classical isolated MR prolapsed, flail size o15 mm and flail gap o10 mm
potential for coronary impingement, stenosis/injury. In most patients, the CS courses superiorly to the mitral annulus, whereas the circumflex artery courses between the CS and the mitral annulus in 68–97% of the patients, depending on the coronary dominance. These anatomic considerations have limited the wide applicability of coronary sinus devices. Multi-dimension CT may provide useful information in eligibility and selection of potential candidates for percutaneous mitral annuloplasty via the coronary sinus approach [67]. However, the one with largest experience to date (nearly 17,000 patients worldwide as of the beginning of 2015) and most commonly used interventional approach to MR remains the MitraClip system, which is peripherally inserted via the femoral vein and delivered by trans-septal approach [68]. The MitraClip system has demonstrated adequate procedural safety with good short- and intermediate-term success and low mortality [69,70]. Favorable results from the EVEREST II trial in USA have led to the device approval by the FDA in 2014 for patients with primary/degenerative MR of prohibitive surgical risk where a heart team approach including a surgeon expert has deemed the patient pathoanatomically suitable [71]. While the ideal anatomy for the MitraClip involves the malcoaptation of the A2–P2 segments of the leaflets, there is emerging European experience with successful treatment of more medial or lateral defects in select cases [72,73]. The COAPT clinical trial, designed as a noninferiority study to medical management, hopes to determine the ideal patient selection in inoperable cases of secondary MR. Strict selectionbased anatomical criteria and thorough intra-procedural guidance with transesophageal echocardiography are essential for the successful delivery of this new therapy (Table 4) [74].
Summary Recent technical advancements in the surgical management of mitral valve disease endeavor to more reproducibly adhere to the principles of restoration or preservation of leaflet motion, annular integrity, and coaptation depth. Together with improvements in medical management, valve imaging, and a growing trend toward more durable and minimally invasive repairs, the paradigm of how we manage mitral valve disease is substantively evolving. The recent 2014 AHA/ACC Valvular Management guidelines [3] echo these developments. The prevailing trend
ME
D I C I N E
] (2015) ]]]–]]]
7
toward MV repair as the standard of care for primary severe MR has changed mitral disease from a condition in which we respond to late complications such as atrial fibrillation, pulmonary hypertension, and ventricular remodeling, into one in which we proactively treat prior to the natural development of these sequelae. It is clear that earlier surgical intervention for severe MR, even in asymptomatic patients, provides longitudinal quality of life and survival benefits. With increasing surgical education and proliferation of MV repair expertise, patients will continue to benefit from more access to centers of excellence. Access to advanced surgical or interventional therapies should be in the form of a multidisciplinary heart team environment with specialized surgeons, interventionalists, and imagers focused on all aspects of mitral valve disease. Both cardiology and cardiothoracic surgical communities must continue to stringently investigate rapidly developing techniques as a unified consortium as we together close the knowledge gap in mitral disease. This form of partnership will assure the safe development of new therapeutic options for mitral pathologies while supporting wider patient access focused on maintaining the highest standards-of-quality outcomes.
refere nces
[1]
Enriquez-Sarano M, Akins CW, Vahanian A. Mitral regurgitation. Lancet 2009;373:1382–94. [2] Gammie JS, Sheng S, Griffith BP, Peterson ED, Rankin JS, O'Brien SM, et al. Trends in mitral valve surgery in the united states: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Ann Thorac Surg 2009;87: 1431–7. [3] Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/ American Heart Association task force on practice guidelines. J Am Coll Cardiol 2014;63:2438–88. [4] Thavendiranathan P, Phelan D, Thomas JD, Flamm SD, Marwick TH. Quantitative assessment of mitral regurgitation: validation of new methods. J Am Coll Cardiol 2012;60: 1470–83. [5] Grayburn PA, Weissman NJ, Zamorano JL. Quantitation of mitral regurgitation. Circulation 2012;126:2005–17. [6] Monin JL, Dehant P, Roiron C, Monchi M, Tabet JY, Clerc P, et al. Functional assessment of mitral regurgitation by transthoracic echocardiography using standardized imaging planes diagnostic accuracy and outcome implications. J Am Coll Cardiol 2005;46:302–9. [7] Pepi M, Tamborini G, Maltagliati A, Galli CA, Sisillo E, Salvi L, et al. Head-to-head comparison of two- and threedimensional transthoracic and transesophageal echocardiography in the localization of mitral valve prolapse. J Am Coll Cardiol 2006;48:2524–30. [8] Bergler-Klein J. Global longitudinal strain for predicting outcome after mitral repair or cardiac surgery: here to stay? Eur Heart J Cardiovasc Imaging 2013;14:12–4. [9] Drake DH, Zimmerman KG, Hepner AM, Nichols CD. Echoguided mitral repair. Circ Cardiovasc Imaging 2014;7:132–41. [10] Carpentier A, Lacour-Gayet F, Camilleri J, Dubost C. Fibroelastic dysplasia of the mitral valve: an anatomical and clinical entity. Circulation 1980;62:207. [11] Adams DH, Rosenhek R, Falk V. Degenerative mitral valve regurgitation: best practice revolution. Eur Heart J 2010;31: 1958–66.
8
[12]
[13]
[14] [15]
[16]
[17]
[18]
[19]
[20] [21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
T
R E N D S I N
C
A R D I O V A S C U L A R
Suri RM, Schaff HV, Meyer SR, Hargrove WC. Thoracoscopic versus open mitral valve repair: a propensity score analysis of early outcomes. Ann Thorac Surg 2009;88:1185–90. Carpentier A, Chauvaud S, Fabiani JN, Deloche A, Relland J, Lessana A, et al. Reconstructive surgery of mitral valve incompetence: ten-year appraisal. J Thorac Cardiovasc Surg 1980;79:338–48. Glower DD. Surgical approaches to mitral regurgitation. J Am Coll Cardiol 2012;60:1315–22. Schaheen LW, Hayanga AJ, Wei LM, Badhwar V. Chordal transfer for repair of anterior leaflet flail: a reproducible option. Multimed Man Cardiothorac Surg 2014;2014, http:// dx.doi.org/10.1093/mmcts/mmt021. Perier P. A new paradigm for the repair of posterior leaflet prolapse: respect rather than resect. Oper Tech Thorac Cardiovasc Surg 2005;10:180–93. Lawrie GM, Earle EA, Earle N. Intermediate-term results of a nonresectional dynamic repair technique in 662 patients with mitral valve prolapse and mitral regurgitation. J Thorac Cardiovasc Surg 2011;141:368–76. Asai T, Kinoshita T, Nishimura O, Kambara A, Suzuki T, Matsubayashi K. A novel design of posterior leaflet butterfly resection for mitral valve repair. Innovations (Phila) 2011;6: 54–6. Woo YJ, MacArthur JW. Posterior ventricular anchoring neochordal repair of degenerative mitral regurgitation efficiently remodels and repositions posterior leaflet prolapse. Eur J Cardiothorac Surg 2013;44:485–9. Barlow JB, Pocock WA. Billowing, floppy, prolapsed or flail mitral valves? Am J Cardiol 1985;55:501–2. Carpentier AF, Pellerin M, Fuzellier JF, Relland JY. Extensive calcification of the mitral valve anulus: pathology and surgical management. J Thorac Cardiovasc Surg 1996;111: 718–29. Braunberger E, Deloche A, Berrebi A, Abdallah F, Celestin JA, Meimoun P, et al. Very long-term results (more than 20 years) of valve repair with carpentier's techniques in nonrheumatic mitral valve insufficiency. Circulation 2001;104: 8–11. David TE, Armstrong S, McCrindle BW, Manlhiot C. Late outcomes of mitral valve repair for mitral regurgitation due to degenerative disease. Circulation 2013;127:1485–92. DiBardino DJ, ElBardissi AW, McClure RS, Razo-Vasquez OA, Kelly NE, Cohn LH. Four decades of experience with mitral valve repair: analysis of differential indications, technical evolution, and long-term outcome. J Thorac Cardiovasc Surg 2010;139:76–83. Muneretto C, Bisleri G, Moggi A, Di Bacco L, Tespili M, Repossini A, et al. Treating the patients in the 'grey-zone' with aortic valve disease: a comparison among conventional surgery, sutureless valves and transcatheter aortic valve replacement. Interact Cardiovasc Thorac Surg 2015; 20:90–5. Borger MA, Kaeding AF, Seeburger J, Melnitchouk S, Hoebartner M, Winkfein M, et al. Minimally invasive mitral valve repair in barlow's disease: early and long-term results. J Thorac Cardiovasc Surg 2014;148:1379–85. Galloway AC, Schwartz CF, Ribakove GH, Crooke GA, Gogoladze G, Ursomanno P, et al. A decade of minimally invasive mitral repair: long-term outcomes. Ann Thorac Surg 2009;88:1180–4. David TE, Armstrong S, Ivanov J. Chordal replacement with polytetrafluoroethylene sutures for mitral valve repair: a 25-year experience. J Thorac Cardiovasc Surg 2013;145: 1563–9. Bolling SF, Li S, O'Brien SM, Brennan JM, Prager RL, Gammie JS. Predictors of mitral valve repair: clinical and surgeon factors. Ann Thorac Surg 2010;90:1904–11.
