Mitral Regurgitation International Database Research Articles

Degenerative mitral regurgitation due to flail leaflet: sex-related differences in presentation, management, and outcomes.

Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes. In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up. At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27-1.65), P < .001] but was higher in females [SMR 2.00 (1.67-2.38), P < .001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04-1.61), P = .02], cardiovascular mortality [adjusted HR 1.58 (1.14-2.18), P = .007], and heart failure [adjusted HR 1.36 (1.02-1.81), P = .04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P < .001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥ .09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16-1.47), P < .001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85-0.99), P = .036]. Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management.

Data-driven mortality risk prediction of severe degenerative mitral regurgitation patients undergoing mitral valve surgery.

The outcomes of mitral valve replacement/repair (MVR) in severe degenerative mitral regurgitation (MR) patients depend on various risk factors. We aimed to develop a risk prediction model for post-MVR mortality in severe degenerative MR patients using machine learning. Consecutive severe degenerative MR patients undergoing MVR were analysed (n = 1521; 70% training/30% test sets). A random survival forest (RSF) model was constructed, with 3-year post-MVR all-cause mortality as the outcome. Partial dependency plots were used to define the thresholds of each risk factor. A simple scoring system (MVR-score) was developed to stratify post-MVR mortality risk. At 3 years following MVR, 90 patients (5.9%) died in the entire cohort (59 and 31 deaths in the training and test sets). The most important predictors of mortality in order of importance were age, haemoglobin, valve replacement, glomerular filtration rate, left atrial dimension, and left ventricular (LV) end-systolic diameter. The final RSF model with these six variables demonstrated high predictive performance in the test set (3-year C-index 0.880, 95% confidence interval 0.834-0.925), with mortality risk increased strongly with left atrial dimension >55 mm, and LV end-systolic diameter >45 mm. MVR-score demonstrated effective risk stratification and had significantly higher predictability compared to the modified Mitral Regurgitation International Database score (3-year C-index 0.803 vs. 0.750, P = 0.034). A data-driven machine learning model provided accurate post-MVR mortality prediction in severe degenerative MR patients. The outcome following MVR in severe degenerative MR patients is governed by both clinical and echocardiographic factors.

The MIDA-Q Mortality Risk Score: A Quantitative Prognostic Tool for the Mitral Valve Prolapse Spectrum.

Mitral valve prolapse (MVP) is responsible for a considerable disease burden but is widely heterogeneous. The lack of a comprehensive prognostic instrument covering the entire MVP spectrum, encompassing the quantified consequent degenerative mitral regurgitation (DMR), hinders clinical management and therapeutic trials. The new Mitral Regurgitation International Database Quantitative (MIDA-Q) registry enrolled 8187 consecutive patients (ages 63±16 years, 47% women, follow-up 5.5±3.3 years) first diagnosed with isolated MVP, without or with DMR quantified prospectively (measuring effective regurgitant orifice [ERO] and regurgitant volume) in routine practice of 5 tertiary care centers from North America, Europe, and the Middle East. The MIDA-Q score ranges from 0 to 15 by accumulating guideline-based risk factors and DMR severity. Long-term survival under medical management was the primary outcome end point. MVP was associated with DMR absent/mild (ERO <20 mm2) in 50%, moderate (ERO 20-40 mm2) in 25%, and severe or higher (ERO ≥40 mm2) in 25%, with mean ERO 24±24 mm2, regurgitant volume 37±35 mL. Median MIDA-Q score was 4 with a wide distribution (10%-90% range, 0-9). MIDA-Q score was higher in patients with EuroScore II ≥1% versus <1% (median, 7 versus 3; P < 0.0001) but with wide overlap (10%-90% range, 4-11 versus 0-7) and mediocre correlation (R2 0.18). Five-year survival under medical management was strongly associated with MIDA-Q score, 97±1% with score 0, 95±1% with score 1 to 2, 82±1% with score 3 to 4, 67±1% with score 5 to 6, 60±1% with score 7 to 8, 44±1% with score 9 to 10, 35±1% with score 11 to 12, and 5±4% with MIDA-Q score ≥13, with hazard ratio 1.31 [1.29-1.33] per 1-point increment. Excess mortality with higher MIDA-Q scores persisted after adjustment for age, sex, and EuroScore II (adjusted hazard ratio, 1.13 [1.11-1.15] per 1-point increment). Subgroup analysis showed persistent association of MIDA-Q score with mortality in all possible subsets, in particular, with EuroScore II<1% (hazard ratio, 1.08 [1.02-1.14]) or ≥1% (hazard ratio, 1.11 [1.08-1.13]) and with no/mild DMR (hazard ratio, 1.14 [1.10-1.19]) or moderate/severe DMR (hazard ratio, 1.13 [1.10-1.16], all per 1-point increment with P<0.0001). Nested-model and bootstrapping analyses demonstrated incremental prognostic power of MIDA-Q score (all P<0.0001). This large, international cohort of isolated MVP, with prospective DMR quantification in routine practice, demonstrates the wide range of risk factor accumulation and considerable heterogeneity of outcomes after MVP diagnosis. The MIDA-Q score is strongly, independently, and incrementally associated with long-term survival after MVP diagnosis, irrespective of presentation, and is therefore a crucial prognostic instrument for risk stratification, clinical trials, and management of patients diagnosed with all forms of MVP.

