Percutaneous annuloplasty approaches target the mitral annulus either directly at the level of the annulus or indirectly via the coronary sinus. Access to the annulus can be obtained either through transseptal puncture or retrogradely via the aortic valve and the left ventricle (LV). These devices are implanted into the annulus to directly reduce its circumference.

The Cardioband system (Valtech, Israel) combines an annuloplasty implant with a transfemoral venous delivery system, by utilizing transseptal percutaneous placement of a series of small corkscrew anchors on the atrial side of the left atrium under transesophageal echocardiographic guidance. The anchors are connected by a Dacron sleeve that can be subsequently tensioned reducing the mitral annular circumference. Early results in humans, in a European CE Mark trial, showed a significant reduction of MR and an improvement in terms of functional class at the 6-month follow-up, leading to recent CE Mark approval.

The key aspect of this technology is careful preprocedural planning requiring computed tomography (CT) to assess the size of the annulus, the appropriate fluoroscopic projections, and the location of the transseptal puncture.

The anatomic relationship of the coronary sinus (CS) with the mitral annulus has stimulated much interest in using the CS to reduce mitral annular dimensions. The CS is located in the posterior portion of the coronary sulcus on the diaphragmatic or posterior surface of the heart and in many cases lies in close proximity to the mitral annulus.

The Carillon device (Cardiac Dimensions, Kirkland, Washington DC, USA) is a self-expandable nitinol device with semihelical distal and proximal anchors connected by a nitinol bridge that is placed in the coronary sinus via a jugular venous approach. Tension generated by this system results in cinching of posterior mitral annulus pushing it anteriorly.

The Carillon Mitral Annuloplasty Device European Union Study (AMADEUS) was the first investigation of a percutaneous coronary sinus-based intervention to reduce FMR [7]. This study enrolled 48 symptomatic patients with dilated cardiomyopathy, at least moderate FMR and a LVEF <40 %. Of the 48 patients enrolled in the trial, 30 received the Carillon device. Eighteen patients did not receive a device because of access issues, insufficient acute MR reduction, or coronary artery compromise. The major adverse event rate was 13 % at 30 days. At 6 months, the degree of MR reduction among five different quantitative echocardiographic measures ranged from 22 to 32 %. Despite improvement of quality of life and functional indices, there was no significant change in left ventricular remodeling at 6 months. The device has been subsequently improved to increase resistance and reduce the risk of fracture. The device efficacy was tested in the Transcatheter Implantation of Carillon Mitral Annuloplasty Device (TITAN) trial [8], which included 53 patients, 36 of whom received the device. The TITAN trial revealed a mortality rate of 1.9 % at 30 days after the procedure without other major complications. Successful device therapy showed significant reduction in MR grade, favorable LV remodeling, and improved quality of life when compared with the control group of subjects who did not receive implants [8].

The edge-to-edge repair has been used as a surgical technique for the treatment of MR since the early 1990s pioneered by Alfieri [12]. This technique involves suturing a portion of the anterior leaflet to the corresponding portion of the posterior leaflet, creating a point of permanent approximation of the two leaflets and resulting in a double orifice. The percutaneous technique is performed using the MitraClip system (Abbott Vascular, Abbott Park, IL, USA), which consists of applying a clip at the site of MR, thereby reproducing the edge-to-edge surgical technique. The MitraClip is a transvenous procedure performed under general anesthesia with TEE guidance. Following transseptal puncture, the clip is advanced via the guiding catheter into the left atrium and steered toward the mitral leaflets. Using TEE guidance, the site of MR is identified, and the clip is placed at the area of the regurgitant jet. Once appropriately positioned, the clip is closed and the effect on MR is assessed. The clip can be opened and repositioned as required to achieve optimal MR reduction. Closure of the clip results in leaflet coaptation and the formation of a bridge between the anterior and posterior leaflets.

Synthetic chord technology, designed mainly for degenerative MR (with posterior leaflet prolapse), can be implanted via a transapical or transseptal approach, and they are anchored between the left ventricular myocardium and the leaflet. In appropriate patients, MR can be reduced or abolished by adjusting the length of the chord. At present, NeoChord DS1000 (NeoChord, Inc, Minnetonka, MN) is the only CE marked chordal implantation system. The device is a transapically inserted tool that can capture a flail leaflet segment, pierce it with a needle, and attach a standard polytetrafluoroethylene artificial chord which is then anchored to the apical entry site with a pledgeted suture. The available clinical evidence is comprised of the Transapical Artificial Chordae Tendineae (TACT) trial [13] by Seeburger et al. which enrolled 30 patients at seven centers in Europe. Among the initial population, acute procedural success (placement of ≥1 NeoChord and reduction of MR from 3+/4+ to ≤2+) was achieved in 26 (86.7 %) patients. Four patients did not receive repair with the device at the discretion of the surgeon. Major adverse events included one death and one minor stroke. At 30 days, 17 patients had an MR grade 2+ or greater.

Organic or degenerative disease is defined as a spectrum of conditions in which infiltrative or dysplastic tissue changes cause elongation or rupture of the MV chordae, resulting in leaflet prolapse and usually associated with annular dilation [14]. At one end of the spectrum of organic mitral disease is fibroelastic deficiency, characterized by insufficient tissue in a normal-sized valve leaflets which are thinned and almost transparent and chordae which are flimsy and thin. MR is most frequently caused by rupture of a single chord associated with a single prolapsing segment, usually P2, resulting in Carpentier’s type II leaflet dysfunction. The prolapsing segment may become distended and thickened by a localized myxomatous process in the chronic condition.