ME
D I C I N E
[30] [31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
] (2015) ]]]–]]]
Badhwar V, George KM. Natural selection and national trends in mitral repair. J Heart Valve Dis 2009;18:355–8. Rosenhek R, Rader F, Klaar U, Gabriel H, Krejc M, Kalbeck D, et al. Outcome of watchful waiting in asymptomatic severe mitral regurgitation. Circulation 2006;113:2238–44. Tribouilloy C, Grigioni F, Avierinos JF, Barbieri A, Rusinaru D, Szymanski C, et al. Survival implication of left ventricular end-systolic diameter in mitral regurgitation due to flail leaflets a long-term follow-up multicenter study. J Am Coll Cardiol 2009;54:1961–8. Bach DS, Awais M, Gurm HS, Kohnstamm S. Failure of guideline adherence for intervention in patients with severe mitral regurgitation. J Am Coll Cardiol 2009;54:860–5. Suri RM, Vanoverschelde JL, Grigioni F, Schaff HV, Tribouilloy C, Avierinos JF, et al. Association between early surgical intervention vs watchful waiting and outcomes for mitral regurgitation due to flail mitral valve leaflets. J Am Med Assoc 2013; 310:609–16. Kang DH, Park SJ, Sun BJ, Cho EJ, Kim DH, Yun SC, et al. Early surgery versus conventional treatment for asymptomatic severe mitral regurgitation: a propensity analysis. J Am Coll Cardiol 2014;63:2398–407. Badhwar V, Peterson ED, Jacobs JP, He X, Brennan JM, O'Brien SM, et al. Longitudinal outcome of isolated mitral repair in older patients: results from 14,604 procedures performed from 1991 to 2007. Ann Thorac Surg 2012;94: 1870–7. Pizarro R, Bazzino OO, Oberti PF, Falconi M, Achilli F, Arias A, et al. Prospective validation of the prognostic usefulness of brain natriuretic peptide in asymptomatic patients with chronic severe mitral regurgitation. J Am Coll Cardiol 2009;54:1099–106. Witkowski TG, Thomas JD, Debonnaire PJ, Delgado V, Hoke U, Ewe SH, et al. Global longitudinal strain predicts left ventricular dysfunction after mitral valve repair. Eur Heart J Cardiovasc Imaging 2013;14:69–76. Pandis D, Sengupta PP, Castillo JG, Caracciolo G, Fischer GW, Narula J, et al. Assessment of longitudinal myocardial mechanics in patients with degenerative mitral valve regurgitation predicts postoperative worsening of left ventricular systolic function. J Am Soc Echocardiogr 2014;27:627–38. Magne J, Lancellotti P, Pierard LA. Exercise-induced changes in degenerative mitral regurgitation. J Am Coll Cardiol 2010;56:300–9. Magne J, Mahjoub H, Dulgheru R, Pibarot P, Pierard LA, Lancellotti P. Left ventricular contractile reserve in asymptomatic primary mitral regurgitation. Eur Heart J 2014;35: 1608–16. Kusunose K, Popovic ZB, Motoki H, Marwick TH. Prognostic significance of exercise-induced right ventricular dysfunction in asymptomatic degenerative mitral regurgitation. Circ Cardiovasc Imaging 2013;6:167–76. Flameng W, Meuris B, Herijgers P, Herregods MC. Durability of mitral valve repair in barlow disease versus fibroelastic deficiency. J Thorac Cardiovasc Surg 2008;135:274–82. Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group a streptococcal diseases. Lancet Infect Dis 2005;5:685–94. Chauvaud S, Fuzellier JF, Berrebi A, Deloche A, Fabiani JN, Carpentier A. Long-term (29 years) results of reconstructive surgery in rheumatic mitral valve insufficiency. Circulation 2001;104:12–5. Kim JB, Kim HJ, Moon DH, Jung SH, Choo SJ, Chung CH, et al. Long-term outcomes after surgery for rheumatic mitral valve disease: valve repair versus mechanical valve replacement. Eur J Cardiothorac Surg 2010;37:1039–46. Chan PG, Hayanga AJ, Wei LM, Badhwar V. Repair of rheumatic mitral stenosis with anterior leaflet augmentation,
T
[48]
[49]
[50]
[51]
[52]
[53]
[54]
[55] [56] [57]
[58]
[59]
[60]
R E N D S I N
C
A R D I O V A S C U L A R
bi-commissural release and oversized annuloplasty: a durable and simplified approach. Multimed Man Cardiothorac Surg 2014;2014, http://dx.doi.org/10.1093/mmcts/mmt020. Yakub MA, Dillon J, Krishna Moorthy PS, Pau KK, Nordin MN. Is rheumatic aetiology a predictor of poor outcome in the current era of mitral valve repair? Contemporary longterm results of mitral valve repair in rheumatic heart disease. Eur J Cardiothorac Surg 2013;44:673–81. Braun J, van de Veire NR, Klautz RJ, Versteegh MI, Holman ER, Westenberg JJ, et al. Restrictive mitral annuloplasty cures ischemic mitral regurgitation and heart failure. Ann Thorac Surg 2008;85:430–6. Magne J, Senechal M, Dumesnil JG, Pibarot P. Ischemic mitral regurgitation: a complex multifaceted disease. Cardiology 2009;112:244–59. Maltais S, Schaff HV, Daly RC, Suri RM, Dearani JA, Sundt TM, et al. Mitral regurgitation surgery in patients with ischemic cardiomyopathy and ischemic mitral regurgitation: factors that influence survival. J Thorac Cardiovasc Surg 2011;142:995–1001. Magne J, Girerd N, Senechal M, Mathieu P, Dagenais F, Dumesnil JG, et al. Mitral repair versus replacement for ischemic mitral regurgitation: comparison of short-term and long-term survival. Circulation 2009;120:104–11. Dayan V, Soca G, Cura L, Mestres CA. Similar survival after mitral valve replacement or repair for ischemic mitral regurgitation: a meta-analysis. Ann Thorac Surg 2014;97: 758–65. Acker MA, Parides MK, Perrault LP, Moskowitz AJ, Gelijns AC, Voisine P, et al. Mitral-valve repair versus replacement for severe ischemic mitral regurgitation. N Engl J Med 2014;370:23–32. Drake DH, Zimmerman KG, Nichols CD. Surgery for severe ischemic mitral regurgitation. N Engl J Med 2014;370:1461. Gorman RC, Gillespie MJ, Gorman JH. Surgery for severe ischemic mitral regurgitation. N Engl J Med 2014;370:1462. Kron IL, Hung J, Overbey JR, Bouchard D, Gelijns AC, Moskowitz AJ, et al. Predicting recurrent mitral regurgitation after mitral valve repair for severe ischemic mitral regurgitation. J Thorac Cardiovasc Surg 2015;149:752–61 [e751]. de Varennes B, Chaturvedi R, Sidhu S, Cote AV, Shan WL, Goyer C, et al. Initial results of posterior leaflet extension for severe type iiib ischemic mitral regurgitation. Circulation 2009;119:2837–43. Rabbah JP, Siefert AW, Bolling SF, Yoganathan AP. Mitral valve annuloplasty and anterior leaflet augmentation for functional ischemic mitral regurgitation: quantitative comparison of coaptation and subvalvular tethering. J Thorac Cardiovasc Surg 2014;148:1688–93. Fattouch K, Castrovinci S, Murana G, Dioguardi P, Guccione F, Nasso G, et al. Papillary muscle relocation and mitral annuloplasty in ischemic mitral valve regurgitation: midterm results. J Thorac Cardiovasc Surg 2014;148:1947–50.