Long-term outcomes in distinct phenogroups of patients with primary mitral regurgitation undergoing valve surgery

ObjectivesPatients with mitral regurgitation (MR) may be heterogeneous with different risk profiles. We aimed to identify distinct phenogroups of patients with severe primary MR and investigate their long-term prognosis after...

The MIDA quantitative mortality risk score: Prognostic model in floppy mitral valves

The Mitral-Regurgitation-International-Database (MIDA) score is a validated tool for Degenerative-Mitral-Regurgitation (DMR) management. However, whether this score complemented with DMR quantitation is applicable and incremental over the entire span of Floppy Mitral Valves (FMV), and DMR severity remains unsubstantiated. The MIDA-Quantitative (MIDA-Q) unprecedented registries include 8187 consecutive patients (age 64 ± 17 years, 45% women, follow-up 5.5 ± 3.4 years) with isolated FMV diagnosed at tertiary (European/North-American/Middle East) centers in which DMR quantitative grading was consistently and prospectively performed. The MIDA-Q Score ranged from 0 to 15 depending on accumulating risk factors. Long-term survival overall, under medical management and post-mitral surgery was analyzed. By quantitative grading, MR was no/trivial in 1938 (24%), mild in 1423 (17%), moderate in 2027 (25%) and severe in 2799 (34%), with ERO 0.24 ± 24 cm 2 , RVol 37 ± 35 mL and with posterior leaflet prolapse in 49%. MIDA-Q Scores stratified in 8 categories were 0 (score 0, n = 851), 1 (score 1–2, n = 1301), 2 (score 3–4, n = 2043), 3 (score 5–6, n = 1581), 4 (score 7–8, n = 1273), 5 (score 9–10, n = 718), 6 (score 11–12, n = 331) and 7 (score 13–15, n = 89). In the whole MIDA-Q population ( n = 8187 patients), 5-year survival under medical management with Scores categories 0-1, 2–4, and 5–7 was 96 ± 1%, 73 ± 1%, and 61 ± 3% respectively ( P < 0.0001). After mitral surgery, 1-year mortality with Scores categories 0–1, 2–4, and 5–7 was 0%, 1%, and 6% respectively and 5-year post-operative survival was 99 ± 1%, 94 ± 1%, and 82 ± 2% (all P < 0.0001). In nested models including age, sex and EuroScoreII, the MIDA Score was incrementally, and the MIDA-Q Score further incrementally prognostic for long-term survival ( P < 0.001) ( Fig. 1 ). This very large international cohort demonstrates the strong, independent and incremental predictive power of the MIDA-Q Score for survival after diagnosis of FMV.

