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...................................... or considered at high risk, then percutaneous repair may be considered.592,605

Secondary (functional) mitral regurgitation Secondary mitral regurgitation (SMR) is mostly a disease of the left ventricle. It can also be caused by mitral annulus enlargement due to LA dilation.606 Moderate or severe SMR is associated with an extremely poor prognosis in patients with HF.607,608 The assessment of MR aetiology and severity should be performed by an experienced echocardiographer applying a multi-parametric approach, and ideally in stable patient conditions, after optimization of medical and resynchronization therapies. Being SMR a dynamic condition, echocardiographic quantification during exercise may be helpful in patients with moderate SMR at rest and symptoms during physical activity.609 Early referral of patients with HF and moderate or severe MR to a multidisciplinary Heart Team, including HF specialists, is recommended for assessment and treatment planning. The Heart Team has to verify, first of all, that the patient is on optimal therapy, including CRT, when indicated (Figure 17). In patients with severe SMR and HFrEF requiring revascularization, mitral valve surgery and CABG should be considered. Isolated mitral valve surgery may be considered in symptomatic patients with severe SMR despite optimal therapy and low surgical risk.592 Two randomized trials, MITRA-FR and COAPT, evaluated the effectiveness of percutaneous edge-to-edge mitral valve repair plus OMT compared to OMT alone, in symptomatic patients with reduced LVEF (1540% in MITRA-FR and 2050% in COAPT) and moderate-to-severe or severe SMR [effective regurgitant orifice area (EROA) >_ 20 mm2 in MITRA-FR and EROA >_ 30 mm2 in COAPT].610612 MITRA-FR failed to show any benefit from the intervention on all-cause mortality or HF hospitalization at 12 months (primary endpoint; HR 1.16, 95% CI 0.731.84) and at 24 months.610,611 In contrast, COAPT showed a significant reduction in hospitalization for HF at 24 months (primary endpoint; HR 0.53, 95% CI 0.400.70) and mortality (secondary endpoint; HR 0.62, 95% CI 0.460.82).612 Differences in patient selection, concomitant MT, echocardiographic assessment, procedural issues and severity of SMR in relation to the degree of LV dilatation may be responsible for the diverging results of the MITRA-FR and COAPT trials.613615 Thus, percutaneous edge-to-edge mitral valve repair should be considered for outcome improvement only in carefully selected patients who remain symptomatic (NYHA class IIIV) despite OMT, with moderate-to-severe or severe SMR (EROA >_30 mm2), favourable anatomical conditions, and fulfilling the inclusion criteria of the COAPT study (i.e. LVEF 2050%, LV end-systolic diameter <70 mm, systolic pulmonary pressure <70 mmHg, absence of moderate or severe RV dysfunction, absence of severe TR, absence of haemodynamic instability) (Figure 17).615,616 Percutaneous edge-to-to edge mitral valve repair may also be considered to improve symptoms in patients with advanced HF, severe SMR and severe symptoms despite OMT. In these patients, cardiac transplantation or LVAD implantation must also be considered.376,617 Other percutaneous mitral valve repair systems, such as indirect annuloplasty, are available for treatment of SMR. This approach has a shorter learning curve and lesser technical requirements than percutaneous edge-to-to edge mitral valve repair and does not preclude different procedures once it is performed. A sham-controlled randomized trial testing a transcatheter indirect mitral annuloplasty device met its primary endpoint of mitral regurgitant volume reduction with reverse LV and LA remodelling at 12 months.618 Further studies confirmed favourable results on LA volumes and LV remodelling with trends towards improvement in mean 6MWT distance and symptoms and a reduction in HF hospitalizations in an IPD meta-analysis.619622 Transcatheter mitral valve replacement is also emerging as a possible alternative option, but randomized trials are still lacking.623

Mitral valve interventions are not recommended in patients with a life expectancy of <1 year due to extra-cardiac conditions.592

Recommendations for the management of valvular heart disease in patients with heart failure

Recommendations Classa Levelb

Aortic stenosis Aortic valve intervention, TAVI or SAVR, is recommended in patients with HF and severe highgradient aortic stenosis to reduce mortality and improve symptoms.594 I B It is recommended that the choice between TAVI and SAVR be made by the Heart Team, according to individual patient preference and features including age, surgical risk, clinical, anatomical and procedural aspects, weighing the risks and benefits of each approach.592 I C Secondary mitral regurgitation Percutaneous edge-to-edge mitral valve repair should be considered in carefully selected patients with secondary mitral regurgitation, not eligible for surgery and not needing coronary revascularization, who are symptomaticc despite OMT and who fulfil criteriad for achieving a reduction in HF hospitalizations.612 IIa B In patients with HF, severe secondary mitral regurgitation and CAD who need revascularization, CABG and mitral valve surgery should be considered. IIa C Percutaneous edge-to-edge mitral valve repair may be considered to improve symptoms in carefully selected patients with secondary mitral regurgitation, not eligible for surgery and not needing coronary revascularization, highly symptomatic despite OMT and who do not fulfil criteria for reducing HF hospitalization.617 IIb C

CABG = coronary artery bypass graft; CAD = coronary artery disease; LVEF = left ventricular ejection fraction; LVESD = left ventricular end-systolic diameter; NYHA = New York Heart Association; OMT = optimal medical therapy; SAVR = surgical aortic valve replacement; TAVI = transcatheter aortic valve implantation; TR = tricuspid regurgitation. aClass of recommendation. bLevel of evidence. cNYHA class IIIV. dAll of the following criteria must be fulfilled: LVEF 2050%, LVESD <70 mm, systolic pulmonary pressure <70 mmHg, absence of moderate or severe right ventricular dysfunction or severe TR, absence of haemodynamic instability.612 ESC 2021

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