ME
D I C I N E
[61]
[62]
[63]
[64]
[65]
[66]
[67]
[68]
[69]
[70]
[71]
[72]
[73]
[74]
] (2015) ]]]–]]]
9
Hvass U, Joudinaud T. The papillary muscle sling for ischemic mitral regurgitation. J Thorac Cardiovasc Surg 2010;139:418–23. Santana O, Solenkova NV, Pineda AM, Mihos CG, Lamelas J. Minimally invasive papillary muscle sling placement during mitral valve repair in patients with functional mitral regurgitation. J Thorac Cardiovasc Surg 2014;147:496–9. Padala M, Gyoneva LI, Thourani VH, Yoganathan AP. Impact of mitral valve geometry on hemodynamic efficacy of surgical repair in secondary mitral regurgitation. J Heart Valve Dis 2014;23:79–87. Banai S, Jolicoeur EM, Schwartz M, Garceau P, Biner S, Tanguay JF, et al. Tiara: a novel catheter-based mitral valve bioprosthesis: initial experiments and short-term pre-clinical results. J Am Coll Cardiol 2012;60:1430–1. Cheung A, Webb J, Verheye S, Moss R, Boone R, Leipsic J, et al. Short-term results of transapical transcatheter mitral valve implantation for mitral regurgitation. J Am Coll Cardiol 2014;64:1814–9. Bapat V, Buellesfeld L, Peterson MD, Hancock J, Reineke D, Buller C, et al. Transcatheter mitral valve implantation (TMVI) using the edwards fortis device. EuroIntervention 2014;10(Suppl. U):U120–8. Cavalcante JL, Schoenhagen P. Role of cross-sectional imaging for structural heart disease interventions. Cardiol Clin 2013;31:467–78. Feldman T, Young A. Percutaneous approaches to valve repair for mitral regurgitation. J Am Coll Cardiol 2014;63: 2057–68. Wan B, Rahnavardi M, Tian DH, Phan K, Munkholm-Larsen S, Bannon PG, et al. A meta-analysis of MitraClip system versus surgery for treatment of severe mitral regurgitation. Ann Cardiothorac Surg 2013;2:683–92. Bail DH. (Meta)-analysis of safety and efficacy following edge-to-edge mitral valve repair using the MitraClip system. J Interv Cardiol 2015;28:69–75. Glower DD, Kar S, Trento A, Lim DS, Bajwa T, Quesada R, et al. Percutaneous mitral valve repair for mitral regurgitation in high-risk patients: results of the everest ii study. J Am Coll Cardiol 2014;64:172–81. Attizzani GF, Ohno Y, Capodanno D, Cannata S, Dipasqua F, Imme S, et al. Extended use of percutaneous edge-to-edge mitral valve repair beyond everest (endovascular valve edgeto-edge repair) criteria: 30-day and 12-month clinical and echocardiographic outcomes from the grasp (getting reduction of mitral insufficiency by percutaneous clip implantation) registry. JACC Cardiovasc Interv 2015;8:74–82. Estevez-Loureiro R, Franzen O, Winter R, Sondergaard L, Jacobsen P, Cheung G, et al. Echocardiographic and clinical outcomes of central versus noncentral percutaneous edgeto-edge repair of degenerative mitral regurgitation. J Am Coll Cardiol 2013;62:2370–7. Cavalcante JL, Rodriguez LL, Kapadia S, Tuzcu EM, Stewart WJ. Role of echocardiography in percutaneous mitral valve interventions. JACC Cardiovasc Imaging 2012;5:733–46.
E N D S I N
C
A R D I O V A S C U L A R
M
E D I C I N E
] (2015) ]]]–]]]
Available online at www.sciencedirect.com
www.elsevier.com/locate/tcm
A pathoanatomic approach to the management of mitral regurgitation Vinay Badhwarn, Anson J.C. Smith, and João L. Cavalcante The Center for Mitral Valve Disease, Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA
abstra ct Mitral regurgitation remains the most common global valvular heart disease. From otherwise unsuspecting healthy patients without overt symptoms to those with recalcitrant heart failure, mitral valve (MV) disease touches millions of patients per year. While MV prolapse without regurgitation remains benign, once regurgitation begins, quantification of severity is related to prognosis. Understanding the mechanism of regurgitation guides appropriate treatment. Current management guidelines emphasize early therapy after careful assessment of both anatomy and severity of mitral regurgitation. The objective of this review is to provide an update on the treatment of MV disease and to offer additional granularity on pathoanatomic decision making that may aid a more precise application of optimal guideline-directed therapy of primary and secondary mitral regurgitation. Key Words: Mitral valve disease, Mitral regurgitation, Diagnosis, Management, Surgery. & 2015 Elsevier Inc. All rights reserved.
Mitral regurgitation represents the most common valvular disease affecting more than 2 million people in the United States [1]. From otherwise unsuspecting healthy patients without overt symptoms to those with recalcitrant heart failure admissions, MV disease touches millions of patients per year. The structural ideal that “form ever follows function” harmoniously guides the accurate assessment and clinical management of MV disease. Mitral valve prolapse without regurgitation remains benign, but once regurgitation is present the quantification of severity and left ventricular function become important, as they are associated with prognosis. Current management guidelines emphasize early therapy after careful assessment of both anatomy and severity of mitral regurgitation. The objective of this review is to provide an update on the treatment of MV disease and to offer additional granularity on pathoanatomic decision making that may aid a more precise application of optimal guideline-directed therapy.
The increased prevalence of MV disease coupled with several recent advancements in surgical and catheter-based treatment has resulted in a progressive rise in the number of corrective MV interventions performed annually [1,2]. Although there have been exciting developments in catheter-based interventional therapy to minimize mitral regurgitation (MR), these options are currently reserved for frail complex patients with prohibitive surgical risk. The application of a multidisciplinary heart team approach to the diagnosis and management of mitral pathology enhances the evidence-based team approach to direct optimal pathoanatomically appropriate treatment for each patient. We will review the diagnosis and optimal surgical treatment of mitral valve disease as well as note emerging options for interventional management. Together with technical developments in the proficiency and reproducibility of MV repair, the recent progress in preoperative pathoanatomic imaging precision has led to a substantial increase in the number of successful repairs.
The authors have indicated there are no conflicts of interest. n Corresponding author at: Presbyterian University Hospital, 200 Lothrop St, C-700, Pittsburgh, PA. Tel.: þ412 648 6314; fax: þ412 692 2184. E-mail address: [email protected] (V. Badhwar). http://dx.doi.org/10.1016/j.tcm.2015.05.007 1050-1738/& 2015 Elsevier Inc. All rights reserved.
2
T
R E N D S I N
C
A R D I O V A S C U L A R
ME
D I C I N E
] (2015) ]]]–]]]
10,000 9,000 8,000 7,000 6,000 5,000
Mitral Valve Repairs Mitral Valve Repair + CABG Mitral Valve Replacements
4,000 3,000
Mitral Vavle Replacements + CABG Mitral Valve Replacement + AVR
2,000 1,000 0
Fig – Trends of mitral valve surgery in the United States. There has been a doubling of the frequency of mitral valve repair performed over the last 10 years. The rates of isolated mitral replacement have also risen but not to the degree of mitral repair. (Source: The Society of Thoracic Surgeons National Adult Cardiac Surgical Database.) According to the Society of Thoracic Surgeons (STS) National Adult Cardiac Surgery Database, 8662 isolated MV repairs were performed in the last year alone. This represents a 100% increase in just the last decade. In addition, in 2013, there were 4733 MV repairs combined with coronary revascularization, 6554 isolated MV replacements, and 2413 replacements with coronary revascularization (Fig.). The 2014 AHA/ACC Guidelines for the Management of Patients with Valvular Heart Disease recently updated several aspects pertaining to surgical intervention for MV disease [3]. For primary mitral regurgitation (MR), or degenerative disease, MV repair remains the preferred treatment with increasing options for rheumatic disease. Though management of secondary or functional MR remains a challenge, the importance of surgery is emphasized. Surgery remains an integral part of MV disease management and recent improvements in outcomes, access, and surgical techniques have enabled earlier referral for definitive therapy.
