Tribouilloy, Christophe

Abstract Aims In patients with degenerative mitral regurgitation (DMR), left ventricular (LV) dysfunction is associated with increased risk of heart failure and excess mortality. LV end‐systolic diameter (LVESD) is an established trigger for intervention, yet recommended LVESD thresholds apply poorly to patients with small body size. Whether LV normalization to body surface area (BSA) may be used as a trigger for DMR correction is unknown. We examined the link between LVESD index (LVESDi) and outcome in DMR to identify appropriate thresholds for excess mortality. Methods and results This study focuses on 2753 consecutive patients with DMR due to flail leaflets diagnosed in tertiary centres from Europe and the United States, with prospective echocardiographic measurement of LVESD and BSA and long‐term follow‐up. The primary endpoint was mortality after diagnosis under conservative management. Secondary endpoints were mortality under conservative and surgical management and postoperative mortality of patients who underwent surgery. The optimal LVESDi cut‐off for mortality prediction was 20 mm/m 2 . Irrespective of management type, 10‐year survival was lower with LVESDi ≥20 mm/m 2 than with LVESDi <20 mm/m 2 (both p < 0.001). After covariate adjustment, LVESDi ≥20 mm/m 2 was independently predictive of mortality under conservative management (adjusted hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.15–1.75), and with conservative and surgical management (adjusted HR 1.34, 95% CI 1.17–1.54). LVESDi remained associated with poorer postoperative outcome in patients who underwent intervention. LVESDi showed higher incremental predictive value over the baseline model compared to LVESD. The association between LVESDi ≥20 mm/m 2 and outcome was consistent in subgroups of patients with DMR. Conclusions In severe DMR due to flail leaflets, LVESDi is a marker of risk additive and incremental to LVESD. Its use in clinical practice should lead to earlier referral to mitral valve surgery and improved long‐term outcome.

Background: Mitral valve (MV) repair is preferred over replacement in clinical guidelines and is an important determinant of the indication for surgery in degenerative mitral regurgitation. However, the level of evidence supporting current recommendations is low, and recent data cast doubts on its validity in the current era. Accordingly, the aim of the present study was to analyze very long-term outcome after MV repair and replacement for degenerative mitral regurgitation with a flail leaflet. Methods: MIDA (Mitral Regurgitation International Database) is a multicenter registry enrolling patients with degenerative mitral regurgitation with a flail leaflet in 6 tertiary European and US centers. We analyzed the outcome after MV repair (n=1709) and replacement (n=213) overall, by propensity score matching, and by inverse probability-of-treatment weighting. Results: At baseline, patients undergoing MV repair were younger, had more comorbidities, and were more likely to present with a posterior leaflet prolapse than those undergoing MV replacement. After propensity score matching and inverse probability-of-treatment weighting, the 2 treatments groups were balanced, and absolute standardized differences were usually <10%, indicating adequate match. Operative mortality (defined as a death occurring within 30 days from surgery or during the same hospitalization) was lower after MV repair than after replacement in both the entire population (1.3% versus 4.7%; P <0.001) and the propensity-matched population (0.2% versus 4.4%; P <0.001). During a mean follow-up of 9.2 years, 552 deaths were observed, of which 207 were of cardiovascular origin. Twenty-year survival was better after MV repair than after MV replacement in both the entire population (46% versus 23%; P <0.001) and the matched population (41% versus 24%; P <0.001). Similar superiority of MV repair was obtained in patient subsets on the basis of age, sex, or any stratification criteria (all P <0.001). MV repair was also associated with reduced incidence of reoperations and valve-related complications. Conclusions: Among patients with degenerative mitral regurgitation with a flail leaflet referred to mitral surgery, MV repair was associated with lower operative mortality, better long-term survival, and fewer valve-related complications compared with MV replacement.

