Severe Primary Mitral Regurgitation Research Articles

The MITRA-HR study: design and rationale of a randomised study of MitraClip transcatheter mitral valve repair in patients with severe primary mitral regurgitation eligible for high-risk surgery.

Percutaneous mitral valve repair has become an alternative to conventional surgery in patients suffering primary mitral regurgitation (MR) with a contraindication to surgery and could benefit patients at high surgical risk. The aim of the MITRA-HR study is to raise the level of evidence supporting the use of the MitraClip device in primary MR patients with a predefined high risk for surgery. MITRA-HR is a prospective, multicentre, randomised study designed to compare mitral valve repair using the MitraClip with conventional surgery in patients with severe primary mitral regurgitation at high risk for surgery. The surgical risk is defined by age, Society of Thoracic Surgeons (STS) risk estimate score, frailty, major organ system dysfunction, and procedure-specific impediments. The study will enrol 330 patients randomised between conventional surgery and MitraClip with a 1:1 ratio. The composite primary endpoint includes all-cause mortality, unplanned rehospitalisation for cardiovascular reasons, and mitral valve reintervention at 12 months. The main secondary safety endpoint is a major adverse event composite assessment evaluated 30 days after the procedure. The randomised MITRA-HR study is designed to provide additional supportive evidence of non-inferiority in efficacy and superiority in safety for percutaneous mitral valve repair using the MitraClip compared to conventional surgery in high surgical risk patients.

Prognostic Value of Global Longitudinal Strain and Etiology After Surgery for Primary Mitral Regurgitation

ObjectivesThis study sought to investigate whether left ventricular (LV) global longitudinal strain (GLS) is associated with long-term outcome after mitral valve (MV) surgery for primary mitral regurgitation (MR) and assess the differences in outcome according to MR etiology: Barlow’s disease (BD), fibroelastic deficiency (FED), and forme fruste (FF). BackgroundAppropriate timing of MV surgery for primary MR is still challenging and may differ according to the etiology. In these patients, LV-GLS has been proposed as more sensitive measure to detect subtle LV dysfunction as compared with LV ejection fraction. MethodsEchocardiography was performed in 593 patients (64% men, age 65 ± 12 years) with severe primary MR who underwent MV surgery, including assessment of LV-GLS. The etiology (BD, FED, or FF) was defined based on surgical observation. During follow-up, primary endpoint was all-cause mortality and a secondary endpoint included cardiovascular death, heart failure hospitalizations, and cerebrovascular accidents. ResultsDuring a median follow-up of 6.4 (interquartile range: 3.6 to 10.4) years, 146 patients died (16 within 30 days after surgery), 46 patients were hospitalized for heart failure, and 13 patients had a cerebrovascular accident. Age (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.05 to 1.11; p < 0.001) and LV-GLS (HR: 1.13; 95% CI: 1.06 to 1.21; p < 0.001) were independently associated with all-cause mortality. Patients with LV-GLS >–20.6% (more impaired) showed significant worse survival than did patients with LV-GLS ≤–20.6%; of interest, patients with BD showed similar prognosis compared with FED and FF. In addition, previous atrial fibrillation (HR: 1.70; 95% CI: 1.01 to 2.86; p = 0.045) and LV-GLS (HR: 1.01; 95% CI: 1.01 to 1.15; p = 0.019) were independently associated with the secondary endpoint. ConclusionsLV-GLS is independently associated with all-cause mortality and cardiovascular events after MV surgery for primary MR and might be helpful to guide surgical timing. Importantly, patients with BD showed similar prognosis when corrected for age, compared with patients with FED or FF.

