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

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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]. CONCLUSIONS: 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Factors influencing post-surgical survival in degenerative mitral regurgitation.

AIMS: Indications for surgery in patients with degenerative mitral regurgitation (DMR) are increasingly liberal in all clinical guidelines but the role of secondary outcome determinants (left atrial volume index ≥60 mL/m2, atrial fibrillation, pulmonary artery systolic pressure ≥50 mmHg and moderate to severe tricuspid regurgitation) and their impact on post-operative outcome remain disputed. Whether these secondary outcome markers are just reflective of the DMR severity or intrinsically affect survival after DMR surgery is uncertain and may have critical importance in the management of patients with DMR. To address these gaps of knowledge the present study gathered a large cohort of patients with quantified DMR, accounted for the number of secondary outcome markers and examined their independent impact on survival after surgical correction of the DMR. METHODS AND RESULTS: The Mitral Regurgitation International DAtabase-Quantitative registry includes patients with isolated DMR from centres across North America, Europe, and the Middle East. Patient enrolment extended from January 2003 to January 2020. All patients undergoing mitral valve surgery within 1 year of registry enrolment were selected. A total of 2276 patients [65 (55-73) years, 32% male] across five centres met study eligibility criteria. Over a median follow-up of 5.6 (3.6 to 8.7) years, 278 patients (12.2%) died. In a comprehensive multivariable Cox regression model adjusted for age, EuroSCORE II, symptoms, left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LV ESD) and DMR severity, the number of secondary outcome determinants was independently associated with post-operative all-cause mortality, with adjusted hazard ratios of 1.56 [95% confidence interval (CI): 1.11-2.20, P = 0.011], 1.78 (95% CI: 1.23-2.58, P = 0.002) and 2.58 (95% CI: 1.73-3.83, P < 0.0001) for patients with one, two, and three or four secondary outcome determinants, respectively. A model incorporating the number of secondary outcome determinants demonstrated a higher C-index and was significantly more concordant with post-operative mortality than models incorporating traditional Class I indications alone [the presence of symptoms (P = 0.0003), or LVEF ≤60% (P = 0.006), or LV ESD ≥40 mm (P = 0.014)], while there was no significant difference in concordance observed compared with a model that incorporated the number of Class I indications for surgery combined (P = 0.71). CONCLUSION: In this large cohort of patients treated surgically for DMR, the presence and number of secondary outcome determinants was independently associated with post-surgical survival and demonstrated better outcome discrimination than traditional Class I indications for surgery. Randomised controlled trials are needed to determine if patients with severe DMR who demonstrate a cardiac phenotype with an increasing number of secondary outcome determinants would benefit from earlier surgery.

Chronic kidney disease is a key risk factor for aortic stenosis progression.

BACKGROUND: Rapid progression of aortic stenosis (AS) has been observed in patients undergoing dialysis, but existing cross-sectional evidence is contradictory in non-dialysis-dependent chronic kidney disease (CKD). The present study sought to evaluate whether CKD is associated with the progression of AS over time in a large cohort of patients with AS. METHODS: We retrospectively studied all consecutive patients diagnosed with AS [peak aortic jet velocity (Vmax) ≥2.5 m/s] and left ventricular ejection fraction ≥50% in the echocardiography laboratories of two tertiary centers between 2000 and 2018. The estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2) was calculated from serum creatinine values. Patients were divided into five CKD stages according to the baseline eGFR. Annual rates of change in the aortic valve area (AVA) were determined by a linear mixed-effects model. RESULTS: Among the 647 patients included, 261 (40%) had CKD. After a median follow-up of 2.9 (interquartile range 1.8-4.8) years, the mean overall rate of change in AVA was -0.077 (95% confidence interval -0.082; -0.073) cm2/year. There was an inverse relationship between the progression rate and kidney function. The more severe the CKD stage, the greater the AVA narrowing (P < .001). By multivariable linear regression analysis, the eGFR was also negatively associated (P < .001) with AS progression. An eGFR strata below 45 mL/min/1.73 m2 was associated with higher odds of rapid progression of AS than normal kidney function. During the clinical follow-up, event-free survival (patients free of aortic valve replacement or death) decreased as CKD progressed. Rapid progression of AS in patients with kidney dysfunction was associated with worse outcomes. CONCLUSIONS: Patients with CKD exhibit more rapid progression of AS over time and require close monitoring. The link between kidney dysfunction and rapid progression of AS is still unknown and requires further research.

Impact of Preoperative Left Atrial Dimension on Outcome in Patients in Sinus Rhythm Undergoing Surgical Valve Repair for Severe Mitral Regurgitation due to Mitral Valve Prolapse.