The MIDA quantitative mortality risk score: prognostic model in floppy mitral valves

Abstract Background The Mitral Regurgitation International Database (MIDA) score is a validated tool for Degenerative Mitral Regurgitation (DMR) management, being able to position a given patient within a continuous spectrum of short and long term mortality. However, whether this score may be applicable and incremental in the entire span of Floppy Mitral Valves (FMV), regardless of DMR severity, remains unsubstantiated. Methods The MIDA-Quantitative (MIDA-Q) unprecedented registries include 8187 consecutive patients (age 64±17 years, 45% women, follow-up 5.5±3.4 years) with isolated degenerative mitral valve disease diagnosed at tertiary (European/ North-American/ Middle Eastern) centers in whom DMR severity used both integrative and quantitative grading. The MIDA-Q Score ranged from 0 to 15 depending on accumulating risk factors. Long-term survival overall, under medical management and post-mitral surgery was analysed. Results By quantitative grading, MR was no/trivial in 1938 (24%), mild in 1423 (17%), moderate in 2027 (25%) and severe in 2799 (34%), with ERO 0.24±24cm2, RVol 37±35mL, and posterior leaflet prolapse in 49%. MIDA-Q Scores stratified in 8 categories were 0 (score 0, n=851), 1 (score 1–2, n=1301), 2 (score 3–4, n=2043), 3 (score 5–6, n=1581), 4 (score 7–8, n=1273), 5 (score 9–10, n=718), 6 (score 11–12, n=331) and 7 (score 13–15, n=89). In the whole MIDA-Q population (n=8187 patients), 5-year survival under medical management with Scores categories 0–1, 2–4, and 5–7 was 96±1%, 73±1%, and 61±3% respectively (P&amp;lt;0.0001). Five-year mortality ranged from 3% with MIDA Q-score 0 to 95% with MIDA Q-score 13–15 (P&amp;lt;0.0001). After mitral surgery, 1-year mortality with Scores categories 0–1, 2–4, and 5–7 was 0%, 1%, and 6% respectively and 5-year post-operative survival was 99±1%, 94±1%, and 82±2% (all P&amp;lt;0.0001). In models including age, sex and all guideline-provided prognostic markers, the EuroScoreII and the MIDA Score without DMR severity, the MIDA-Q Score provided incremental prognostic information (P&amp;lt;0.001). Conclusion This unheard international cohort of patients with FMV and prospective mitral severity quantitative grading, enables for the first time the calculation of a MIDA-Q Score, highly determinant of survival after diagnosis of FMV with any degree of DMR, that may be very useful for mitral valve prolapse management. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mayo Fundation Figure 1

Mitral Regurgitation International Database (MIDA) Score Predicts Outcome in Patients With Heart Failure Undergoing Transcatheter Edge‐to‐Edge Mitral Valve Repair

BackgroundOptimizing risk stratification in patients undergoing transcatheter mitral valve repair is an ongoing challenge. The Mitral Regurgitation International Database (MIDA) score represents a user‐friendly mortality risk stratification tool that is validated on a large‐scale registry of patients with degenerative mitral regurgitation (MR). We here assessed the potential benefit of the MIDA risk score for patients with functional or degenerative MR undergoing transcatheter mitral valve repair.Methods and ResultsIn total, 680 patients undergoing MitraClip implantation were stratified according to MIDA score tertiles into a low (0–7), intermediate (8–9), and a high (10–12) MIDA score group. MR was assessed in follow‐up echocardiograms in 416 patients at 323±169 days after transcatheter mitral valve repair. During 2‐year follow‐up, 8.2% (15/182) of patients with low, 21.3% (64/300) with intermediate, and 26.3% (52/198) with high MIDA score died (log‐rank test P<0.001). Hazard of all‐cause mortality increased by 13% (95% CI, 3%–25%) with every additional point of the MIDA score. Subanalysis of 431 patients with functional MR showed similar results. Furthermore, rates of a combined end point of mortality and hospitalization for heart failure were higher with increasing MIDA score (30% [54/182], 38% [113/300] and 48% [94/198], respectively, log‐rank test P=0.001). Frequency of residual MR ≥II at follow‐up increased with increasing MIDA score group (33%, 44%, and 59%, respectively, P<0.001).ConclusionsThe MIDA mortality risk score maintains its predictive utility in patients undergoing transcatheter mitral valve repair, regardless of MR cause. Moreover, it was predictive of worse event‐free survival regarding a combined end point of mortality and hospitalization for heart failure, and was associated with postprocedural residual MR ≥II and MR recurrence.