Background— Ejection fraction (EF) as a marker of left ventricular (LV) dysfunction and the appropriate thresholds for diagnosing severe or mild/moderate LV dysfunction in mitral regurgitation are doubted and poorly followed in clinical practice. We aimed at assessing the role of EF in a large registry of organic mitral regurgitation to objectively establish thresholds for various degrees of LV dysfunction and to analyze whether mitral surgery remains beneficial in those subsets of patients. Methods and Results— We investigated the relation between EF and mortality in 1875 patients with mitral regurgitation due to flail leaflets in sinus rhythm (65±13 years; median EF, 66% [60%–71%]) enrolled in the Mitral Regurgitation International Database (MIDA) registry. With EF <60%, mortality after diagnosis increased precipitously under medical management (adjusted hazard ratio [HR], 1.59 [1.19–2.12]) and during the entire follow-up (adjusted HR, 1.51 [1.22–1.87]). Severe LV dysfunction, if defined by EF <30%, would affect a minuscule number of patients (0.3%). Conversely, EF <45% was more frequent (2.9%) and was associated with considerable mortality under medical management (adjusted HR, 2.43 [1.50–3.95]) and during the entire follow-up (adjusted HR, 2.46 [1.67–3.61]). The group with EF of 45% to 60% represented a large proportion of patients (23%), exhibited rarely overt symptoms, and had higher mortality compared with EF >60%. Above 60%, no EF threshold further determined survival. The benefit of surgery remained considerable in the groups with EF <45% (adjusted HR, 0.28 [0.17–0.56]) and with EF of 45% to 60% (adjusted HR, 0.34 [0.21–0.64]). Conclusions— EF is valuable in defining presence and severity of LV dysfunction in organic mitral regurgitation. Patients with EF <45% have severe LV dysfunction, catastrophic outcome under medical management, and should not be denied surgery. Although there is no survival gain with EF ranges >60%, with EF dropping <60%, mortality increases precipitously and prompt surgical referral is critical to outcome.

Background —Functional mitral regurgitation (FMR) occurs with a structurally normal valve as a complication of systolic left ventricular dysfunction (LVD). Determinants of degree of FMR are poorly defined; thus, mechanistic therapeutic approaches to FMR are hindered. Methods and Results —In a prospective study of 21 control subjects and 128 patients with LVD (defined as ejection fraction <50%, mean 31±9%) in sinus rhythm, we quantified simultaneously by echocardiography the effective regurgitant orifice (ERO) of FMR by using 2 methods: mitral deformation (valve and annulus) and left ventricular (LV) global (volumes, stress, function, and sphericity) and local (papillary muscle displacements and regional wall motion index) remodeling. A wide range of ERO (15±14 mm 2 , 0 to 87 mm 2 ) was observed, unrelated to ejection fraction ( P =0.32). The major determinant of ERO was mitral deformation, ie, systolic valvular tenting and annular contraction in univariate ( r =0.74 and r =−0.61, respectively; both P <0.0001) and multivariate (both P <0.0001) analyses, independent of global LV remodeling. Systolic valvular tenting was strongly determined by local LV alterations, particularly apical ( r =0.75) and posterior ( r =0.70) displacement of papillary muscle, with confirmation in multivariate analysis (both P <0.0001), independent of LV volumes, function, and sphericity. Conclusions —The presence and degree of FMR complicating LVD are unrelated to the severity of LVD. Local LV remodeling (apical and posterior displacement of papillary muscles) leads to excess valvular tenting independent of global LV remodeling. In turn, excess tenting and loss of systolic annular contraction are associated with larger EROs. These determinants of FMR warrant consideration for specific approaches to the treatment of FMR complicating LVD.