2019 AATS/ACC/ASE/SCAI/STS expert consensus systems of care document: A proposal to optimize care for patients with valvular heart disease: A Joint Report of the American Association for Thoracic Surgery, American College of Cardiology, American Society of Echocardiography, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

This statement was commissioned as a Multisociety Expert Consensus Systems of Care Document by the American Association for Thoracic Surgery (AATS), American College of Cardiology (ACC), American Society of Echocardiography (ASE), Society for Cardiovascular Angiography and Interventions (SCAI), and

FLOATING LEFT ATRIAL MASS IN A PATIENT WITH PROSTHETIC MITRAL VALVE: MANAGEMENT DILEMMA

A giant mobile left atrial mass in a patient with prosthetic mitral valve (MV) with significant co morbidities created a challenging clinical scenario and treatment dilemma. A 53 year old male with history of primary severe mitral regurgitation status post unsuccessful mitral valve repair, redo

75-Year-Old Man With Chest Pain and Dyspnea

75-Year-Old Man With Chest Pain and Dyspnea

Novel mitral valve technologies-transcatheter mitral valve implantation: a systematic review.

Valvular heart disease is an important cause of morbidity and mortality throughout the world; in industrialized nations, mitral regurgitation (MR) is the most common valvular lesion. Untreated, severe MR has a poor prognosis, with a 5-year mortality rate of up to 50%. Surgical repair of symptomatic, severe primary MR has been demonstrated to improve survival. The aim of this review is to assess the early outcomes of newly developed transcatheter mitral valve implantation technologies for the treatment of secondary native valve disease. Furthermore, the outcomes of patients receiving transcatheter treatment of regurgitant failure of surgically repaired or replaced mitral valve has also been addressed. A systematic review of twenty-five studies assessing the outcomes of patients undergoing transcatheter mitral valve implantation for native mitral regurgitation or failed prior surgical repair or bioprosthetic replacement was carried out. The outcomes of 112 patients undergoing transcatheter mitral valve replacement for secondary mitral regurgitation using six different valve systems were assessed. There were 15 early deaths and 24 deaths over the follow-up period. The outcomes of 44 patients undergoing transcatheter valve-in-valve replacement were assessed with an overall mortality of ten patients. There were 20 patients included who had valve-in-ring transcatheter mitral replacement for previous failed repair. The total mortality was five patients during the follow-up period. Transcatheter mitral valve implantation represents a new evolution in management of valvular disease and affords management options to patients who historically may not have been offered treatment. Early results have demonstrated some promise and improvements in technology, imaging modalities and patient selection will surely result in a reliable and durable valve.

RF87 TRANSAPICAL OFF-PUMP MITRAL VALVE REPAIR WITH PTFE CHORD IMPLANTATION

Background: NeoChord DS-1000 system (NeoChord,Inc,Minneapolis, Minnesota)is a novel minimally invasive technique of mitral valve repair (MVR)consisting in off-pump beating heart transapical implantation of artificial neo-chordae under TEE guide. Aim: To evaluate the feasibility,safety and up to 12 months outcome of the NeoChord DS-1000 system in patients with primary mitral regurgitation (MR),due to leaflet(s) prolapse or flail. Methods: From July 2015 to November 2016,34 patients with severe primary MR were selected for transapical Neochordae implantation at 3 centers in Italy. Mitral Valve Academic Research Consortium (MVARC) procedural success criteria were evaluated in all patients at 30 days,6 and 12 months. Results: Mean age was 64.7 ± 11 years,mean STS repair score was 1.06%(IQR 0.46-1.12).25 patients had isolated P2 disease and 9 patients had other or multisegment disease involvement. MR ≤moderate at 30 days was achieved in 91%of patients. In hospital mortality was 2.9% for respiratory failure,and 2 patients had undergone conversion to traditional valve surgery for functional failure and residual significant MR. At discharge 80.6% patients had MR ≤mild and 17% patients had moderate MR.2 patients experienced early device failure with recurrent sever MR and had undergone additional valve surgery (at 61 and 129 days after implantation).22 patients reached 6 month follow up,all had MR ≤moderate and showed significant improvement in NYHA functional class (P &lt; 0.005).10 patients reached 12 month follow up,all had MR ≤moderate and 90% had NYHA class I. Conclusion: Mitral valve repair with the NeoChord DS-1000 system for primary MR due to leaflet(s) prolapse or flail is feasible and safe.Its efficacy is maintained up to 1 year showing significant clinical benefit and functional class improvement.

