Mitral Valve Disease

MITRAL VALVE DISEASE

Mitral Regurgitation (MR) accounts for the vast majority of all mitral valve diseases.¹ It has a prevalence of approximately 2% in the general population and is more common in the elderly population.³ Approximately 10% of people over the age of 70 have clinically meaningful MR.⁵

If left untreated, MR can lead to Heart Failure (HF), or deterioration of pre-existing HF, resulting in an increased number of hospital admissions and a substantial cost burden to health systems.^6,8

Summary of the current guidelines

Diagnosis of MR

PMR	SMR
Esc/eacts – Guidelines for the management of Valvular Heart Disease (2021)¹⁶
Evaluation Echocardiography is the first choice of imaging technique. EROA is strongly associated with all-cause mortality (starting from ≥20 mm2 and increasing beyond 40 mm2) Evaluation of the specific lesion leading to MR has prognostic implications. 3D TOE facilitates heart team discussion. CMR is a valid alternative to quantify regurgitant volume when echocardiographic parameters are inconsistent. Exercise echocardiography is particularly helpful in patients with discordant symptoms and regurgitation grade at rest. BNP values can be useful during follow-up. LV dimensions and ejection fraction should be considered to guide the management of patients with severe PMR. The MIDA score has been proposed to estimate the risk of all-cause mortality in patients with severe PMR due to flail leaflet, who are under medical treatment or surgically treated. Right heart catheterization is used to confirm pulmonary hypertension diagnosed by echocardiography when this is the only criterion to refer the patient for surgery.	Evaluation Echocardiographic criteria are the same as PMR. Lower thresholds for EROA and regurgitant volume may be applied to define severe SMR (≥30 mm2 likely corresponds to severe SMR, whether ≥20 mm2 defines severe SMR remains controversial). In HF patients, even mild MR is associated with poor prognosis; evidence suggests that surgical or transcatheter treatment of moderate SMR does not improve patient outcomes. Caution is therefore required 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. 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. 3D echocardiography, CMR, and exercise echocardiography may help to identify patients with severe MR when 2D echocardiography at rest is inconclusive.
ACC/AHA – GUIDELINES FOR THE MANAGEMENT OF PATIENTS WITH VALVULAR HEART DISEASE (2020)²²
Initial diagnosis In patients with known or suspected PMR, TTE is indicated for baseline evaluation of LV size and function, RV function, LA size, pulmonary artery pressure, and the mechanism and severity of primary MR (Stages A–D). (1; B-NR) When TTE provide insufficient or discordant information, TEE is indicated for evaluation of the severity of MR, mechanism of MR, and status of LV function (Stages B–D). (1;C-EO) CMR is indicated to assess LV and RV volumes and function and may help with assessing MR severity when there is a discrepancy between the findings on clinical assessment and echocardiography. (1; B-NR) In patients with severe PMR undergoing mitral intervention, intraoperative TEE is indicated to establish the anatomic basis for PMR (Stages C and D) and to guide repair. (1; B-NR) Changing signs or symptoms For PMR Stages B–D with new-onset or changing symptoms, TTE is indicated to evaluate the mitral valve apparatus and LV function. (1; B-NR) Routine follow-up For asymptomatic patients with severe PMR (Stages B and C1), TTE is indicated every 6–12 months for surveillance of LV function (estimated by LVEF, LVEDD, and LVESD) and assessment of pulmonary artery pressure. (1; B-NR) For asymptomatic patients with severe PMR (Stages B and C1), use of serum biomarkers and novel measurements of LV function, such as global longitudinal strain, may be considered as an adjunct to guide timing of intervention. (2b; B-NR) Exercise testing In patients with PMR (Stages B and C ), and symptoms that might be attributable to MR, haemodynamic exercise testing using Doppler echocardiography or cardiac catheterization or cardiopulmonary exercise testing is reasonable. (2a; B-NR)	Diagnosis In patients with chronic SMR (Stages B–D), TTE is useful to establish the aetiology and to assess the extent of regional and global LV remodelling and systolic dysfunction, severity of MR, and magnitude of pulmonary hypertension. (1; B-NR) In patients with chronic SMR (Stages B–D), non-invasive imaging (stress nuclear/PET, CMR, or stress echocardiography), coronary CT angiography, or coronary arteriography is useful to establish aetiology of MR and to assess myocardial viability. (1;C-EO) In patients with chronic SMR with severe symptoms (Stage D) that are unresponsive to GDMT who are being considered for transcatheter mitral valve interventions, TEE is indicated to determine suitability for the procedure. (1; B-NR) In patients with chronic SMR undergoing transcatheter mitral value intervention, intraprocedural guidance with TEE is recommended. (1;C-EO)