Long-Term Implications of Atrial Fibrillation in Patients With Degenerative Mitral Regurgitation

BackgroundScientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery. ObjectivesThis study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term. MethodsPatients were enrolled in the MIDA (Mitral Regurgitation International Database) registry, which reported the consecutive, multicenter, international experience with DMR due to flail leaflets echocardiographically diagnosed. ResultsAmong 2,425 patients (age 67 ± 13 years; 71% male, 67% asymptomatic, ejection fraction 64 ± 10%), 1,646 presented at diagnosis with sinus rhythm (SR), 317 with paroxysmal AD, and 462 with persistent AF. Underlying clinical/instrumental characteristics progressively worsened from SR to paroxysmal to persistent AF. During follow-up, paroxysmal and persistent AF were associated with excess mortality (10-year survival in SR and in paroxysmal and persistent AF was 74 ± 1%, 59 ± 3%, and 46 ± 2%, respectively; p < 0.0001), that persisted 20 years post-diagnosis and independently of all baseline characteristics (p values <0.0001). Surgery (n = 1,889, repair 88%) was associated with better survival versus medical management, regardless of all baseline characteristics and rhythm (adjusted hazard ratio: 0.26; 95% confidence interval: 0.23 to 0.30; p < 0.0001) but post-surgical outcome remained affected by AF (10-year post-surgical survival in SR and in paroxysmal and persistent AF was 82 ± 1%, 70 ± 4%, and 57 ± 3%, respectively; p < 0.0001). ConclusionsAF is a frequent occurrence at DMR diagnosis. Although AF is associated with older age and more severe presentation of DMR, it is independently associated with excess mortality long-term after diagnosis. Surgery is followed by improved survival in each cardiac rhythm subset, but persistence of excess risk is observed for each type of AF. Our study indicates that detection of AF, even paroxysmal, should trigger prompt consideration for surgery.

The MIDA Mortality Risk Score: development and external validation of a prognostic model for early and late death in degenerative mitral regurgitation.

In degenerative mitral regurgitation (DMR), lack of mortality scores predicting death favours misperception of individual patients' risk and inappropriate decision-making. The Mitral Regurgitation International Database (MIDA) registries include 3666 patients (age 66 ± 14 years; 70% males; follow-up 7.8 ± 5.0 years) with pure, isolated, DMR consecutively diagnosed by echocardiography at tertiary (European/North/South-American) centres. The MIDA Score was derived from the MIDA-Flail-Registry (2472 patients with DMR and flail leaflet-Derivation Cohort) by weighting all guideline-provided prognostic markers, and externally validated in the MIDA-BNP-Registry (1194 patients with DMR and flail leaflet/prolapse-Validation Cohort). The MIDA Score ranged from 0 to 12 depending on accumulating risk factors. In predicting total mortality post-diagnosis, the MIDA Score showed excellent concordance both in Derivation Cohort (c = 0.78) and Validation Cohort (c = 0.81). In the whole MIDA population (n = 3666 patients), 1-year mortality with Scores 0, 7-8, and 11-12 was 0.4, 17, and 48% under medical management and 1, 7, and 14% after surgery, respectively (P < 0.001). Five-year survival with Scores 0, 7-8, and 11-12 was 98 ± 1, 57 ± 4, and 21 ± 10% under medical management and 99 ± 1, 82 ± 2, and 57 ± 9% after surgery (P < 0.001). In models including all guideline-provided prognostic markers and the EuroScoreII, the MIDA Score provided incremental prognostic information (P ≤ 0.002). The MIDA Score may represent an innovative tool for DMR management, being able to position a given patient within a continuous spectrum of short- and long-term mortality risk, either under medical or surgical management. This innovative prognostic indicator may provide a specific framework for future clinical trials aiming to compare new technologies for DMR treatment in homogeneous risk categories of patients.