Traitement percutané de l’insuffisance mitrale par Mitraclip chez le sujet âgé

Mitral regurgitation (MR) is the second most common form of valvular heart disease. It is classified as either primary (degenerative) or secondary (functional). Secondary MR is the consequence of myocardium disease. Primary MR from degenerative valve disease is due to a primary disruption of the mitral valve apparatus from either prolapsed or flail leaflets. It covers all aetiologies in which intrinsic lesions affect one or several components of the mitral valve apparatus. Gold-standard therapeutic management of severe primary MR is surgery usually to repair but sometime to replace the mitral valve. However patients considered to be at high-risk due to their age or the presence of comorbidities – accounting for 50% of all patients – are not eligible for surgery. Catheter-based interventions have been developed to correct MR percutaneously. The only such intervention which has been evaluated in organic MR is the edge-to-edge procedure using the MitraClip® (Abbott Vascular, Menlo Park, CA). MitraClip® offers an alternative to open surgical repair or replacement via a minimally invasive route and it was shown in the EVEREST II study that MitraClip® was safer than surgery even though it was less effective in reducing MR. A substantial number of patients are ineligible for mitral valve surgery because of prohibitive surgical risk. For those patients, MitraClip® may offer an alternative treatment option. Percutaneous edge-to-edge repair is the first percutaneous option accepted in the 2012 ESC guidelines: Percutaneous edge-to-edge procedure may be considered in patients with symptomatic severe primary MR who fulfill the echo criteria of eligibility, are judged inoperable or at high surgical risk by a ‘heart team’, and have a life expectancy greater than 1 year (recommendation class IIb, level of evidence C). Because of its frailty, MitraClip® in the elderly may be a good alternative to mitral surgery when indicated for primary or secondary MD.

Mitral valve repair versus replacement for patients with preserved left ventricular function without heart failure symptoms

ObjectiveThe purposes of this study are to compare outcomes of mitral valve repair (MV-repair) and mitral valve replacement for patients with severe mitral regurgitation with preserved ventricular function and no congestive heart failure (CHF) symptoms and to examine variations in surgeon choice of procedure and outcomes by surgeon volume. MethodsIn total, 2259 consecutive patients in 42 New York State hospitals with the characteristics mentioned previously who underwent mitral valve repair (1801, 79.7%) or replacement between January 1, 2008, and December 31, 2014, were identified from a mandatory statewide clinical registry. Propensity-matching was used to compare mortality and competing risk analyses were used to compare nonfatal outcomes. Median follow-up was 4.0 years. The use of mitral repair and risk-adjusted mortality for surgery were also examined as a function of individual surgeon mitral case volume. ResultsPropensity-matched patients who underwent MV-repair experienced a significantly lower mortality rate at 4 years (3.5% vs 12.1%, P < .001). Greater-volume surgeons were more likely to perform MV-repairs (92% vs 84%, 74%, and 69% in lower volume quartiles, respectively). No significant differences in mortality were observed among volume quartiles. ConclusionsPatients with chronic severe primary mitral valve regurgitation with preserved ventricular function and no CHF symptoms who underwent MV-repair experienced lower mortality and no different reoperation, CHF, or stroke readmission rates than patients who underwent replacement. Greater-volume surgeons were more likely than their lower volume counterparts to choose mitral repair. Repair should be considered as the surgical option for these patients whenever possible.

A hybrid technique for treatment of commissural primary mitral regurgitation.