Mitral valve pathoanatomy Though MRI and CT are important evolving tools for the assessment of MR and ventricular function, echocardiography remains the primary diagnostic method of choice to aid decision making in mitral valve disease [4–6]. Though much recent focus has been on methods to quantitatively assess MR severity especially in appropriate loading conditions, another key to outcome-directed mitral valve treatment is a detailed pathoanatomic assessment [7–9]. Once the presence and severity of MR have been established (Table 1), clear identification of the etiology and mechanism of MR is of critical importance. This serves to not only aid decision making as to where and when to refer for surgery, but also it provides the primary strategic surgical roadmap toward successful repair. Recent advances in three-dimensional echocardiography now permit clear identification of causative etiology and surgical planning well in advance of entering the operating room. It is therefore of increasing importance that the contemporary MV surgeon possess an in-depth knowledge of MV echocardiographic imaging and
interpretation. Likewise, it is equally important that referring cardiologists understand the various surgical techniques available and how to provide views of the valve to optimally aid in planning therapy. For example, the recent advent of the MitraClip (Abbott Cardiovascular, Abbott Park, IL) that enables the percutaneous delivery of an edge-to-edge mitral leafletsecuring device requires a very specific mitral pathoanatomy to be applicable—most commonly for A2–P2 defect or where there is coaptation loss at the middle of the 2 leaflets. A very well done transthoracic echocardiogram (TTE) can serve to outline most of the mechanism of MV disease. The majority of surgical repair planning can be done with 4 clear views of the mitral valve from conventional twodimensional transesophageal echocardiography (TEE): the mid-esophageal 4-chamber, long-axis 2-chamber, midcommissural 2-chamber, and the basal short-axis view. Though color Doppler mapping setting at a standard Nyquist of 50– 60 cm/sec is helpful to confirm MR mechanism, surgical planning and diagnosis of pathoanatomy is best assessed without color in each of these 4 views. If available, three-dimensional assessment with TEE using surgical “en face” view may be helpful to confirm primary etiology. Three-dimensional TEE can also be helpful in equivocal cases to derive vena contracta area, which is not dependent on any flow or geometric assumptions and has good volumetric correlation with cardiac MRI [4]. It can
Table 1 – Echocardiographic quantitative parameters for severe mitral regurgitation. I. Vena contracta width 40.7 cm II. Systolic flow reversal in the pulmonary veins III. Effective regurgitant orifice area 440 mm2 IV. Regurgitant volume 460 mL V. Regurgitant fraction 450% VI. Prominent flail leaflet or ruptured chordal apparatus Supportive signs: large wall-impinging regurgitant jet (Coanda effect); a large central regurgitant jet (440% of LA), E-wave dominant mitral inflow (E 4 1.2 m/s); severe LA enlargement (especially in setting of normal LV function) Adapted from Grayburn P. Heart 2008;94:376–383.
T
R E N D S I N
C
A R D I O V A S C U L A R
be particularly useful in secondary MR pathology (functional/ ischemic), as the effective regurgitant orifice often extends across the leaflet coaptation and is underestimated by current 2D methods such as the proximal isovelocity surface area. While not critical to primary surgical planning in severe MR, 3D TEE is most useful to finally plan for nuances of repair by focusing attention to potential trouble spots that may not have been clearly detected on 2D imaging such as clefts, commissural pathology, and calcium encroachment of the leaflets that might impact a resection or non-resection repair strategy. High-quality echocardiographic analysis can provide up to 97.8% concordance between preoperative assessment of reparability and successful operative repair [9]. Finally, the use of comprehensive preoperative and postoperative TTE, and intraoperative TEE assessment for all mitral operations is the current standard of care. The contemporary heart team approach to mitral disease involves an in-depth understanding of pathoanatomy to appropriately apply guideline-directed treatment. A collective understanding of terminology is important, as in the commonly used Carpentier classification of mechanism [Type I— normal leaflet motion, annular dilation, and leaflet perforation; Type II—leaflet prolapse, chordal rupture, chordal elongation, papillary muscle rupture, or elongation; Type III— restricted leaflet motion during diastole (IIIa) or systole (IIIb)]. The surgical relevance of leaflet-based primary MR pertains to the sub categorization of degenerative myxomatous disease and fibroelastic deficiency, as well as to the quite different rheumatic pathologies. Secondary or functional MR related to non-leaflet-based etiologies associated to ischemic or dilated myopathies provides an entirely different set of variables when evaluating surgical or interventional options. Surgical approach and timing based on pathoanatomy of primary and secondary MR will be reviewed.
Primary mitral regurgitation Primary MR involves the surgical spectrum from focal mitral prolapse in the setting of an otherwise anatomically normal mitral valve, known as fibroelastic deficiency, to a disease state of myxomatous degeneration manifested by diffuse excess tissue, its zenith being Barlow's disease. The surgical approach to each level of this spectrum is different and pathoanatomically directed. Finally, rheumatic MR is at the opposite end of this spectrum manifested by diffuse leaflet and subvalvular thickening, as well as commissural fusion. The surgical approach is also quite different. While these will be outlined by distinct disease state, it is important to note that in some cases pathoanatomic markers from each of these causes of primary MR may occur simultaneously in 1 patient.
Fibroelastic deficiency First described by Carpentier et al. [10], fibroelastic deficiency is a focal fibrillin deficiency, most commonly affecting the medial posterior (P2) scallop and associated with overall thin leaflet tissue and focally ruptured primary chordae. The remainder of the valve leaflet tissue may be normal or even translucent with relatively normal non-dilated annular dimensions at presentation [11]. Patients are often older and have an abbreviated
ME
D I C I N E
] (2015) ]]]–]]]
3
clinical presentation. This often focal pathology affords a focal surgical solution. Limited triangular resection of the pathology or a polytetrafluoroethylene (PTFE) neochordal support followed by an annuloplasty is most commonly and very successfully applied via conventional sternotomy or minimally invasive and robotic approaches [12].
Myxomatous degeneration The next step on the cascade of degenerative primary MR involves a progression of disease with development of excess leaflet tissue secondary to mucopolysaccharide accumulation in leaflet mucosa. As this degenerative process involves the majority of the posterior leaflet, the P2 scallop can develop excessive tissue and length. The thickness and chordal elongation of the primary chords often result in rupture. Adjacent leaflet components also commonly manifest excess tissue and there is often associated moderate annular dilatation at presentation. The progressed state of myxomatous degeneration involving more than just the P2 scallop of the posterior leaflet is known as forme fruste [13]. These patients often present at younger ages with a longstanding history of MV disease. Anterior leaflet involvement may occur, but this is often focal. This more classic form of mitral prolapse leading to regurgitation requires pathology-directed surgical treatment to often decrease posterior leaflet height and restore leaflet coaptation while preserving leaflet motion (Table 2). Carpentier's classic quadrangular resection with or without a posterior sliding valvuloplasty [13] has long been applied to this pathology. However, depending on the extent of excess tissue, contemporary simplified surgical techniques may involve focal triangular resection with or without ipsilateral posterior chordal transfer [14,15], a non-resection technique using multiple PTFE neochordae only [16,17], modified posterior butterfly-like leaflet resection to decrease posterior leaflet height [18], or even posterior leaflet ventricular anchoring with PTFE [19]. Of course, any combination of these recent techniques could be applied depending on the pathology in order to achieve coaptation restoration and the avoidance of systolic anterior motion (SAM). These surgical techniques may be applied successfully via sternotomy or minimally invasive and robotic approaches depending on surgical experience (Table 3).
Barlow's disease When myxomatous change and excess leaflet tissue is diffuse and extensively involves both leaflets, it is characterized as bileaflet prolapse associated with Barlow's disease [20]. Similar to other forms of myxomatous degeneration, Barlow's patients often present under the age of 60 years with a protracted history of mitral valve prolapse or murmur. Echocardiographically, these often have very large posterior and anterior leaflets with mid-systolic failure of coaptation above the Table 2 – Primary objectives of mitral valve repair. I. Restore leaflet coaptation depth to 45 mm II. Stabilize and remodel the mitral annulus III. Preserve or restore normal leaflet motion IV. No more than mild regurgitation on immediate postoperative echo
4
T
R E N D S I N
C
A R D I O V A S C U L A R
ME
D I C I N E
] (2015) ]]]–]]]
Table 3 – Common contemporary surgical techniques. Primary mitral regurgitation (I) Non-resection techniques using Gore-Texs neochord reconstruction with annuloplasty May be used for focal leaflet flail or bileaflet prolapse May be used for forme fruste diffuse posterior leaflet myxomatous disease May be used for isolated anterior leaflet prolapse
(II) Focal triangular resection with annuloplasty
May be used for focal leaflet flail of the posterior or commissural leaflet
(III) Sliding leaflet valvuloplasty with annuloplasty
May be used for forme fruste diffuse posterior leaflet myxomatous disease May be used in the setting of bileaflet prolapse with excess posterior leaflet May be used in any of the above with significant echocardiographic predictors of systolic anterior motion
Secondary mitral regurgitation
(I) Restrictive remodeling rigid annuloplasty
May be used as primary modality for annular dilatation mechanism May be used in conjunction with secondary or tertiary chordal cutting May be used in conjunction with other adjunctive procedures (i.e., papillary muscle sling)
(II) Chord-sparing mitral valve replacement
May be used as primary modality for annular dilatation with severe leaflet tethering (i.e., 410 mm tenting height)
annular plane, often with multiple MR jets. The excess leaflet scalloping is often associated with pronounced clefts between each posterior scallop. The surgical hallmarks are that of billowing leaflets of excess tissue and a very large mitral annulus often greater than 40 mm at presentation. The surgical strategy may involve many of the techniques outlined earlier but often involves closing clefts, decreasing posterior leaflet height by resection or non-resection techniques, and a large annuloplasty. Patients over the age of 60 years with Barlow's may often have posterior mitral annular calcification (MAC). This may further augment repair complexity, and thus its preoperative identification will assist in navigating this either by resection and leaflet re-implantation [21] or by nonresection methods. Depending on the extent of the mitral pathology, these patients often require surgeons with experience in advanced mitral repair techniques. Results with traditional resection techniques, PTFE neochordal reconstruction, and many contemporary advancements in mitral repair, have consistently been excellent when applied correctly [22–28]. Long-term freedom from mitral regurgitation and reoperation is between 80% and 90%. Clearly, not all patients with severe primary degenerative MR are the same, and thus the value in a preoperative pathoanatomic diagnosis by echocardiography cannot be overstated. When combined with the patient's age and comorbidities, and the center's or surgeon's experience with mitral repair, general knowledge of MR etiology may aid more precise treatment planning. Individual surgeon experience is a known factor for success in mitral repair. There is nearly a 3-fold likelihood of repair when experience is over 100 cases per year compared to 5–10 per year, with a threshold for frequency of success being over 50 cases per year [29,30]. However, these registry estimates lack the pathoanatomic granularity of the mitral disease states going to surgery. As guideline-directed referral for mitral repair is considered for symptomatic patients, the majority of actively practicing cardiac surgeons with good clinical outcomes performing
over 10 repairs per year should be able to successfully repair straight forward posterior leaflet pathology associated with fibroelastic deficiency or uncomplicated focal myxomatous degeneration. However, if the patient is asymptomatic, if the mitral pathoanatomy is more complex, or if a minimally invasive or robotic approach is desired, consideration for experienced surgical referral is warranted to align with the Class IIa recommendation of a heart valve center of excellence with o1% mortality and where a 495% chance at repair may be attainable [3,11].