Abbreviations:
ACC, American College of Cardiology; AHA, American Heart Association; BNP, brain natriuretic peptide; CMR, cardiovascular magnetic resonance; CT, computed tomography; EACTS, European Association for Cardio-Thoracic Surgery; EROA, effective regurgitant orifice area; ESC, European Society of Cardiology; GDMT, guideline-directed medical therapy; HF, heart failure; LA, left atrium; LV, left ventricle; LVEDD, left ventricular end diastolic diameter; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; MIDA, Mitral Regurgitation International Database; MR, mitral regurgitation; OMT, optimal medical therapy; PET, positron emission tomography; PISA, proximal isovelocity surface area; PMR, primary mitral regurgitation; RV, right ventricle; SMR, secondary mitral regurgitation; TEE, transoesophageal echocardiography; TOE, transoesophageal echocardiogram; TR, tricuspid regurgitation; TTE, transthoracic echocardiography.

Medical management of MR

PMR	SMR
ACC/AHA – GUIDELINES FOR THE MANAGEMENT OF HEART FAILURE (2022)²⁸
N/A	In patients with chronic severe secondary MR and HFrEF, optimization of GDMT is recommended before any intervention for secondary MR related to LV dysfunction. (1; C-LD) GDMT, including RAAS inhibition, beta blockers, and biventricular pacing, improves MR and LV dimensions in patients with HFrEF and secondary MR, particularly MR that is proportionate to LV dilatation. A cardiologist with expertise in the management of HF is integral to shared decision-making for valve intervention and should guide optimization of GDMT to ensure that medical options for HF and secondary MR have been effectively applied for an appropriate time period and exhausted before considering intervention.
ESC/EACTS – GUIDELINES FOR THE MANAGEMENT OF VALVULAR HEART DISEASE (2021)¹⁶
In acute MR: 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 HF, medical treatment as per current HF guidelines applies.	Optimal GDMT for the management of HF, including replacement of ACEi or ARB with sacubitril/valsartan, sodium-glucose co-transporter 2 inhibitors and/or ivabradine, whenever indicated. Indications for CRT should be evaluated in accordance with related guidelines. If symptoms persist after optimisation of conventional HF therapy, options for mitral valve intervention should be promptly evaluated before further deterioration of LV systolic function or cardiac remodelling occur.
HFA/EACVI/EHRA/EAPCI/ESC JOINT POSITION STATEMENT ON THE MANAGEMENT OF SMR (2021)
N/A	Optimisation of GDMT in symptomatic moderate or severe SMR. Neurohormonal inhibitors, including ACEi, ARB, beta blockers, and mineralocorticoid receptor antagonists are mandatory in patients with HFrEF unless contraindicated or intolerable. Further pharmacological options in patients who remain symptomatic include ivabradine and replacement of ACEi or ARB with sacubitril/valsartan. Oral anticoagulation is essential in patients with AF.
ACC/AHA – GUIDELINES FOR THE MANAGEMENT OF PATIENTS WITH VALVULAR HEART DISEASE (2020)²²
In symptomatic or asymptomatic patients with severe PMR and LV systolic dysfunction (Stages C2 and D) in whom surgery is not possible or must be delayed, GDMT for systolic dysfunction is reasonable. (2a; B-NR) In asymptomatic patients with primary MR and normal LV systolic function (Stages B and C1), vasodilator therapy is not indicated if the patient is normotensive. (3; B-NR)	Patients with chronic severe SMR (Stages C and D) and HF with reduced LVEF should receive standard GDMT for HF, including ACE inhibitors, ARBs, beta blockers, aldosterone antagonists, and/or sacubitril/valsartan, and biventricular pacing as indicated. (1; A) In patients with chronic severe SMR and HF with reduced LVEF, a cardiologist expert in the management of patients with HF and LV systolic dysfunction should be the primary MDT member responsible for implementing and monitoring optimal GDMT. (1; C-EO)