MitraClip is an effective transcatheter therapy for mitral regurgitation (MR). However, MitraClip is challenging in commissural MR and the optimal therapeutic approach is unclear. We describe a case series of six consecutive patients with severe commissural primary mitral regurgitation who underwent MitraClip insertion followed by an Amplatzer Vascular Plug (AVP) II occluder between the commissure and the MitraClip. The procedure was successful in all patients. MR was reduced from severe to mild/trivial in 50% and moderate in 50% of cases. On 30-day follow-up, NYHA class had improved from III (6 patients) to I (2 patients), II (2 patients), and III (2 patients). The mean transmitral gradient was 2.5 ± 1.8 mmHg at baseline and 4.8 ± 2.6 mmHg following the procedure. One patient developed hemolysis immediately post procedure. The other five patients remained well during a median follow-up of 20 months (range 5-50 months) with no reported device dislodgement. Elective treatment of severe commissural MR with a laterally or medially placed MitraClip coupled with an AVP II occluder between the clip and the commissure is feasible and safe. This approach may provide a useful management alternative in selected patients.

Acute Effect of Mitral Valve Repair on Mitral Valve Geometry.

The aim of this study was to quantify acute mitral valve (MV) geometry dynamic changes throughout the cardiac cycle using three-dimensional transesophageal echocardiography (3D TEE) in patients undergoing surgical MV repair (MVR) with ring annuloplasty and optional neochord implantation. Twenty-nine patients (63 ± 10 years) with severe primary mitral regurgitation underwent surgical MVR using ring annuloplasty with or without neochord implantation. We recorded 3D TEE data throughout the cardiac cycle before and after MVR. Dynamic changes (4D) in the MV annulus geometry and anatomical MV orifice area (AMVOA) were measured using a novel semiautomated software (Auto Valve, Siemens Healthcare). MVR significantly reduces the anteroposterior diameter by up to 38% at end-systole (36.8-22.7 mm; p < 0.001) and the lateromedial diameter by up to 31% (42.7-30.3 mm; p < 0.001). Moreover, the annular circumference was reduced by up to 31% at end-systole (129.6-87.6 mm, p < 0.001), and the annular area was significantly decreased by up to 52% (12.8-5.7 cm2; p < 0.001). Finally, the AMVOA experienced the largest change, decreasing from 1.1 to 0.2 cm2 during systole (at midsystole; p < 0.001) and from 4.1 to 3.2 cm2 (p < 0.001) during diastole. MVR reduces the annular dimension and the AMVOA, contributing to mitral competency, but the use of annuloplasty rings reduces annular contractility after the procedure. Surgeons can use 4D imaging technology to assess MV function dynamically, detecting the acute morphological changes of the mitral annulus and leaflets before and after the procedure.

6161Reduced myocardial ATP delivery in severe primary mitral regurgitation: a novel marker to guide timing of surgery?

6161Reduced myocardial ATP delivery in severe primary mitral regurgitation: a novel marker to guide timing of surgery?

P1483Left atrial size is a powerful predictor of outcome in severe asymptomatic primary mitral regurgitation

P1483Left atrial size is a powerful predictor of outcome in severe asymptomatic primary mitral regurgitation

Incidence and treatment of severe primary mitral regurgitation in contemporary clinical practice.