Timing of surgery for primary degenerative mitral regurgitation As our knowledge gaps on the natural history of uncorrected and corrected severe primary MR have closed in recent years, the concept of “watchful waiting” [31] has ceded to the guideline-supported principles of early surgical referral even in asymptomatic patients [32–35]. This concept has now extended to older individuals who were once relegated to referral only when augmented symptoms existed. Evidence supporting long-term outcome improvement with MV repair has prompted guideline-directed early referral for severe mitral regurgitation to be applied at all age ranges [35,36]. Moreover, regardless of age at the time of successful MV repair, patients can be expected to attain longitudinal survival equivalency to their normal age-matched population [1,23,36].
Outcome predictors following surgery for primary mitral regurgitation For asymptomatic patients with severe MR (Table 1), it may be difficult to know when to refer for surgery, or how to predict the left ventricular (LV) functional response to repair in those with pre-existing LV dysfunction. Brain natriuretic peptide (BNP) levels can serve as a marker of early LV dysfunction. In asymptomatic patients with severe MR, Pizarro et al. [37] found
T
R E N D S I N
C
A R D I O V A S C U L A R
BNP to be a strong independent predictor of late heart failure or death. This early evidence demonstrates that while low BNP levels o105 pg/mL were associated with stable mitral disease, higher levels may be predictive of an unfavorable outcome from severe MR. Thus, BNP may be adjunctive in the assessment of referral timing for asymptomatic patients [8,37]. Recently, speckle tracking two-dimensional strain echocardiography has emerged as a promising technique to detect latent LV contractile impairment occurring early in subendocardial layers. In severe degenerative MR, disproportionately higher LV global longitudinal strain may signify a maladaptive preload-related change that is associated with substantial loss of LV function immediately after MV repair. Preoperative assessment of global longitudinal strain may be potentially useful for optimizing the timing of surgery for degenerative primary MR [38,39]. Dynamic changes in degenerative/primary MR that can be brought on with exercise appear to have an important role [40]. For example, assessment of the MR severity, pulmonary artery systolic arterial pressure, LV contractile reserve with global longitudinal strain [41], and right ventricular function [42] during exercise echocardiography, all appear to have incremental prognostic value over standard baseline assessment. Finally, quality control of intraoperative repair is of critical importance, as any occurrence of more than mild MR is predictive of a poor longitudinal outcome and an increased incidence of reoperation [43]. Thus, if greater than mild MR is identified on the postoperative TEE, immediate correction is recommended.
Rheumatic mitral regurgitation Rheumatic heart disease remains a prevalent problem in non-Western countries resulting from an autoimmunemediated inflammatory process triggered by exposure to group A streptococcus [44]. More common in children, this process attacks the mitral valve most commonly. The inflammatory process affects multiple tissue layers and transforms into fibrosis over time. Valvular fibrosis may be exacerbated by recurrent inflammatory reactions during repeat episodes of rheumatic fever. Fibrosis impacts both the mitral valve tissue as well as the subvalvular apparatus by increased tissue thickness, gradual retraction and deformation, and subsequent predisposition to calcification and stenosis. Though pure regurgitation can be seen, the resulting chronic mitral valve dysfunction commonly manifests as mixed stenosis and regurgitation. Rarely, the inflammatory process itself can be the origin of acute mitral valve regurgitation due to myocarditis and subsequent LV dysfunction or by way of rupture of weakened primary chordae. The common manifestations of late rheumatic MR seen in the United States occur with the pathoanatomic hallmarks of leaflet thickening, fibrotic subvalvular foreshortening, and commissural fusion. If prosthetic-related anticoagulation is questionable and repair is felt to be durable, rheumatic repair consideration is a IIb indication. Surgical correction may require a multitude of techniques that may include leaflet thinning, commissurotomy, chordal resection, PTFE neochords, and annuloplasty. Results of these techniques when performed in experienced centers have been equivalent to prosthetic replacement in terms of durability and outcomes [45,46]. The
ME
D I C I N E
] (2015) ]]]–]]]
5
fibrotic extension of rheumatic pathology is mitral stenosis. In this setting, leaflet augmentation of the posterior leaflet or anterior leaflet when combined with bi-commissural release may provide a non-resection method for a potentially more reproducible repair [47]. When contemporary techniques for rheumatic mitral repair are applied, results in experienced centers can be as good as with degenerative repair [48].
Secondary mitral regurgitation Functional MR secondary to a non-ischemic or ischemic etiology is a disease spectrum that also requires a pathoanatomic approach to discern optimal therapy. In non-ischemic dilated myopathies, the alterations to mitral anatomy stems on a global alteration to ventricular dynamic function with diffuse non-segmental papillary muscle displacement and secondary multi-segment MV leaflet tethering. In functional ischemic MR, segmental alterations in LV function result in post-infarct or post-ischemic event LV remodeling. This in turn leads to initial segmental papillary muscle displacement and regional focal leaflet tethering. This is most commonly associated with posterior papillary muscle fibrosis and displacement. If left untreated or unrecognized, secondary alterations to LV wall stress result in a global alteration in ventricular dynamic function followed eventually by diffuse papillary muscle displacement and multi-segment leaflet tethering. In functional ischemic MR, the results with any form of treatment are inversely proportional with the severity of LV remodeling. As the degree of LV remodeling and MV tethering progresses along this cascade, surgical options to correct MR also must selectively adapt. The broad argument of repair versus replacement cannot be applied for all functional ischemic MR patients, as this is a disease continuum. For many patients early in the spectrum of secondary functional MR, restrictive annuloplasty remains a durable solution with good mid-term outcomes and quality-of-life improvement [49–51]. When surgery for ischemic functional MR is studied as a single-broad pathoanatomic entity, MV repair has nearly half of the operative mortality of MV replacement, but the 5–6-year survival is similar [51–53]. In a recent multicenter randomized trial on MV repair versus replacement for functional ischemic MR, Acker et al. [54] reported similar results. Mitral repair had half of the operative mortality and composite adverse event end points in the first 30 days, but the 1-year outcomes in postoperative survivors were similar. However, notable in this study was a 33% rate of return to moderate-severe MR 1 year following restrictive annuloplasty repair. They concluded that both restrictive annuloplasty and MV replacement were equivalent in the degree of reverse LV remodeling, adverse events, quality of life, and survival at 1 year but advocated that mitral valve replacement is an acceptable treatment option in this population. Though this is one of the rare randomized controlled trials performed in cardiac surgery, this study randomized patients only by MR grade alone instead of pathoanatomy such as degree of tethering, and they defined severe MR as an EROA 4 40 mm2 instead of perhaps the more appropriate, yet still controversial, 420 mm2 for functional MR, as supported in
6
T
R E N D S I N
C
A R D I O V A S C U L A R
the current European guidelines [3,55]. Furthermore, as one interprets this study, it is important to note that if the patients in this trial who had late MR following repair were excluded, those with a successful MV repair had a 22.6% reduction in left ventricular volumes compared to only a 6.8% reduction after MV replacement [56]. This highlights the lack of anatomic granularity in this study and further supports that a more pathoanatomic basis for treatment of this complex disease spectrum is required. To determine the pathoanatomic thresholds for surgical decision making in functional MR, one can examine specific outcome deficiencies with repair. When ventricular dilatation and mitral tethering is severe, outcomes are poor. We know that when the tenting height is greater than 10 mm below the annular plane, inter-papillary muscle distance is greater than 20 mm and the LVEDD is greater than 65 mm, outcomes with restrictive mitral annuloplasty alone are suboptimal and plagued with a higher rate of recurrent MR [55,56]. If annuloplasty is to be attempted, results in non-ischemic patients are superior to those with an ischemic MR etiology, and purely flexible rings or bands are prone to late failure and should not be utilized in functional MR [56]. Therefore, if we follow a pathoanatomic approach to treat functional MR, favorable anatomy for MV repair includes a tenting height of 1 cm or less, a LVEDD of less than 65 mm, and an interpapillary distance of less than 20 mm. In this subgroup, one