Surgical management of MR

PMR	SMR
ACC/AHA – GUIDELINE FOR THE MANAGEMENT OF HEART FAILURE (2022)²⁸
N/A	Patients with persistent severe secondary MR despite GDMT may benefit from either surgical or transcatheter repair, depending on clinical scenario. Thus, patient-centric conversation with a multidisciplinary cardiovascular team that includes a cardiologist with expertize in HF is essential when considering MV intervention.
ESC/EACTS – GUIDELINES ON THE MANAGEMENT OF VALVULAR HEART DISEASE (2021)¹⁶
Mitral valve repair is the recommended surgical technique when the results are expected to be durable. (I B). Surgery is recommended in symptomatic patients who are operable and not high risk. (I B). Surgery is recommended in asymptomatic patients with LV dysfunction (LVESD ≥40 mm and/or LVEF ≤60%). (I B). Surgery should be considered in asymptomatic patients with preserved LV function (LVESD <40 mm and LVEF >60%) and AF secondary to MR or pulmonary hypertension (SPAP at rest >50 mmHg). (IIa B). Surgical mitral valve repair should be considered in low-risk asymptomatic patients with LVEF >60%, LVESD <40 mm and significant LA dilatation (volume index ≥60 mL/m2 or diameter ≥55 mm) when performed in a Heart Valve Center and a durable repair is likely. (IIa B).	Valve surgery/intervention is recommended only in patients with severe SMR who remain symptomatic despite GDMT (including CRT if indicated) and has to be decided by a structured collaborative Heart Team. (I B). Patients with concomitant coronary artery or other cardiac disease requiring treatment: Valve surgery is recommended in patients undergoing CABG or other cardiac surgery. (I B). Patients without concomitant coronary artery or other cardiac disease requiring treatment: Valve surgery may be considered in symptomatic patients judged appropriate for surgery by the Heart Team. (IIb C).
ESC – GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE AND CHRONIC HF (2021)¹⁵
N/A	In patients with HF, severe SMR, and CAD who need revascularization, CABG and mitral valve surgery should be considered. (IIa C).
HFA/EACVI/EHRA/EAPCI/ESC JOINT POSITION STATEMENT ON THE MANAGEMENT OF SMR IN PATIENTS WITH HF (2021)²⁹
N/A	Decisions concerning treatments for MR, other than pharmacological therapy or circulatory support, should ideally be made in stable patients without fluid overload or the need for inotropic support. Surgical treatment of severe SMR should be considered in operable patients with coronary artery disease requiring surgical revascularization. Circulatory support devices and cardiac transplantation should be considered as an alternative in patients with advanced left and/or right ventricular failure. Interventions for MR should be avoided in patients with life expectancy <1 year due to conditions unrelated to the MR. Interventions for MR should be avoided in patients with life expectancy <1 year due to conditions unrelated to the MR.
ACC/AHA – GUIDELINES FOR THE MANAGEMENT OF PATIENTS WITH VALVULAR HEART DISEASE (2020)²²
In symptomatic patients with severe PMR (Stage D), mitral valve intervention is recommended irrespective of LV systolic function. (1; B-NR). In asymptomatic patients with severe PMR and LV systolic dysfunction (LVEF ≤60%, LVESD ≥40 mm) (Stage C2), mitral valve surgery is recommended. (1; B-NR). In patients with severe PMR for whom surgery is indicated, mitral valve repair is recommended in preference to mitral valve replacement when the anatomic cause of MR is degenerative disease, if a successful and durable repair is possible. (1; B-NR). In asymptomatic patients with severe PMR and normal LV systolic function (LVEF ≥60% and LVESD ≤40 mm) (Stage C1), mitral valve repair is reasonable when the likelihood of a successful and durable repair without residual MR is >95% with an expected mortality rate of <1%, when it can be performed at a Primary or Comprehensive Valve Center. (2a; B-NR). In asymptomatic patients with severe PMR and normal LV systolic function (LVEF >60% and LVESD <40 mm) (Stage C1) but with a progressive increase in LV size or decrease in EF on ≥3 serial imaging studies, mitral valve surgery may be considered irrespective of the probability of a successful and durable repair. (2b; C-LD). In symptomatic patients with severe PMR attributable to rheumatic valve disease, mitral valve repair may be considered at a Comprehensive Valve Center by an experienced team when surgical treatment is indicated, if a durable and successful repair is likely. (2b; B-NR).	In patients with severe SMR (Stages C and D), mitral valve surgery is reasonable when CABG is undertaken for the treatment of myocardial ischaemia. (2a; B-R). In patients with chronic severe SMR from atrial annular dilation with preserved LV systolic function (LVEF ≥50%) who have severe persistent symptoms (NYHA class III or IV) despite therapy for HF and therapy for associated AF or other comorbidities (Stage D), mitral valve surgery may be considered. (2b; B-NR). In patients with chronic severe SMR related to LV systolic dysfunction (LVEF<50%) who have persistent severe symptoms (NYHA class III or IV) while on optimal GDMT for HF (Stage D), mitral valve surgery may be considered. (2b; B-NR). In patients with CAD and chronic severe SMR related to LV systolic dysfunction (LVEF<50%) (Stage D) who are undergoing mitral valve surgery because of severe symptoms (NYHA class III or IV) that persist despite GDMT for HF, chordal-sparing mitral valve replacement may be reasonable to choose over downsized annuloplasty repair. (2b; B-R).