Mitral regurgitation (MR) is a common valvular disorder, occurring in up to 10% of the general population. Although surgery is the established treatment for primary MR, many patients do not receive appropriate therapy. The objective of this study was to determine the incidence and treatment pattern of patients with severe MR evaluated at a tertiary medical center and determine factors associated with receiving surgery. All patients with moderate-severe and severe MR undergoing transthoracic echocardiography from 2011 to 2016 were identified. Patients with prior mitral valve surgery were excluded. Treatment recommendations were classified as referral to cardiology, referral to cardiothoracic surgery (CTS), receiving mitral valve surgery or receiving MitraClip. A multivariate logistic regression model was used to evaluate factors associated with referral to CTS or receiving surgery. During the study period, 1918 transthoracic echocardiogram were performed and 412 patients with moderate-severe or severe MR were identified. One hundred sixty-six patients (40%) had primary MR and 246 patients (60%) had secondary MR. For those with primary MR, 75 patients (45%) received treatment (surgery, n = 60 and MitraClip, n = 15) and 91 patients (55%) did not receive treatment. One hundred patients (60%) were referred to CTS and 128 patients (77%) were referred to cardiology. Patients undergoing surgery were younger (62.6 ± 14.2 years vs 72.0 ± 14 years, p < 0.001), with a higher prevalence of heart failure (57% vs 40%, p = 0.044) and a lower prevalence of stroke (3% vs 24%, p < 0.001) and hypertension (54% vs 74%, p = 0.012), compared to patients not undergoing surgery, respectively. Ejection fraction (60.4 ± 10.9% vs 56.3 ± 11.6%, p = 0.034), left ventricular end diastolic diameter (53.2 ± 10.3 mm vs 48.7 ± 10.9 mm, p = 0.040) and effective regurgitant orifice area (0.5 ± 0.4 cm2 vs 0.3 ± 0.1 cm2) were higher in patients undergoing surgery, compared to patients not undergoing surgery, respectively. The most common reason for not receiving surgery was that MR was not addressed by the treating physician and lost to clinical follow-up. Over 50% of patients that did not receive surgery had at least 1 indication based upon current practice guidelines. In contemporary clinical practice, less than half of patients with moderate-severe and severe primary MR received surgery and many were not referred for surgical consultation.

Long-Term Outcome of Active Surveillance in Severe But Asymptomatic Primary Mitral Regurgitation

ObjectivesThis study sought to assess the long-term outcome of active surveillance in these patients. BackgroundThe optimal timing of mitral valve surgery in asymptomatic primary mitral regurgitation (MR) remains controversial. MethodsBetween 1997 and 2015, 280 consecutive patients with severe asymptomatic primary MR were enrolled in our heart valve clinic follow-up program. They were prospectively followed up every 6 months clinical and echocardiographical examinations until surgical criteria were reached. Event-free survival and overall survival as compared with the age- and gender-matched general population were assessed. ResultsDuring a median potential follow-up of 93.4 (quartiles 55.3 to 152.9) months, 161 patients developed an indication for surgery and 13 patients died. Event-free survival rates were 78.0% (95% confidence interval [CI]: 73.2% to 83.2%) at 2 years, 52.2% (95% CI: 46.3% to 59.0%) at 6 years, 35.5% (95% CI: 29.3% to 43.1%) at 10 years, and 18.7% (95% CI: 12.3% to 28.5%) at 15 years. Overall survival rate was 99.6% (95% CI: 98.9% to 100%) at 2 years, 94.6% (95% CI: 91.7% to 97.6%) at 6 years, 85.6% (95% CI: 80.3% to 91.2%) at 10 years, and 74.5% (95% CI: 66.6% to 83.4%) at 15 years. Overall survival of patients managed according to an active surveillance strategy was comparable with the expected cumulative survival and early survival rates were even better in the study population (standardized mortality ratio: 0.667; 95% CI: 0.463 to 0.963; p = 0.013). ConclusionsPatients with severe asymptomatic primary MR may remain free of indications for surgery for extensive periods of time. In such patients, active surveillance performed in experienced centers is associated with a favorable prognosis, resulting in timely referral to surgery, excellent long-term survival, and good surgical outcomes.