could expect an acceptable result with reasonable durability and low operative mortality. Of interest, post hoc analysis of the patients who received MV repair in the recent multicenter randomized study [54] revealed 2 important findings: (a) MR recurrence occurred early after surgery (i.e., within 30 days) and mostly moderate in severity and (b) none of the former imaging parameters mentioned before held up in the multivariate model, except for basal aneurysm/dyskinesis. The authors subsequently emphasized that residual tethering post-MV repair is a potential mechanism of MR recurrence in these patients [57]. In this context, we believe that larger studies with detailed phenotyping using multimodality imaging of the pathoanatomic characteristics of these patients will be necessary to better inform best practice for tackling this complex entity. Chord-sparing MV replacement is clearly an acceptable surgical solution for functional MR, particular in the more extreme states of ventricular dilatation and MV leaflet tethering as just outlined. However, there are other contemporary adjunctive solutions that are available to be considered when the pathoanatomy is not within favorable parameters for restrictive annuloplasty alone. These adjunctive valvular or subvalvular procedures to restrictive annuloplasty include anterior or posterior leaflet augmentation [58,59], intra-ventricular papillary muscle surgical relocation [60], and papillary muscle sling implantation [61,62]. These additive mitral repair strategies have shown promising early- and mid-term results and may be integrated into the armamentarium of surgeons experienced in mitral repair. The objective of these supportive procedures in conjunction with annuloplasty is to optimize tethering geometry by altering the chordal stress–strain relationship between the mitral leaflets and ventricle [63]. The clinical decision on how to surgically treat ischemic functional MR is not solved in a debate over broad repair versus
ME
D I C I N E
] (2015) ]]]–]]]
replacement superiority. It is evident from the current literature that both options can be successfully applied. Rather, the future exists in improvements in the granularity of preoperative pathoanatomic identification of those in whom repair would be successful versus those who would benefit from replacement. In equivocal cases, cardiac MRI may become a useful tool to simultaneously assess MV tenting area, LV volumes, sphericity, scar size, location, and papillary muscle involvement. In a similar analogy to the spectrum of primary MR, reduction annuloplasty can be easily standardized and reproduced by any cardiac surgeon performing mitral operations, but complex subvalvular or valvular adjunctive maneuvers are likely best performed by surgeons well versed in these techniques. Coupled with patient factors, preoperative echocardiographic analysis will ultimately identify those patients who can be managed with annuloplasty alone, those who may require reference center MV repair, and those who should be directed toward MV replacement. Particularly in secondary MR, patients at high or prohibitive risk for surgery may be ideally suited for interventional therapy such as the MitraClip. The ongoing trial on Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy (COAPT) for extremely high-surgical-risk patients hopes to determine if there is clinical equipoise in managing these difficult patients.
Interventional mitral therapy When surgery is of prohibitive risk, there are new options for patients on the horizon to manage symptomatic mitral valve disease. There have been several innovations in percutaneous mitral therapy that have brought this into active clinical application. Two new trans-apically implanted catheterbased mitral replacements have seen very early first-in-man clinical experience. Given the anatomical proximity between the mitral and aortic valves, pre-clinical technological developments were necessary to avoid LV outflow tract (LVOT) gradient and/or aortic valve dysfunction [64]. The Tiara pericardial bioprosthetic device (Neovasc Inc., Vancouver, Canada) has a unique D-shaped geometry to fit the asymmetric annulus and 3 anchoring structures into the trigons and posterior shelf of the MV annulus. In pre-clinical and limited published case series, the Tiara device demonstrated good hemodynamics without left ventricular outflow tract obstruction [65]. The Fortis device (Edwards LifeSciences, Irvine, CA) is a similar bovine pericardial bioprosthesis, which has a self-expanding nitinol framed device a slightly higher profile [66]. Use of pre-procedural CT scan for detailed screening of the anatomic suitability is mandatory to avoid potential dynamic LVOT obstruction produced by subvalvular apparatus inclusive of systolic anterior motion of the anterior MV leaflet. At this time, the clinical experience is very limited [66], but ongoing developments will provide further insights into the potential applicability of this device. Coronary sinus devices have been attempted percutaneously with the goal to change the anterior–posterior dimension by displacing the posterior mitral valve leaflet forward, potentially improving leaflet coaptation and reducing mitral regurgitation severity. One of the concerns is the close relationship between the left circumflex artery and the CS and the
T
R E N D S I N
C
A R D I O V A S C U L A R
Table 4 – Anatomic eligibility criteria for MitraClip. Criteria
Optimal valve morphology
Pathoanatomy of regurgitation Leaflet calcification Mitral valve opening area (cm2) Posterior leaflet mobile length (mm) Coaptation depth Leaflet thickness and mobility Myxomatous disease leaflet flail considerations
Central pathology between A2 and P2 segments None Z4 cm2 Z10 mm o11 mm Normal Classical isolated MR prolapsed, flail size o15 mm and flail gap o10 mm
potential for coronary impingement, stenosis/injury. In most patients, the CS courses superiorly to the mitral annulus, whereas the circumflex artery courses between the CS and the mitral annulus in 68–97% of the patients, depending on the coronary dominance. These anatomic considerations have limited the wide applicability of coronary sinus devices. Multi-dimension CT may provide useful information in eligibility and selection of potential candidates for percutaneous mitral annuloplasty via the coronary sinus approach [67]. However, the one with largest experience to date (nearly 17,000 patients worldwide as of the beginning of 2015) and most commonly used interventional approach to MR remains the MitraClip system, which is peripherally inserted via the femoral vein and delivered by trans-septal approach [68]. The MitraClip system has demonstrated adequate procedural safety with good short- and intermediate-term success and low mortality [69,70]. Favorable results from the EVEREST II trial in USA have led to the device approval by the FDA in 2014 for patients with primary/degenerative MR of prohibitive surgical risk where a heart team approach including a surgeon expert has deemed the patient pathoanatomically suitable [71]. While the ideal anatomy for the MitraClip involves the malcoaptation of the A2–P2 segments of the leaflets, there is emerging European experience with successful treatment of more medial or lateral defects in select cases [72,73]. The COAPT clinical trial, designed as a noninferiority study to medical management, hopes to determine the ideal patient selection in inoperable cases of secondary MR. Strict selectionbased anatomical criteria and thorough intra-procedural guidance with transesophageal echocardiography are essential for the successful delivery of this new therapy (Table 4) [74].
Summary Recent technical advancements in the surgical management of mitral valve disease endeavor to more reproducibly adhere to the principles of restoration or preservation of leaflet motion, annular integrity, and coaptation depth. Together with improvements in medical management, valve imaging, and a growing trend toward more durable and minimally invasive repairs, the paradigm of how we manage mitral valve disease is substantively evolving. The recent 2014 AHA/ACC Valvular Management guidelines [3] echo these developments. The prevailing trend
ME
D I C I N E
] (2015) ]]]–]]]
7
toward MV repair as the standard of care for primary severe MR has changed mitral disease from a condition in which we respond to late complications such as atrial fibrillation, pulmonary hypertension, and ventricular remodeling, into one in which we proactively treat prior to the natural development of these sequelae. It is clear that earlier surgical intervention for severe MR, even in asymptomatic patients, provides longitudinal quality of life and survival benefits. With increasing surgical education and proliferation of MV repair expertise, patients will continue to benefit from more access to centers of excellence. Access to advanced surgical or interventional therapies should be in the form of a multidisciplinary heart team environment with specialized surgeons, interventionalists, and imagers focused on all aspects of mitral valve disease. Both cardiology and cardiothoracic surgical communities must continue to stringently investigate rapidly developing techniques as a unified consortium as we together close the knowledge gap in mitral disease. This form of partnership will assure the safe development of new therapeutic options for mitral pathologies while supporting wider patient access focused on maintaining the highest standards-of-quality outcomes.