At the opposite end of the spectrum of degenerative MR is Barlow’s disease, characterized by marked excess tissue involving multiple leaflet segments in an otherwise large valve. Leaflet tissue is thickened and redundant, with thick, elongated, mesh-like chordae which may or may not be ruptured [14].

MR severity depends on the number of prolapsing leaflet segments (Carpentier’s type II). Finally, the pathophysiology of MR differs depending on whether valve damage is acute or the result of a chronic process. The causes that generally elicit primary acute MR are spontaneous rupture of the chordae tendineae, acute endocarditis, or chest trauma [15]. In the acute stage, which usually occurs with a spontaneous chordae tendineae or papillary muscle rupture secondary to myocardial infarction, a sudden volume overload occurs on an unprepared LV and left atrium. The volume overload on the LV increases left ventricular stroke work. Increased left ventricular filling pressures, combined with the transfer of blood from the LV to the left atrium during systole, result in elevated left atrial pressures. This increased pressure is transmitted to the lungs resulting in acute pulmonary edema and dyspnea. In the case of chronic MR, there is plenty of time for the left atrium and LV to make compensatory changes allowing for increased atrial and pulmonary vein compliance.

Therefore, patients do not usually report the symptoms of pulmonary edema for many years. The chronic compensated phase results in eccentric left ventricular hypertrophy. The combination of increased preload and hypertrophy produces increased end-diastolic volumes, which, over time, result in left ventricular muscle dysfunction. This muscle dysfunction impairs the emptying of the ventricle during systole. The regurgitant volume and left atrial pressures increase, leading to pulmonary congestion, ultimately leading to pulmonary edema and, if left untreated, cardiogenic shock.

Traditionally functional MR has been described as a structurally normal MV with impaired function due to ventricular dilation and dysfunction. However, new insights in myocardial adaptation have also demonstrated abnormalities in the mitral leaflets. Indeed FMR is not simply a disease of ventricular dysfunction and might be better understood in terms of ventricular, subvalvular, and valvular interaction and adaptation [16, 17]. LV dilation due to ischemic or nonischemic cardiomyopathy secondarily impairs leaflet coaptation of a structurally normal MV, resulting in secondary MR. Specifically, LV dysfunction and remodeling lead to apical and lateral papillary muscle displacement, resulting in leaflet tethering, dilation and flattening of the mitral annulus, and reduced valve closing forces. Because these changes are dependent on loading conditions and the phase of the cardiac cycle, secondary MR is dynamic in nature [18]. The normal saddle shape of the annulus is important for maintaining normal leaflet stress. Loss of this shape and annular flattening with LV remodeling result in increased leaflet stress with secondary MR. In addition, LV systolic dysfunction reduces the strength of MV closing, which opposes the leaflet tethering forces created by papillary muscle displacement. These pathological changes culminate in failure of leaflet coaptation and decreased valvular closing forces due to LV dysfunction, resulting in MR [19]. MR can be further classified as either ischemic or nonischemic. In ischemic MR (the more frequent etiology), LV remodeling after myocardial infarction (MI) results in papillary muscle displacement, causing systolic tenting of the MV. Global left ventricular ejection fraction (LVEF) does not have to be reduced; regional wall motion abnormalities with remodeling may result in sufficient MV tethering to cause severe MR, despite preserved LVEF [20]. Symmetric or asymmetric leaflet tethering may occur. Symmetric tethering is associated with substantial systolic dysfunction, global remodeling, and increased LV sphericity with a central regurgitant jet. Asymmetric tethering most frequently results from localized remodeling affecting the posterior papillary muscle, with posterior tenting of both leaflets (most pronounced at the medial or P3 portion of the posterior leaflet) causing a posteriorly directed asymmetric regurgitant jet (Carpentier’s type IIIB). Mitral annular dilation typically occurs late in the pathophysiology of secondary MR and is often asymmetric, with greater involvement of the posterior annulus. Papillary muscle infarction is rarely the cause of secondary MR [21]. Nonischemic MR, most commonly due to long-standing hypertension or idiopathic dilated cardiomyopathy, is characterized by global LV dilation with increased sphericity and (typically) a centrally located regurgitant jet. Symmetric mitral annular dilation is greatest in the septal-lateral direction and correlates with the severity of LV dysfunction [22].

In chronic primary MR, pathology of at least one of the components of the MV (leaflets, chordae tendineae, papillary muscles, annulus) causes valve incompetence with systolic regurgitation of blood from the LV to the left atrium. The anatomic substrate for degenerative MR spans the spectrum from diffuse myxomatous changes (Barlow’s disease) to localized abnormalities associated with fibroelastic deficiency. The myxomatous degeneration of the MV is characterized by thickened (>5 mm), redundant leaflets and chordae tendineae, with bulging of the valve leaflets into the left atrium during systole.

According to the ACC/AHA valvular heart disease guidelines [3], primary MR is classified into one of the four categories shown in Table 9.1.

In regard to interventions for primary MR, the ACC/AHA guidelines recommend MV surgery for symptomatic patients with chronic severe primary MR (stage D) and LVEF >30 % and for asymptomatic patients with chronic severe primary MR and LV dysfunction (LVEF 30–60 % and/or LVESD ≥40 mm, stage C2) (class of recommendation, I; level of evidence, B).

Conversely, the guidelines suggest transcatheter MV repair may be considered for severely symptomatic patients (NYHA class III–IV) with chronic severe primary MR (stage D) who have favorable anatomy for the repair procedure and a reasonable life expectancy but who have a prohibitive surgical risk because of severe comorbidities and remain severely symptomatic despite guideline-directed medical therapy (GDMT) for HF (class of recommendation, IIb; level of evidence, B).