Myocardial Strain in Prediction of Outcomes After Surgery for Severe Mitral Regurgitation

ObjectivesWe investigated whether global longitudinal strain (GLS) is a better predictor of clinical events after surgery for mitral regurgitation (MR) than conventional parameters. BackgroundThe optimal timing for surgery is guided by left ventricular (LV) dimension or left ventricular ejection fraction (LVEF), even though normal LVEF can mask depressed LV systolic function in severe mitral MR. MethodsFrom 2006 to 2016, 506 patients (age 58.5 ± 13.7 years, 54.3% male) with severe primary MR who underwent mitral valve surgery were included. We measured GLS and global circumferential strain. Cardiac events included admission for worsening heart failure (HF), reoperation for failure of MV surgery, and cardiac death. ResultsDuring a median follow-up period of 3.5 years, 56 (11.1%) patients died, 41 (8.1%) were hospitalized for HF, and 10 (2.0%) underwent reoperation. In univariate analysis, LVEF, atrial fibrillation, left atrial dimension, age, previous ischemia, concomitant coronary artery bypass graft, and both GLS and global circumferential strain were predictive of cardiac events. On multivariate Cox models, age (hazard ratio [HR]: 1.429, 95% confidence interval [CI]: 1.116 to 1.831; p = 0.005), left atrial dimension (HR: 1.034, 95% CI: 1.006 to 1.063; p = 0.019) and GLS (HR: 1.229, 95% CI: 1.135 to 1.331; p < 0.001) were independent predictors of cardiac events. In subgroup analysis, LV GLS was a significant predictor of cardiac outcome, regardless of the presence of LV dysfunction, the presence of atrial fibrillation, and the type of surgery. Impaired GLS was associated with all-cause mortality (HR: 1.068, 95% CI: 1.003 to 1.136; p = 0.040). ConclusionsGLS appears to be a better predictor of cardiac events all-cause death than conventional parameters. Measuring preoperative GLS is helpful to predict post-operative outcome and determine optimal timing for surgery in patients with severe primary MR.

Good 5-Year Durability of Transapical Beating Heart Off-Pump Mitral Valve Repair With Neochordae

Transapical, beating heart, off-pump implantation of neochordae for repair of mitral valve (MV) prolapse is of increasing interest. The aim of this study was to evaluate long term results for MV repair using the NeoChord system (NeoChord, St. Louis Park, MN). Six patients underwent treatment for severe primary mitral regurgitation (MR) with the NeoChord DS1000 system as part of the initial device safety and feasibility Transapical Artificial Chordae Tendinae (TACT) trial at our institution (University of Leipzig-Heart Center, Leipzig, Germany). The primary pathology in all patients was isolated posterior leaflet prolapse of the P2 or P3 segment, or both. Successful repair resulting in no or trace MR was achieved in 5 of 6 patients by implantation of three neochordae under transesophageal echocardiographic guidance and normal left ventricular loading conditions. One patient underwent intraoperative conversion to an open MV replacement as a result of leaflet injury. The early postoperative course was uneventful in all remaining patients. Two patients had to undergo reoperation for recurrent MR at 3 and 16 months postoperatively. The remaining 3 patients were followed up for a period of 5 years. These patients were free of cardiac symptoms, and transthoracic examination showed trace or mild to moderate MR at 1-, 2-, and 5-year follow-up. A trend toward reverse remodeling of the left ventricle with no increase in mitral annular dilatation over 5 years was observed. In select patients, MV repair using the NeoChord system results in very good long-term results without recurrent prolapse, MR, or annular dilatation.

Predictors of post-operative cardiovascular events, focused on atrial fibrillation, after valve surgery for primary mitral regurgitation.