Abbreviations:
ACC, American College of Cardiology; AF, atrial fibrillation; AHA, American Heart Association; AV, atrioventricular; CABG, coronary artery bypass grafting; CAD, coronary artery disease; CRT, cardiac resynchronization therapy; EACTS, European Association for Cardio-Thoracic Surgery; EACVI, European Association of Cardiovascular Imaging; EAPCI, European Association of Percutaneous Cardiovascular Interventions; EHRA, European Heart Rhythm Association; ESC, European Society of Cardiology; GDMT, guideline-directed medical therapy; HF, heart failure; HFA, Heart Failure Association; LA, left atrium; LV, left ventricle; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; MR, mitral regurgitation; NA, not applicable; NYHA, New York Heart Association; PMR, primary mitral regurgitation; SMR, secondary mitral regurgitation; SPAP, systolic pulmonary artery pressure.

TMVr management of MR

PMR	SMR
ACC/AHA – GUIDELINE FOR THE MANAGEMENT OF HEART FAILURE (2022)²⁸
N/A	Patients with persistent severe secondary MR despite GDMT may benefit from either surgical or transcatheter repair, depending on clinical scenario. Thus, patient-centric conversation with a multidisciplinary cardiovascular team that includes a cardiologist with expertize in HF is essential when considering MV intervention. Specifically, MV TEER has been shown to be beneficial in patients with persistent symptoms despite GDMT, appropriate anatomy on transesophageal echocardiography, LVEF between 20–50%, LVESD ≤70 mm, and pulmonary artery systolic pressure ≤70 mm Hg.
ESC/EACTS – GUIDELINES FOR THE MANAGEMENT OF VALVULAR HEART DISEASE (2021)¹⁶
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. (IIb B; see also Figure 8).	Patients with concomitant coronary artery or other cardiac disease requiring treatment: In symptomatic patients, who are judged not appropriate for surgery by the Heart Team on the basis of their individual characteristics, PCI (and/or TAVI) possibly followed by TEER (in case of persisting severe SMR) should be considered. (IIa C). Patients without concomitant coronary artery or other cardiac disease requiring treatment: TEER should be considered in selected symptomatic patients, not eligible for surgery and fulfilling criteria suggesting an increased chance of responding to the treatment. (IIa B). In high-risk symptomatic patients not eligible for surgery and not fulfilling the criteria suggesting an increased chance of responding to TEER, the Heart Team may consider in selected cases a TEER procedure or other transcatheter valve therapy if applicable, after careful evaluation for ventricular assist device or heart transplant. (IIb C).
ESC – GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE AND CHRONIC HF (2021)¹⁵
N/A	Percutaneous edge-to-edge mitral valve repair should be considered in carefully selected patients with SMR, not eligible for surgery and not needing coronary revascularization, who are symptomatic despite OMT and who fulfil criteria to achieve a reduction in HF hospitalizations. (IIa). Percutaneous edge-to-edge mitral valve repair may be considered to improve symptoms in carefully selected patients with SMR, not eligible for surgery and not needing coronary revascularization, who are highly symptomatic despite OMT and who do not fulfil criteria for reducing HF hospitalization. (IIb).