Twenty-Year Outcome After Mitral Repair Versus Replacement for Severe Degenerative Mitral Regurgitation: Analysis of a Large, Prospective, Multicenter, International Registry.

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. 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. 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. 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.

0414 : Very long term survival after mitral repair vs replacement. A propensity score analysis of a large, prospective, multicenter international registry

Despite the absence of randomized studies comparing mitral valve (MV) repair and replacement, international guidelines strongly recommend MV repair as the optimal surgical treatment for severe degenerative mitral regurgitation (dMR). Yet, the level of evidence supporting these recommendations is low, owing to the lack of available clinical trial data. In this context, analysis of large multicenter registries becomes critical. To compare very long-term survival among patients (pts) undergoing MV repair versus replacement for the treatment of severe dMR using the technique of propensity score (PS) matching to reduce bias in nonrandomized cohorts. The Mitral Regurgitation International DAtabase (MIDA) is a prospective multicenter registry that includes 2,569 consecutive pts with dMR, who were recruited in 6 tertiary centers (France, Italy, Belgium, and the United States) between 1980 and 2005. Among these, we identified 1,922 pts who underwent mitral surgery, including 1,709MV repairs and 213MV replacements. We compared operative mortality and overall survival in both the entire study population and in 615 PS-matched (2:1) pts. Operative mortality was lower after MV repair than after MV replacement, both in the entire population (2 vs 7%; p=0.001) and in the PSmatched pts (4 vs 8%; p=0.04). Similarly, 20-year survival was better after MV repair than after MV replacement, both in the entire population (46% [(95% CI, 39%-52%] vs 23% [95% CI, 14%-32%], p<0.001) and in the PSmatched pts (41% [95% CI, 28%-54%] vs 24% [95% CI, 14%-33%], p<0.001). Similar results were obtained in pts aged < 65 years (p<0.005), 65- 74 years (p<0.001) and ε75 years (p<0.001). Among registry pts with dMR, performance of MV repair resulted in lower operative mortality and greater long-term survival compared to MV replacement, thus supporting current international recommendations.

Long-Term Mortality Associated With Left Ventricular Dysfunction in Mitral Regurgitation Due to Flail Leaflets

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 &lt;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 &lt;30%, would affect a minuscule number of patients (0.3%). Conversely, EF &lt;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 &gt;60%. Above 60%, no EF threshold further determined survival. The benefit of surgery remained considerable in the groups with EF &lt;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 &lt;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 &gt;60%, with EF dropping &lt;60%, mortality increases precipitously and prompt surgical referral is critical to outcome.

Left Ventricular Ejection Fraction in Mitral Regurgitation Because of Flail Leaflet

It has long been understood that left ventricular ejection fraction (LVEF) is a poor measure of LV systolic function because of load dependence, measurement error, and observer variability. In addition, LVEF, which is calculated from end-diastolic and end-systolic chamber volumes, is really a measure of chamber function not myocardial function. These issues are particularly problematic in mitral regurgitation (MR), where favorable loading conditions can preserve LVEF even when cardiomyocytes demonstrate loss of contractile elements and abnormal mitochondria.1 More sophisticated measures of LV systolic function, such as end-systolic elastance2 and arterial-elastance coupling,3 are of value in MR but are complicated and time-consuming and have not been adopted into clinical practice. Despite its flaws, LVEF remains important in MR because it is widely available and easy to measure. Both the American4 and European5 guidelines indicate that asymptomatic patients should be considered for mitral valve surgery before LVEF falls <60%, particularly when the anatomy is suitable for mitral valve repair. In addition, guidelines suggest that once LVEF falls <30%, the risks of mitral valve surgery might outweigh its benefits. These guidelines are based on expert opinion (Level of Evidence C) because there are limited data to support specific LVEF cutoff values in MR. Article see p 363 In this issue of Circulation: Cardiovascular Imaging, Tribouilloy et al6 report the relation of LVEF to outcomes in a large series of 1875 patients with MR because of flail leaflet in the Mitral Regurgitation International Database (MIDA) registry. Flail leaflet is a common manifestation of degenerative MR, is a known predictor of outcome,7 and usually is associated with severe MR.8 Only patients in sinus rhythm at the time of index echocardiography …