Primary mitral regurgitation (PMR) can be considered as a heterogeneous clinical disease. The optimal timing of valve surgery for severe PMR remains unknown. To determine whether unbiased clustering analysis using dense phenotypic data (phenomapping) could identify phenotypically distinct PMR categories of patients. One hundred and twenty-two patients who underwent surgery were analysed, excluding patients with pre-operative permanent atrial fibrillation (AF), were prospectively included before surgery. They were given an extensive echocardiographic evaluation before surgery, and clinical data were collected. These phenotypic variables were grouped in clusters using hierarchical clustering analysis. Then, different groups were created using a dedicated phenomapping algorithm. Post-operative outcomes were compared between the groups. The primary endpoint was post-operative cardiovascular events (PCE), defined as a composite of: deaths, AF, stroke, and rehospitalization. The secondary endpoint was post-operative AF. Data from three phenogroups with different characteristics and prognoses were identified. Phenogroup-1 (67 patients) was the reference group. Phenogroup-2 (33 patients) included intermediate-risk male and smoker patients with heart remodelling. Phenogroup-3 (22 patients) included older female patients with comorbidities (chronic renal failure, paroxysmal AF) and diastolic dysfunction. They had a higher risk of developing both PCE [(hazard ratio) HR = 3.57(1.72-7.44), P < 0.001] and post-operative AF [HR = 4.75(2.03-11.10), P < 0.001]. Pre-operative paroxysmal AF was identified as an independent risk factor for PCE. Classification of PMR can be improved using statistical learning algorithms to define therapeutically homogeneous patient subclasses. High-risk patients can be identified, and these patients should be carefully monitored and may even be treated earlier.

Left ventricular remodelling in chronic primary mitral regurgitation: implications for medical therapy.

SummarySurgical repair or replacement of the mitral valve is currently the only recommended therapy for severe primary mitral regurgitation. The chronic elevation of wall stress caused by the resulting volume overload leads to structural remodelling of the muscular, vascular and extracellular matrix components of the myocardium. These changes are initially compensatory but in the long term have detrimental effects, which ultimately result in heart failure. Understanding the changes that occur in the myocardium due to volume overload at the molecular and cellular level may lead to medical interventions, which potentially could delay or prevent the adverse left ventricular remodelling associated with primary mitral regurgitation. The pathophysiological changes involved in left ventricular remodelling in response to chronic primary mitral regurgitation and the evidence for potential medical therapy, in particular beta–adrenergic blockers, are the focus of this review.

Hemodynamic Characteristics in Significant Symptomatic and Asymptomatic Primary Mitral Valve Regurgitation at Rest and During Exercise.

In severe asymptomatic primary mitral valve regurgitation without risk factors, surgery strategy is controversial. We sought to clarify whether being symptomatic corresponds to the hemodynamic burden and reduced exercise capacity. A better understanding of this may contribute to optimize timing of surgery. Subjects with asymptomatic (New York Heart Association functional class I, n=29) or symptomatic (New York Heart Association functional class II and III, n=28) significant primary mitral valve regurgitation (effective regurgitant orifice, ≥0.30 cm2; left ventricular ejection fraction, >60%) were included. Right heart catheterization during rest and exercise, echocardiography, magnetic resonance imaging, and peak oxygen consumption test was performed. Symptomatic subjects had significantly higher pulmonary capillary wedge pressure at rest (14±4 versus 11±3 mm Hg; P=0.003) and at maximal exercise (30±6 versus 25±7 mm Hg; P=0.02) and higher mean pulmonary artery pressure (PAP) at rest (22±7 versus 18±4 mm Hg; P=0.005) and maximal exercise (46±8 versus 39±7 mm Hg; P=0.005) than asymptomatic subjects. Among asymptomatic subjects with normal resting value, exercise testing revealed a systolic PAP >60 mm Hg in 34%. Also the reverse response with minimal increase in pulmonary capillary wedge pressure and mean PAP during exercise was seen, especially in asymptomatic subjects. Among symptomatic subjects, we found a significant inverse correlation between resting mean PAP and left ventricular ejection fraction (r=-0.52; P=0.02) and right ventricular ejection fraction (r=-0.67; P<0.01). Peak oxygen consumption was equal and normal in both groups and correlated with left ventricular stroke volume but not with pulmonary capillary wedge pressure. Symptoms in patients with severe mitral valve regurgitation relate to congestion (pulmonary capillary wedge pressure and PAP), but not to peak oxygen consumption, which is determined by forward left ventricular stroke volume. Exercise testing reveals a higher mitral valve regurgitation burden in apparently asymptomatic patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02961647.