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6.1.3 Medical therapy In acute mitral regurgitation, nitrates and diuretics are used to reduce filling pressures. Sodium nitroprusside reduces afterload and regurgitant fraction. Inotropic agents and an intra-aortic balloon pump are of use in hypotension and haemodynamic instability. In chronic PMR with preserved LVEF, there is no evidence to support the prophylactic use of vasodilators. In patients with overt heart failure, medical treatment as per current heart failure guidelines applies.247

6.1.4 Serial testing Asymptomatic patients with severe mitral regurgitation and LVEF >60% should be followed clinically and by echocardiography every 6 months, ideally in the setting of a Heart Valve Centre.309 Measurement of BNP levels, exercise echocardiography, electrocardiogram-Holter monitoring and CMR are useful complementary diagnostic and risk stratification tools.268 The association between PMR, sudden cardiac death and ventricular arrhythmias remains controversial.310312 The presence of mitral annulus disjunction (abnormal atrial displacement of the hinge point of the mitral valve away from the ventricular myocardium) has been also associated with increased risk of ventricular arrhythmias.310,311,313 Interestingly, the majority of these patients did not have severe mitral regurgitation. In asymptomatic patients with severe PMR and progressive increase of LV size (LVESD approaching 40 mm) or decrease of LVEF on serial studies, surgical mitral valve repair should be discussed. Asymptomatic patients with moderate mitral regurgitation and preserved LV function can be followed on a yearly basis and echocardiography should be performed every 12 years. After intervention, serial follow-up focuses on evaluation of symptomatic status, presence of arrhythmic events, assessment of valve function,314 and recurrence of mitral regurgitation. After surgical mitral valve repair, high-volume centres have reported good durability with a recurrence rate of moderate or severe mitral regurgitation of 12.5% at 20 years of follow-up.296 After transcatheter mitral valve repair, the currently reported rates of residual moderate and severe mitral regurgitation (2330%) would suggest that yearly echocardiogram is appropriate.14,300,301 6.1.5 Special populations Sex differences in terms of prevalence of underlying aetiology of PMR and management have been reported.298,315,316 Despite the reduction in the prevalence of rheumatic disease in Western countries, women still have higher rates of rheumatic mitral regurgitation than men and emerging aetiologies such as radiation heart disease are also more frequent in women.297 These aetiologies are often characterized by severe calcification of the mitral valve apparatus and associated with mitral stenosis precluding durable repair. Women with PMR referred for surgical treatment received mitral valve repair at a similar rate to men.316 However, women more frequently present with post-operative heart failure, probably related to a later referral and more advanced disease as compared to men.

6.2 Secondary mitral regurgitation

In SMR, the valve leaflets and chordae are structurally normal and mitral regurgitation results from an imbalance between closing and tethering forces secondary to alterations in LV and LA geometry.317,318 It is most commonly seen in dilated or ischaemic cardiomyopathies, both in severely dilated LV with markedly depressed LV function or after an isolated infero-basal myocardial infarction leading to posterior leaflet tethering, despite almost normal LV size and ejection fraction. SMR may also arise as a consequence of LA enlargement and mitral annular dilatation in patients with longstanding AF, in whom LVEF is usually normal and LV dilatation less pronounced (so called ‘atrial functional mitral regurgitation’).319

6.2.1 Evaluation The echocardiographic criteria to define severe SMR do not differ from those used in PMR and an integrative approach should be used (Table 7).24,268 However, it should be acknowledged that when quantifying EROA and regurgitant volume in SMR, lower thresholds may be applied to define severe SMR. In heart failure patients, the total forward LV stroke volume is lower and that may lead to lower estimated regurgitant volume (<60 mL/beat). Calculation of regurgitant fraction in those circumstances could account for lower flows and has shown prognostic implications.320 In addition, the crescent shape of the regurgitant orifice, characteristic of SMR, may lead to underestimation of the vena contracta width and of the EROA. An EROA >_30 mm2 by 2D proximal isovelocity surface area (PISA) likely corresponds to severe SMR. In contrast, whether an EROA >_20 mm2 defines severe SMR remains controversial. In heart failure patients, even mild mitral regurgitation is associated with poor prognosis321 and evidence that surgical or transcatheter treatment of moderate SMR does not seem to improve patient outcomes322,323 supports the change in definition of severe SMR. Caution is required, therefore, when labelling severe SMR based solely on prognostic implications. Other factors such as the extent of myocardial scar, as assessed with CMR, have been associated with poor prognosis.324 In addition, LVEF has been shown to be misleading in patients with severe SMR, while LV global longitudinal strain has been shown to have incremental prognostic value.325,326 The use of 3D echocardiography, CMR and exercise echocardiography may help to identify patients with severe mitral regurgitation when 2D echocardiography at rest is inconclusive.24,268

Surgical mitral valve repair should be considered in low-risk asymptomatic patients with LVEF >60%, LVESD <40 mmd and significant LA dilatation (volume index >_60 mL/m2 or diameter >_55 mm) when performed in a Heart Valve Centre and a durable repair is likely.285,288 IIa B TEER may be considered in symptomatic patients who fulfil the echocardiographic criteria of eligibility, are judged inoperable or at high surgical risk by the Heart Team and for whom the procedure is not considered futile.299302 IIb B

AF = atrial fibrillation; LA = left atrium/left atrial; LV = left ventricle/left ventricular; LVEF = left ventricular ejection fraction; LVESD = left ventricular end-systolic

to-edge repair. aClass of recommendations. bLevel of evidence. cIf an elevated SPAP is the only indication for surgery, the value should be confirmed by invasive measurement. dCut-offs refer to average-size adults and may require adaptations in patients with unusually small or large stature. ESC/EACTS 2021

diameter; SPAP = systolic pulmonary arterial pressure; TEER = transcatheter edge- Downloaded from academic.oup.com/eurheartj/article/43/7/561/6358470 by guest on 07 October 2026