Association Between Early Surgical Intervention vs Watchful Waiting and Outcomes for Mitral Regurgitation Due to Flail Mitral Valve Leaflets

The optimal management of severe mitral valve regurgitation in patients without class I triggers (heart failure symptoms or left ventricular dysfunction) remains controversial in part due to the poorly defined long-term consequences of current management strategies. In the absence of clinical trial data, analysis of large multicenter registries is critical. To ascertain the comparative effectiveness of initial medical management (nonsurgical observation) vs early mitral valve surgery following the diagnosis of mitral regurgitation due to flail leaflets. The Mitral Regurgitation International Database (MIDA) registry includes 2097 consecutive patients with flail mitral valve regurgitation (1980-2004) receiving routine cardiac care from 6 tertiary centers (France, Italy, Belgium, and the United States). Mean follow-up was 10.3 years and was 98% complete. Of 1021 patients with mitral regurgitation without the American College of Cardiology (ACC) and the American Heart Association (AHA) guideline class I triggers, 575 patients were initially medically managed and 446 underwent mitral valve surgery within 3 months following detection. Association between treatment strategy and survival, heart failure, and new-onset atrial fibrillation. There was no significant difference in early mortality (1.1% for early surgery vs 0.5% for medical management, P=.28) and new-onset heart failure rates (0.9% for early surgery vs 0.9% for medical management, P=.96) between treatment strategies at 3 months. In contrast, long-term survival rates were higher for patients with early surgery (86% vs 69% at 10 years, P < .001), which was confirmed in adjusted models (hazard ratio [HR], 0.55 [95% CI, 0.41-0.72], P < .001), a propensity-matched cohort (32 variables; HR, 0.52 [95% CI, 0.35-0.79], P = .002), and an inverse probability-weighted analysis (HR, 0.66 [95% CI, 0.52-0.83], P < .001), associated with a 5-year reduction in mortality of 52.6% (P < .001). Similar results were observed in relative reduction in mortality following early surgery in the subset with class II triggers (59.3 after 5 years, P = .002). Long-term heart failure risk was also lower with early surgery (7% vs 23% at 10 years, P < .001), which was confirmed in risk-adjusted models (HR, 0.29 [95% CI, 0.19-0.43], P < .001), a propensity-matched cohort (HR, 0.44 [95% CI, 0.26-0.76], P = .003), and in the inverse probability-weighted analysis (HR, 0.51 [95% CI, 0.36-0.72], P < .001). Reduction in late-onset atrial fibrillation was not observed (HR, 0.85 [95% CI, 0.64-1.13], P = .26). Among registry patients with mitral valve regurgitation due to flail mitral leaflets, performance of early mitral surgery compared with initial medical management was associated with greater long-term survival and a lower risk of heart failure, with no difference in new-onset atrial fibrillation.

Impact of ageing on presentation and outcome of mitral regurgitation due to flail leaflet: a multicentre international study

Define the impact of age at diagnosis on degenerative mitral regurgitation(MR) prognosis. The Mitral regurgitation International DAtabase (MIDA) is a multicentre registry of MR due to flail leaflets including 862 patients (65 ± 12 years) diagnosed by echocardiography. The 498 older patients (≥65 years at diagnosis) were compared with the 364 younger (<65) with regard to presentation and the outcome was compared with that expected in the general population. Older vs. younger patients had MR of similar severity and ventricular overload but presented with more MR consequences and incurred higher mortality [risk ratio (rr) 95% confidence interval (95% CI) 4.7 (2.5-10.0), P < 0.001] independently of co-morbidity. Compared with expected survival [relative risk (95% confidence interval)], excess mortality, non-significant in younger patients [1.1 (0.6-2.0), P = 0.65], was prominent in older patients [1.4 (1.2-1.7), P < 0.001]. Compared with expected, excess heart failure (HF) occurred in younger [9.3 (6.5-13.3), P < 0.0001) and in older patients [6.7 (5.6-8.1), P < 0.0001]. Excess atrial fibrillation (AF) was even higher in younger [6.9 (4.5-10.6), P < 0.0001] than in older patients [3.5 (2.6-4.7), P < 0.0001; P < 0.001 for comparison between age groups]. Subsequent excess mortality [rr (95% CI)] was associated with occurrence of HF and/or AF in both age groups [13.5 (7.4-24.6), P < 0.001]. Mitral surgery was associated with reduced long-term mortality in older patients and lower rate of HF in both the age groups (all P < 0.01). Both older and younger patients incurred excess risk of complications. Older patients suffered excess mortality, AF, and HF, whereas younger incurred excess morbidity linked to subsequent long-term excess mortality. The excess risks of uncorrected degenerative MR should be considered in deliberating surgical management, which significantly reduced mortality in older patients and HF in younger patients.