Background— Left atrium (LA) enlargement is common in organic mitral regurgitation (MR) and is an emerging prognostic indicator. However, outcome implications of LA enlargement have not been analyzed in the context of routine clinical practice and in a multicenter study. Methods and Results— The Mitral Regurgitation International DAtabase (MIDA) registry enrolls patients with organic MR due to flail leaflets, diagnosed in routine clinical practice, in 5 US and European centers. We investigated the relation between LA diameter and mortality under medical treatment and after mitral surgery in 788 patients in sinus rhythm (64±12 years; median LA, 48 [43 to 52] mm). LA diameter was independently associated with survival after diagnosis (hazard ratio, 1.08 [1.04 to 1.12] per 1 mm increment). Compared with patients with LA <55 mm, those with LA ≥55 mm had lower 8-year overall survival ( P <0.001). LA ≥55 mm independently predicted overall mortality (hazard ratio, 3.67 [1.95 to 6.88]) and cardiac mortality (hazard ratio, 3.74 [1.72 to 8.13]) under medical treatment. The association of LA ≥55 mm and mortality was consistent in subgroups. Similar excess mortality associated with LA ≥55 mm was observed in asymptomatic and symptomatic patients ( P for interaction, 0.77). In patients who underwent mitral surgery, LA ≥55 mm had no impact on postoperative outcome ( P >0.20). Mitral surgery was associated with greater survival benefit in patients with LA ≥55 mm compared with LA <55 mm ( P for interaction, 0.008). Conclusions— In MR caused by flail leaflets, LA diameter ≥55 mm is associated with increased mortality under medical treatment, independent of the presence of symptoms or left ventricular dysfunction.

Background— Respiratory dependence of tricuspid regurgitation (TR), a long-held concept suggested by murmur variation, remains unproven and of unclear mechanisms. Methods and Results— In 41 patients with mild or greater TR (median age, 67 years), we performed triple Doppler echocardiographic quantification (TR severity, right ventricular, and right atrial quantification) with simultaneous respirometer recording of respiratory phases. Expiration to inspiration changes (median) affected TR peak velocity (−40 cm/s; 25th to 75th percentile, −60 to −30 cm/s), duration (−12 milliseconds; 25th to 75th percentile, −45 to 2 milliseconds), and time-velocity integral (−17 cm; 25th to 75th percentile, −23.4 to −10 cm; all P <0.001), consistent with decreased TR driving force. Nevertheless, inspiratory TR augmentation was demonstrated by increased effective regurgitant orifice (0.21 cm 2 ; 25th to 75th percentile, 0.09 to 0.34 cm 2 ) and volume (18 mL per beat; 25th to 75th percentile, 10 to 25 mL per beat; all P <0.001) infrequently detected clinically (2 of 41, 5). As a result of reduced TR driving force, regurgitant volume increased less than effective regurgitant orifice (120 [25th to 75th percentile, 78.6 to 169] versus 169 [ 25th to 75th percentile, 12.9 to 226.1]; P <0.001). During inspiration, right ventricular area increased (diastolic, 27.8 [25th to 75th percentile, 22.6 to 36.3] versus 26.5 [21.1 to 31.9]; P <0.0001) with widening of right ventricular shape (length-to-width ratio, 1.6 [ 25th to 75th percentile, 1.37 to 1.95] versus 1.7 [1.46 to 2.1]; P <0.0001), increased systolic annular diameter ( P =0.003), valve tenting height ( P <0.0001) and area ( P <0.0001), and reduced valvular-to-annular ratio ( P =0.006). Effective regurgitant orifice during inspiration was independently determined by inspiratory valvular-to-annular ratio ( P =0.026) and inspiratory change in right ventricular length-to-width ratio ( P =0.008) and valve tenting area ( P =0.015). Conclusions— TR is dynamic with almost universal respiratory changes of large magnitude and complex pathophysiology. During inspiration, a large increase in effective regurgitant orifice causes, despite a decline in regurgitant gradient, a notable increase in regurgitant volume. Effective regurgitant orifice changes are independently linked to inspiratory annular enlargement (decreased valvular coverage) and to inspiratory right ventricular shape widening with increased valvular tenting. These novel physiological insights into TR respiratory dependence underscore right-side heart plasticity and are important for clinical TR severity evaluation.