refere nces
[1]
Enriquez-Sarano M, Akins CW, Vahanian A. Mitral regurgitation. Lancet 2009;373:1382–94. [2] Gammie JS, Sheng S, Griffith BP, Peterson ED, Rankin JS, O'Brien SM, et al. Trends in mitral valve surgery in the united states: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Ann Thorac Surg 2009;87: 1431–7. [3] Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/ American Heart Association task force on practice guidelines. J Am Coll Cardiol 2014;63:2438–88. [4] Thavendiranathan P, Phelan D, Thomas JD, Flamm SD, Marwick TH. Quantitative assessment of mitral regurgitation: validation of new methods. J Am Coll Cardiol 2012;60: 1470–83. [5] Grayburn PA, Weissman NJ, Zamorano JL. Quantitation of mitral regurgitation. Circulation 2012;126:2005–17. [6] Monin JL, Dehant P, Roiron C, Monchi M, Tabet JY, Clerc P, et al. Functional assessment of mitral regurgitation by transthoracic echocardiography using standardized imaging planes diagnostic accuracy and outcome implications. J Am Coll Cardiol 2005;46:302–9. [7] Pepi M, Tamborini G, Maltagliati A, Galli CA, Sisillo E, Salvi L, et al. Head-to-head comparison of two- and threedimensional transthoracic and transesophageal echocardiography in the localization of mitral valve prolapse. J Am Coll Cardiol 2006;48:2524–30. [8] Bergler-Klein J. Global longitudinal strain for predicting outcome after mitral repair or cardiac surgery: here to stay? Eur Heart J Cardiovasc Imaging 2013;14:12–4. [9] Drake DH, Zimmerman KG, Hepner AM, Nichols CD. Echoguided mitral repair. Circ Cardiovasc Imaging 2014;7:132–41. [10] Carpentier A, Lacour-Gayet F, Camilleri J, Dubost C. Fibroelastic dysplasia of the mitral valve: an anatomical and clinical entity. Circulation 1980;62:207. [11] Adams DH, Rosenhek R, Falk V. Degenerative mitral valve regurgitation: best practice revolution. Eur Heart J 2010;31: 1958–66.
8
[12]
[13]
[14] [15]
[16]
[17]
[18]
[19]
[20] [21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
T
R E N D S I N
C
A R D I O V A S C U L A R
Suri RM, Schaff HV, Meyer SR, Hargrove WC. Thoracoscopic versus open mitral valve repair: a propensity score analysis of early outcomes. Ann Thorac Surg 2009;88:1185–90. Carpentier A, Chauvaud S, Fabiani JN, Deloche A, Relland J, Lessana A, et al. Reconstructive surgery of mitral valve incompetence: ten-year appraisal. J Thorac Cardiovasc Surg 1980;79:338–48. Glower DD. Surgical approaches to mitral regurgitation. J Am Coll Cardiol 2012;60:1315–22. Schaheen LW, Hayanga AJ, Wei LM, Badhwar V. Chordal transfer for repair of anterior leaflet flail: a reproducible option. Multimed Man Cardiothorac Surg 2014;2014, http:// dx.doi.org/10.1093/mmcts/mmt021. Perier P. A new paradigm for the repair of posterior leaflet prolapse: respect rather than resect. Oper Tech Thorac Cardiovasc Surg 2005;10:180–93. Lawrie GM, Earle EA, Earle N. Intermediate-term results of a nonresectional dynamic repair technique in 662 patients with mitral valve prolapse and mitral regurgitation. J Thorac Cardiovasc Surg 2011;141:368–76. Asai T, Kinoshita T, Nishimura O, Kambara A, Suzuki T, Matsubayashi K. A novel design of posterior leaflet butterfly resection for mitral valve repair. Innovations (Phila) 2011;6: 54–6. Woo YJ, MacArthur JW. Posterior ventricular anchoring neochordal repair of degenerative mitral regurgitation efficiently remodels and repositions posterior leaflet prolapse. Eur J Cardiothorac Surg 2013;44:485–9. Barlow JB, Pocock WA. Billowing, floppy, prolapsed or flail mitral valves? Am J Cardiol 1985;55:501–2. Carpentier AF, Pellerin M, Fuzellier JF, Relland JY. Extensive calcification of the mitral valve anulus: pathology and surgical management. J Thorac Cardiovasc Surg 1996;111: 718–29. Braunberger E, Deloche A, Berrebi A, Abdallah F, Celestin JA, Meimoun P, et al. Very long-term results (more than 20 years) of valve repair with carpentier's techniques in nonrheumatic mitral valve insufficiency. Circulation 2001;104: 8–11. David TE, Armstrong S, McCrindle BW, Manlhiot C. Late outcomes of mitral valve repair for mitral regurgitation due to degenerative disease. Circulation 2013;127:1485–92. DiBardino DJ, ElBardissi AW, McClure RS, Razo-Vasquez OA, Kelly NE, Cohn LH. Four decades of experience with mitral valve repair: analysis of differential indications, technical evolution, and long-term outcome. J Thorac Cardiovasc Surg 2010;139:76–83. Muneretto C, Bisleri G, Moggi A, Di Bacco L, Tespili M, Repossini A, et al. Treating the patients in the 'grey-zone' with aortic valve disease: a comparison among conventional surgery, sutureless valves and transcatheter aortic valve replacement. Interact Cardiovasc Thorac Surg 2015; 20:90–5. Borger MA, Kaeding AF, Seeburger J, Melnitchouk S, Hoebartner M, Winkfein M, et al. Minimally invasive mitral valve repair in barlow's disease: early and long-term results. J Thorac Cardiovasc Surg 2014;148:1379–85. Galloway AC, Schwartz CF, Ribakove GH, Crooke GA, Gogoladze G, Ursomanno P, et al. A decade of minimally invasive mitral repair: long-term outcomes. Ann Thorac Surg 2009;88:1180–4. David TE, Armstrong S, Ivanov J. Chordal replacement with polytetrafluoroethylene sutures for mitral valve repair: a 25-year experience. J Thorac Cardiovasc Surg 2013;145: 1563–9. Bolling SF, Li S, O'Brien SM, Brennan JM, Prager RL, Gammie JS. Predictors of mitral valve repair: clinical and surgeon factors. Ann Thorac Surg 2010;90:1904–11.