Left Atrial Size Is a Potent Predictor of Mortality in Mitral Regurgitation Due to Flail Leaflets

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 &lt;55 mm, those with LA ≥55 mm had lower 8-year overall survival ( P &lt;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 &gt;0.20). Mitral surgery was associated with greater survival benefit in patients with LA ≥55 mm compared with LA &lt;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.

Prognostic and therapeutic implications of pulmonary hypertension complicating degenerative mitral regurgitation due to flail leaflet: A Multicenter Long-term International Study

To determine the frequency, predictors, and outcome implications of pulmonary hypertension (PH) diagnosed by Doppler echocardiography in a large cohort of patients with the homogenous diagnosis of degenerative mitral regurgitation (MR) due to flail leaflets. The Mitral Regurgitation International DAtabase (MIDA) is a registry including patients with MR due to flail leaflets consecutively referred at tertiary centres in Europe and the USA. Between 1987 and 2004, pulmonary artery systolic pressure (PASP) was measured at baseline by Doppler echocardiography in 437 patients (age 67 ± 11 years; 66% men). Pulmonary hypertension (PASP > 50 mmHg) was observed in 102 patients (23%). Independent predictors of PH were age and left atrial size (P < 0.0001). During a mean follow-up of 4.8 ± 2.8 years, PH was a strong independent predictor of death [adjusted HR 2.03 (1.30-3.18) P = 0.002], cardiovascular death [CVD; adjusted HR 2.21 (1.30-3.76) P = 0.003], and heart failure [adjusted HR 1.70 (1.10-2.62) P = 0.018]. Mitral valve surgery at any time during follow-up (performed in 325 patients, 75%) was beneficial [adjusted HR for death 0.22 (0.14-0.36) P < 0.001], but PH was associated with the increased risk of postoperative death and CVD (P = 0.01). Pulmonary hypertension is a frequent complication of significant MR due to flail leaflet and is associated with major outcome implications, approximately doubling the risk of death and heart failure after diagnosis. Mitral valve surgery performed during follow-up is beneficial but does not completely abolish the adverse effects of PH once it is established and is particularly beneficial in patients without PH. These data support relieving PH secondary to MR due to flail leaflet, but also careful consideration for mitral surgery before PH is established.

Primum Non Nocere: The Case for Watchful Waiting in Asymptomatic “Severe” Degenerative Mitral Regurgitation

“ The physician must … have two special objects in view with regard to disease, namely, to do good or to do no harm ” — Hippocrates 1 The optimal surgical treatment for severe mitral regurgitation resulting from degenerative disease (flail or prolapse caused by myxomatous change or fibroelastic deficiency) is mitral repair.2–5 Although the decision to intervene on a symptomatic patient is relatively straightforward, current guidelines also define other triggers for surgery in patients who are asymptomatic.6,7 In the absence of symptoms, left ventricular (LV) dysfunction, defined as an LV ejection fraction (LVEF) of 30% to 60% or an LV end-systolic diameter (LVESD) of ≥40 mm6 (>45 mm7), is a class I indication. Class IIa indications in the asymptomatic patient with preserved LV function include atrial fibrillation and pulmonary hypertension (pulmonary artery systolic pressure >50 mm Hg at rest or >60 mm Hg after exercise). It is also deemed reasonable (class IIa6 or IIb7) to regard the presence of severe mitral regurgitation as a sole and sufficient indication for surgery provided that the likelihood of repair is high (≥90%)6 and operative risk is low.7 This last recommendation has generated considerable debate because no randomized controlled trial has defined the best treatment for asymptomatic patients with severe degenerative mitral regurgitation. Proponents of prophylactic repair favor an aggressive surgical approach, whereas opponents lobby for a strategy of close medical follow-up until conventional triggers are met (watchful waiting). Here, we present our argument for watchful waiting. Response by Enriquez-Sarano and Sundt see p 813 Because by definition a strategy of prophylactic surgery in asymptomatic patients cannot improve their sense of well-being, it must be associated with better surgical and/or clinical outcomes relative to a triggered strategy. It is our position that this benefit has …

