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Page 2 of 12 Masiero et al. Mini-invasive Surg 2020;4:71 I http://dx.doi.org/10.20517/2574-1225.2020.56

INTRODUCTION
Secondary mitral valve regurgitation (MR) is a heterogeneous entity afflicting patients with heart failure
(HF) and is almost twice as common as the degenerative type. It occurs in up to 60% of patients after a
[1]
myocardial infarction and is present in more than half of patients with dilated cardiomyopathy . Despite
its high prevalence, the optimal therapeutic apprsoach remains a matter of debate, with a disappointingly
low level of evidence for guideline recommendations. The aim of this review is to portray the percutaneous
treatment of functional MR through transcatheter “edge-to-edge” leaflet repair, from available evidence to
technical practice.

ETIOLOGY AND TREATMENT OF SECONDARY MR
Functional MR results from an imbalance between closing forces and tethering or pushing strengths
acting on the valve in the absence of structural alterations of mitral valve (MV) apparatus. It may occur in
patients with heart failure both with reduced ejection fraction (HFrEF) or with preserved ejection fraction
[2]
(HFpEF) . In the former setting, the underlying ischemic or non-ischemic triggers determine an eccentric
left ventricle (LV) remodeling, either global or regional, with papillary muscle displacement resulting in
enhanced tethering forces on the leaflets; on the other hand, ventricular dysfunction and annular dilatation
determine a reduction in closing forces. The resulting secondary MR turns in chronic LV volume overload,
thus inducing further remodeling and progression of the disease. In time, an LV diastolic dysfunction
occurs, causing an increase in left atrial (LA) pressure and subsequent LA remodeling and enlargement with
further annular dilatation, thus contributing to MV tenting [Figure 1]. More than 20% of patients with
[2,3]
[4]
HFrEF have severe MR, with comparable rates between ischemic and non-ischemic etiologies . Functional
MR is also found in a significant proportion of patients with HFpEF but still little is known about its
pathogenesis, clinical implications, and prognostic importance. Clinical conditions frequently associated
in this setting include atrial fibrillation, severe aortic stenosis, diabetes mellitus and myocardial ischemic
disease. Systolic MV tenting is supposedly due to LV diastolic disfunction causing increased LV and LA
filling pressure, which in turn determines LA enlargement, annular dilatation, and leaflets malcoaptation
[2,3]
[Figure 1]. Given the lack of data on prognosis, therapeutic options and management algorithms of MR in
this clinical setting, this review will focus on the percutaneous treatment of MR in patients with HFrEF.
In this setting, independent of the etiology of HFrEF, a higher degree of mitral regurgitation is strongly
associated with poor clinical outcomes, even though it remains uncertain if it is a direct contributor to
[5-7]
a worse prognosis or merely a marker of severity of the disease affecting the LV . As a matter of fact,
current European guidelines set lower thresholds for effective regurgitation orifice area (EROA) and
2
regurgitant volume (RVol) to define severe secondary MR (EROA ≥ 20 mm ; RVol ≥ 30 mL) compared to
2
that used for primary MR (EROA ≥ 40 mm ; RVol ≥ 60 mL) [1,8,9] . However, the definition of the severity
of MV disease remains a debated issue due to the poor reproducibility of EROA measurements, the close
dependence of the EROA and RVol values on LV volume, and lastly, the dynamic change of LV loading
conditions and performance after optimization of medical treatment [1,8,10-12] [Table 1]. Therefore, a careful
integration of quantitative, semiquantitative and qualitative echocardiographic parameters and clinical
data, is necessary for deciding appropriate treatment. Different from primary MR, there is no evidence
that surgical correction of valvular disease improves survival. Therefore, surgery is recommended only for
patients with symptomatic severe MR and a left ventricular ejection fraction (LVEF) > 30% undergoing
coronary artery by-bass graft, or in patients with lower EF but with evidence of myocardial viability and an
option for revascularization. Isolated MV surgery is burdened by significant operative mortality, high rates
of recurrent MR, absence of proven survival benefit and it may be considered in low surgical risk patients
remaining symptomatic despite optimal medical management, including cardiac resynchronization therapy
(CRT) with no markedly reduced LV function . In cases of suitable valve morphology, transcatheter
[1]
treatment remains an opportunity for higher surgical risk patients or for those without a revascularization
option, after careful Heart-Team evaluation. Based on current clinical guidelines, transcatheter repair of