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Page 6 of 14 Stolz et al. Mini-invasive Surg 2020;4:76 I http://dx.doi.org/10.20517/2574-1225.2020.69

SMR only collective
Consistently, impaired LV-EF leads to significantly worsened long-term survival in patients with SMR after
[49]
TMVr [25,46-48] . In contrast to mixed cohort analysis, severe LV dilatation, measured either by LV-EDD or
[48]
left ventricular end diastolic volume , was identified as a predictor for all-cause mortality in patients with
SMR [Table 1]. After publication of the COAPT and MITRA-FR trials, a discussion about possible reasons
for the diverging prognostic results has evolved and several explanations have been proposed. Among
them are operator experience, intensity of concomitant medical therapy, progression of heart failure at
baseline, and procedural MR reduction. Since mean left ventricular end diastolic volume was very high
in MITRA-FR, patients in this trial might have had end-stage heart failure with severe LV dilatation. The
proportionality of MR severity to LV dilatation, quantified by ratio of effective regurgitant orifice area to
LV end diastolic volume, has recently gained attention [14,50] . Latest analyses showed that the proportionality
concept as a prognostic framework might be applicable to medically treated SMR patients. Its influence on
prognosis in TMVr-treated patients is probably less important, as TMVr effectively reduces MR and thus
abolishes one component of the proportionality equation [17,19] .

LEFT ATRIAL FUNCTION AND DIMENSIONS
Composed PMR and SMR patient collective
Atrial fibrillation or absence of sinus rhythm, as indicators of impaired LA function in addition to LA
dilation, are linked to worse TMVr survival [42,51,52] . Severe LA dilatation with a diameter ≥ 55 cm seems to
[52]
be a highly predictive cut-off value . In contrast, improvement of LA ejection fraction from baseline to
[53]
short term follow up (three to six month) is associated with lower all-cause long-term mortality [Table 1].
SMR only collective
[47]
While dedicated data for PMR patients are missing, atrial fibrillation [47,48] and increased LA volume
are associated with impaired long-term survival in SMR patients [Table 1]. Left atrial dysfunction in
SMR patients recently gained attention as this condition can lead to MR in absence of severe systolic LV
dysfunction. This pathology called atrial secondary mitral regurgitation (ASMR) is caused by either atrial
fibrillation or heart failure with preserved ejection fraction (HFpEF), as both increase LA pressure and
volume leading to annular flattening and alteration of left ventricular atrioventricular hemodynamics .
[54]
As HFpEF patients with SMR were excluded from large controlled randomized trials (COAPT or MITRA-
FR) [12,13] , but undergo TMVr procedure in real-world clinical practice, impact of ASMR on survival and
procedural success warants further investigation.

MITRAL VALVE ANATOMY, HEMODYNAMICS, AND PROCEDURAL SUCCESS
Composed PMR and SMR patient collective
Elevated MV mean PG was identified as highly predictive in terms of all-cause mortality, both for
preprocedural and postprocedural measurements. TMVr increases MV mean PG by reduction of mitral
valve opening area [27,36,55] [Table 2]. Additionally, previous MV surgery has been reported to have negative
[56]
influence on long-term outcome . Success of TMVr procedure itself is crucial for reduction of long-term
mortality and reflects the benefit of this interventional approach on MR treatment. Absence of procedural
MR reduction and residual MR after procedure lead to severely impaired long-term survival [25,35,36,56-60] [Table 2].

PMR only collective
[61]
In PMR patients, postprocedural MV mean PG is a significant predictor for survival [Table 2].

SMR only collective
Similar to findings in the composed SMR/PMR collective, residual SMR is a major factor contributing
to mortality following TMVr procedure [33,49] . In particular, postprocedural MR vena contracta area is