HFA/EACVI/EHRA/EAPCI/ESC JOINT POSITION STATEMENT ON THE MANAGEMENT OF SMR IN PATIENTS WITH HF (2021)²⁹
N/A	TEER is an evidence-based treatment option in patients with severe SMR who remain symptomatic despite GDMT (including CRT when indicated) and who have been carefully selected by a multidisciplinary Heart Team. Interventions for MR should be avoided in patients with life expectancy <1 year due to conditions unrelated to the MR.
ACC/AHA – GUIDELINES FOR THE MANAGEMENT OF PATIENTS WITH VALVULAR HEART DISEASE (2020)²²
In severely symptomatic patients (NYHA class III or IV) with primary PMR and high or prohibitive surgical risk, TEER is reasonable if mitral valve anatomy is favorable for the repair procedure and patient life expectancy is at least 1 year. (2a; B-NR)	In patients with chronic severe SMR related to LV systolic dysfunction (LVEF <50%) who have persistent symptoms (NYHA class II, III, or IV) while on optimal GDMT for HF (Stage D), TEER is reasonable in patients with appropriate anatomy as defined on TEE and with LVEF between 20% and 50%, LVESD ≤70 mm, and pulmonary artery systolic pressure ≤70 mmHg. (2a; B-R).

Abbreviations:
ACC, American College of Cardiology; AHA, American Heart Association; CRT, cardiac resynchronization therapy; EACTS, European Association for Cardio-Thoracic Surgery; EACVI, European Association of Cardiovascular Imaging; EAPCI, European Association of Percutaneous Cardiovascular Interventions; EHRA, European Heart Rhythm Association; ESC, European Society of Cardiology; GDMT, guideline-directed medical therapy; HF, heart failure; HFA, Heart Failure Association; LV, left ventricle; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; MR, mitral regurgitation; NA, not applicable; NYHA, New York Heart Association; OMT, optimal medical therapy; PCI, percutaneous coronary intervention; PMR, primary mitral regurgitation; QoL, quality of life; SMR, secondary mitral regurgitation; TAVI, transcatheter aortic valve implantation; TEE, transoesophageal echocardiography; TEER, transcatheter edge-to-edge repair.

TMVR management of MR

PMR	SMR
ESC/EACTS – GUIDELINES FOR THE MANAGEMENT OF VALVULAR HEART DISEASE (2021)¹⁶
N/A	TMVR is also emerging as a possible alternative option, but randomized trials are still lacking.
ESC GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE AND CHRONIC HF (2021)¹⁵
N/A	TMVR is also emerging as a possible alternative option, but randomized trials are still lacking.
ACC/AHA – GUIDELINES FOR THE MANAGEMENT OF PATIENTS WITH VALVULAR HEART DISEASE (2020)²²
In patients with severe PMR for whom surgery is indicated, TMVr is recommended in preference to TMVR when the anatomic cause of MR is degenerative disease, if a successful and durable repair is possible. (1; B-NR). In patients with severe PMR where leaflet pathology is limited to less than one half the posterior leaflet, TMVR should not be performed unless TMVr has been attempted at a Primary or Comprehensive Valve Center and was unsuccessful. (3; B-NR).	In patients with CAD and chronic severe SMR related to LV systolic dysfunction (LVEF <50%) (Stage D) who are undergoing MV surgery because of severe symptoms (NYHA class III or IV) that persist despite GDMT for HF, chordal-sparing TMVR may be reasonable to choose over downsized annuloplasty repair. (2b; B-R).

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