161 Survival Implication of Left Ventricular End-Systolic Diameter in Mitral Regurgitation Due to Flail Leaflets: a Long-Term Follow-Up Multicenter Study

Objectives We analyzed the association of left ventricular end-systolic diameter (LVESD) with survival after diagnosis in organic mitral regurgitation (MR) due to flail leaflets. Background LVESD is a marker of left ventricular function in patients with organic MR but its association to survival after diagnosis is unknown. Methods The Mitral regurgitation International DAtabase (MIDA) is a multicenter registry of echocardiographically-diagnosed organic MR due to flail leaflets. We enrolled 739 patients with MR due to flail leaflets (65±12 years; ejection fraction [EF] 65±10%) in whom LVESD was measured (36±7mm). Results Under conservative management, 10-year survival and survival free of cardiac death were higher with LVESD Conclusions In MR due to flail leaflets, LVESD ≥40mm is independently associated with increased mortality under medical management, but also after mitral surgery. These findings support prompt surgical rescue in patients with LVESD ≥40mm but also suggest that best preservation of survival is achieved in patients operated before LVESD reaches 40mm.

Survival Implication of Left Ventricular End-Systolic Diameter in Mitral Regurgitation Due to Flail Leaflets: A Long-Term Follow-Up Multicenter Study

This study analyzed the association of left ventricular end-systolic diameter (LVESD) with survival after diagnosis in organic mitral regurgitation (MR) due to flail leaflets. LVESD is a marker of left ventricular function in patients with organic MR but its association to survival after diagnosis is unknown. The MIDA (Mitral Regurgitation International Database) registry is a multicenter registry of echocardiographically diagnosed organic MR due to flail leaflets. We enrolled 739 patients with MR due to flail leaflets (age 65 +/- 12 years; ejection fraction: 65 +/- 10%) in whom LVESD was measured (36 +/- 7 mm). Under conservative management, 10-year survival and survival free of cardiac death were higher with LVESD <40 mm versus > or =40 mm (64 +/- 5% vs. 48 +/- 10%; p < 0.001, and 73 +/- 5% vs. 63 +/- 10%; p = 0.001). LVESD > or =40 mm independently predicted overall mortality (hazard ratio [HR]: 1.95, 95% confidence interval [CI]: 1.01 to 3.83) and cardiac mortality (HR: 3.09, 95% CI: 1.35 to 7.09) under conservative management. Mortality risk increased linearly with LVESD >40 mm (HR: 1.15, 95% CI: 1.04 to 1.27 per 1-mm increment). During the entire follow-up (including post-surgical), LVESD > or =40 mm independently predicted overall mortality (HR: 1.86, 95% CI: 1.24 to 2.80) and cardiac mortality (HR: 2.14, 95% CI: 1.29 to 3.56), due to persistence of excess mortality in patients with LVESD > or =40 mm after surgery (HR: 1.86, 95% CI: 1.11 to 3.15 for overall death, and HR: 1.81, 95% CI: 1.05 to 3.54 for cardiac death). In MR due to flail leaflets, LVESD > or =40 mm is independently associated with increased mortality under medical management but also after mitral surgery. These findings support prompt surgical rescue in patients with LVESD > or =40 mm but also suggest that best preservation of survival is achieved in patients operated before LVESD reaches 40 mm.