ME
D I C I N E
[30] [31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
] (2015) ]]]–]]]
Badhwar V, George KM. Natural selection and national trends in mitral repair. J Heart Valve Dis 2009;18:355–8. Rosenhek R, Rader F, Klaar U, Gabriel H, Krejc M, Kalbeck D, et al. Outcome of watchful waiting in asymptomatic severe mitral regurgitation. Circulation 2006;113:2238–44. Tribouilloy C, Grigioni F, Avierinos JF, Barbieri A, Rusinaru D, Szymanski C, et al. Survival implication of left ventricular end-systolic diameter in mitral regurgitation due to flail leaflets a long-term follow-up multicenter study. J Am Coll Cardiol 2009;54:1961–8. Bach DS, Awais M, Gurm HS, Kohnstamm S. Failure of guideline adherence for intervention in patients with severe mitral regurgitation. J Am Coll Cardiol 2009;54:860–5. Suri RM, Vanoverschelde JL, Grigioni F, Schaff HV, Tribouilloy C, Avierinos JF, et al. Association between early surgical intervention vs watchful waiting and outcomes for mitral regurgitation due to flail mitral valve leaflets. J Am Med Assoc 2013; 310:609–16. Kang DH, Park SJ, Sun BJ, Cho EJ, Kim DH, Yun SC, et al. Early surgery versus conventional treatment for asymptomatic severe mitral regurgitation: a propensity analysis. J Am Coll Cardiol 2014;63:2398–407. Badhwar V, Peterson ED, Jacobs JP, He X, Brennan JM, O'Brien SM, et al. Longitudinal outcome of isolated mitral repair in older patients: results from 14,604 procedures performed from 1991 to 2007. Ann Thorac Surg 2012;94: 1870–7. Pizarro R, Bazzino OO, Oberti PF, Falconi M, Achilli F, Arias A, et al. Prospective validation of the prognostic usefulness of brain natriuretic peptide in asymptomatic patients with chronic severe mitral regurgitation. J Am Coll Cardiol 2009;54:1099–106. Witkowski TG, Thomas JD, Debonnaire PJ, Delgado V, Hoke U, Ewe SH, et al. Global longitudinal strain predicts left ventricular dysfunction after mitral valve repair. Eur Heart J Cardiovasc Imaging 2013;14:69–76. Pandis D, Sengupta PP, Castillo JG, Caracciolo G, Fischer GW, Narula J, et al. Assessment of longitudinal myocardial mechanics in patients with degenerative mitral valve regurgitation predicts postoperative worsening of left ventricular systolic function. J Am Soc Echocardiogr 2014;27:627–38. Magne J, Lancellotti P, Pierard LA. Exercise-induced changes in degenerative mitral regurgitation. J Am Coll Cardiol 2010;56:300–9. Magne J, Mahjoub H, Dulgheru R, Pibarot P, Pierard LA, Lancellotti P. Left ventricular contractile reserve in asymptomatic primary mitral regurgitation. Eur Heart J 2014;35: 1608–16. Kusunose K, Popovic ZB, Motoki H, Marwick TH. Prognostic significance of exercise-induced right ventricular dysfunction in asymptomatic degenerative mitral regurgitation. Circ Cardiovasc Imaging 2013;6:167–76. Flameng W, Meuris B, Herijgers P, Herregods MC. Durability of mitral valve repair in barlow disease versus fibroelastic deficiency. J Thorac Cardiovasc Surg 2008;135:274–82. Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group a streptococcal diseases. Lancet Infect Dis 2005;5:685–94. Chauvaud S, Fuzellier JF, Berrebi A, Deloche A, Fabiani JN, Carpentier A. Long-term (29 years) results of reconstructive surgery in rheumatic mitral valve insufficiency. Circulation 2001;104:12–5. Kim JB, Kim HJ, Moon DH, Jung SH, Choo SJ, Chung CH, et al. Long-term outcomes after surgery for rheumatic mitral valve disease: valve repair versus mechanical valve replacement. Eur J Cardiothorac Surg 2010;37:1039–46. Chan PG, Hayanga AJ, Wei LM, Badhwar V. Repair of rheumatic mitral stenosis with anterior leaflet augmentation,
T
[48]
[49]
[50]
[51]
[52]
[53]
[54]
[55] [56] [57]
[58]
[59]
[60]
R E N D S I N
C
A R D I O V A S C U L A R
bi-commissural release and oversized annuloplasty: a durable and simplified approach. Multimed Man Cardiothorac Surg 2014;2014, http://dx.doi.org/10.1093/mmcts/mmt020. Yakub MA, Dillon J, Krishna Moorthy PS, Pau KK, Nordin MN. Is rheumatic aetiology a predictor of poor outcome in the current era of mitral valve repair? Contemporary longterm results of mitral valve repair in rheumatic heart disease. Eur J Cardiothorac Surg 2013;44:673–81. Braun J, van de Veire NR, Klautz RJ, Versteegh MI, Holman ER, Westenberg JJ, et al. Restrictive mitral annuloplasty cures ischemic mitral regurgitation and heart failure. Ann Thorac Surg 2008;85:430–6. Magne J, Senechal M, Dumesnil JG, Pibarot P. Ischemic mitral regurgitation: a complex multifaceted disease. Cardiology 2009;112:244–59. Maltais S, Schaff HV, Daly RC, Suri RM, Dearani JA, Sundt TM, et al. Mitral regurgitation surgery in patients with ischemic cardiomyopathy and ischemic mitral regurgitation: factors that influence survival. J Thorac Cardiovasc Surg 2011;142:995–1001. Magne J, Girerd N, Senechal M, Mathieu P, Dagenais F, Dumesnil JG, et al. Mitral repair versus replacement for ischemic mitral regurgitation: comparison of short-term and long-term survival. Circulation 2009;120:104–11. Dayan V, Soca G, Cura L, Mestres CA. Similar survival after mitral valve replacement or repair for ischemic mitral regurgitation: a meta-analysis. Ann Thorac Surg 2014;97: 758–65. Acker MA, Parides MK, Perrault LP, Moskowitz AJ, Gelijns AC, Voisine P, et al. Mitral-valve repair versus replacement for severe ischemic mitral regurgitation. N Engl J Med 2014;370:23–32. Drake DH, Zimmerman KG, Nichols CD. Surgery for severe ischemic mitral regurgitation. N Engl J Med 2014;370:1461. Gorman RC, Gillespie MJ, Gorman JH. Surgery for severe ischemic mitral regurgitation. N Engl J Med 2014;370:1462. Kron IL, Hung J, Overbey JR, Bouchard D, Gelijns AC, Moskowitz AJ, et al. Predicting recurrent mitral regurgitation after mitral valve repair for severe ischemic mitral regurgitation. J Thorac Cardiovasc Surg 2015;149:752–61 [e751]. de Varennes B, Chaturvedi R, Sidhu S, Cote AV, Shan WL, Goyer C, et al. Initial results of posterior leaflet extension for severe type iiib ischemic mitral regurgitation. Circulation 2009;119:2837–43. Rabbah JP, Siefert AW, Bolling SF, Yoganathan AP. Mitral valve annuloplasty and anterior leaflet augmentation for functional ischemic mitral regurgitation: quantitative comparison of coaptation and subvalvular tethering. J Thorac Cardiovasc Surg 2014;148:1688–93. Fattouch K, Castrovinci S, Murana G, Dioguardi P, Guccione F, Nasso G, et al. Papillary muscle relocation and mitral annuloplasty in ischemic mitral valve regurgitation: midterm results. J Thorac Cardiovasc Surg 2014;148:1947–50.
ME
D I C I N E
[61]
[62]
[63]
[64]
[65]
[66]
[67]
[68]
[69]
[70]
[71]
[72]
[73]
[74]
] (2015) ]]]–]]]
9
Hvass U, Joudinaud T. The papillary muscle sling for ischemic mitral regurgitation. J Thorac Cardiovasc Surg 2010;139:418–23. Santana O, Solenkova NV, Pineda AM, Mihos CG, Lamelas J. Minimally invasive papillary muscle sling placement during mitral valve repair in patients with functional mitral regurgitation. J Thorac Cardiovasc Surg 2014;147:496–9. Padala M, Gyoneva LI, Thourani VH, Yoganathan AP. Impact of mitral valve geometry on hemodynamic efficacy of surgical repair in secondary mitral regurgitation. J Heart Valve Dis 2014;23:79–87. Banai S, Jolicoeur EM, Schwartz M, Garceau P, Biner S, Tanguay JF, et al. Tiara: a novel catheter-based mitral valve bioprosthesis: initial experiments and short-term pre-clinical results. J Am Coll Cardiol 2012;60:1430–1. Cheung A, Webb J, Verheye S, Moss R, Boone R, Leipsic J, et al. Short-term results of transapical transcatheter mitral valve implantation for mitral regurgitation. J Am Coll Cardiol 2014;64:1814–9. Bapat V, Buellesfeld L, Peterson MD, Hancock J, Reineke D, Buller C, et al. Transcatheter mitral valve implantation (TMVI) using the edwards fortis device. EuroIntervention 2014;10(Suppl. U):U120–8. Cavalcante JL, Schoenhagen P. Role of cross-sectional imaging for structural heart disease interventions. Cardiol Clin 2013;31:467–78. Feldman T, Young A. Percutaneous approaches to valve repair for mitral regurgitation. J Am Coll Cardiol 2014;63: 2057–68. Wan B, Rahnavardi M, Tian DH, Phan K, Munkholm-Larsen S, Bannon PG, et al. A meta-analysis of MitraClip system versus surgery for treatment of severe mitral regurgitation. Ann Cardiothorac Surg 2013;2:683–92. Bail DH. (Meta)-analysis of safety and efficacy following edge-to-edge mitral valve repair using the MitraClip system. J Interv Cardiol 2015;28:69–75. Glower DD, Kar S, Trento A, Lim DS, Bajwa T, Quesada R, et al. Percutaneous mitral valve repair for mitral regurgitation in high-risk patients: results of the everest ii study. J Am Coll Cardiol 2014;64:172–81. Attizzani GF, Ohno Y, Capodanno D, Cannata S, Dipasqua F, Imme S, et al. Extended use of percutaneous edge-to-edge mitral valve repair beyond everest (endovascular valve edgeto-edge repair) criteria: 30-day and 12-month clinical and echocardiographic outcomes from the grasp (getting reduction of mitral insufficiency by percutaneous clip implantation) registry. JACC Cardiovasc Interv 2015;8:74–82. Estevez-Loureiro R, Franzen O, Winter R, Sondergaard L, Jacobsen P, Cheung G, et al. Echocardiographic and clinical outcomes of central versus noncentral percutaneous edgeto-edge repair of degenerative mitral regurgitation. J Am Coll Cardiol 2013;62:2370–7. Cavalcante JL, Rodriguez LL, Kapadia S, Tuzcu EM, Stewart WJ. Role of echocardiography in percutaneous mitral valve interventions. JACC Cardiovasc Imaging 2012;5:733–46.