BACKGROUND: Left atrial (LA) enlargement has been previously identified as a predictor of mortality in patients with medically managed mitral regurgitation (MR) due to mitral valve prolapse (MVP). No study has specifically assessed the prognostic value of LA size in patients undergoing mitral valve repair (MVRp). OBJECTIVE: We aimed to investigate the relationship between LA area and mortality in patients in sinus rhythm (SR) undergoing MVRp for MVP. METHODS: We included 305 patients in SR who underwent MVRp for MVP. Median follow-up time was 7.9 years. Patients were divided into 3 groups: LA area ≤25 cm2 (reference group), LA 26-30 cm2, and LA >30 cm2. RESULTS: Compared with patients with an LA area ≤25 cm2, those with an LA area >30 cm2 had a lower 10-year survival (98 ± 2 vs. 86 ± 4%; p = 0.037). In multivariate analysis, after adjustment for established outcome predictors including age, symptoms, EuroSCORE, and left ventricular size and function, LA enlargement >30 cm2 was associated with increased mortality (adjusted HR = 2.20, 95% CI 1.03-4.90; p = 0.042), whereas LA enlargement between 26 and 30 cm2 was not (adjusted HR = 1.37, 95% CI 0.56-3.56; p = 0.52). CONCLUSION: LA enlargement is independently predictive of long-term mortality after MVRp in patients in SR with severe MR due to MVP. Our findings suggest that MVRp should be considered before the LA area exceeds 30 cm2.

Impact of low stroke volume on mortality in patients with severe aortic stenosis and preserved left ventricular ejection fraction.

Aims: In patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF), low flow (LF) is currently defined using Doppler-echocardiography by a stroke volume index (SVi)<35 mL/m2. However, the relationship between LF and outcome remains unclear as data on normal reference values defining LF are scarce, and previous studies did not explore the risk associated with other SVi cut-points. We analysed the relationship between LF and mortality in severe AS to establish prognostic LF values associated with mortality risk. Methods and results: This study included 1450 consecutive patients with severe AS (aortic valve area <1 cm2 and/or <0.6 cm2/m2) and preserved LVEF and 1645 controls with normal echocardiograms. Patients were stratified in three groups: (i) SVi > 35 mL/m2 or SV > 70 mL; (ii) SVi 30-35 mL/m2 or SV 55-70 mL; and (iii) SVi < 30 mL/m2 or SV < 55 mL. Mortality with medical and surgical management was analysed. Five-year survival was low for SVi < 30 mL/m2 and SV < 55 mL compared to the other groups (all P-values <0.001). After adjustment for outcome predictors, including aortic valve replacement, mortality risk was considerable with SVi < 30 mL/m2 vs. >35 mL/m2 [adjusted hazard ratio (HR) 1.60 (1.17-2.18)] and SV < 55 mL vs. >70 mL [adjusted HR 1.84 (1.32-2.58)]. Similar mortality risk was observed for SVi 30-35 mL/m2 vs. >35 mL/m2 [adjusted HR 1.05 (0.78-1.41)], and for SV 55-70 mL vs. >70 mL [adjusted HR 1.22 (0.94-1.58)]. The prognostic impact of SVi < 30 mL/m2 and SV < 55 mL was consistent in subgroups, including asymptomatic patients and patients with low-gradient severe AS. Conclusion: Low flow defined as SVi < 30 mL/m2 or SV < 55 mL is an important outcome predictor in severe AS with preserved LVEF under medical and surgical management. Further studies are needed to prospectively test these values for risk stratification and decision making.

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

Aims: In degenerative mitral regurgitation (DMR), lack of mortality scores predicting death favours misperception of individual patients' risk and inappropriate decision-making. Methods and results: 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). Conclusion: 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.

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.

Impact of Preoperative Left Ventricular Remodelling Patterns on Long-Term Outcome after Aortic Valve Replacement for Severe Aortic Stenosis.

OBJECTIVES: Four patterns of left ventricular (LV) geometry have been described in aortic stenosis (AS): normal geometry, concentric remodelling (LVCR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). LVCR and CH are independently associated with an increased risk of mortality in patients with medically managed AS. No data are available on the impact of aortic valve replacement (AVR) on the negative prognostic implications of LV remodelling patterns. METHODS: This study evaluated the long-term postoperative prognostic value of preoperative LV patterns in a cohort of 779 patients (mean age 73 years) with severe AS and ejection fraction >50% undergoing AVR. RESULTS: Long-term postoperative all-cause and cardiovascular mortality in patients with LVCR (adjusted HR = 0.50 [0.17-1.45], p = 0.202, and 0.45 [0.10-2.15], p = 0.373, respectively), CH (adjusted HR = 0.98 [0.68-1.40], p = 0.915, and 1.25 [0.60-2.40], p = 0.556, respectively), or EH (adjusted HR = 1.02 [0.79-1.32], p = 0.870, and 1.18 [0.70-1.99], p = 0.537, respectively) were comparable to those of patients with normal LV geometry. CONCLUSIONS: Despite the negative prognostic impact of LVCR and CH observed in patients with medically managed AS, these LV remodelling patterns are not associated with excess mortality after AVR. Surgery should therefore be discussed in patients with LVCR or CH and severe AS to avoid the risk of increased mortality observed under conservative management.

Anatomical and functional assessment of Tryton bifurcation stent before and after final kissing balloon dilatation: Evaluations by three-dimensional coronary angiography, optical coherence tomography imaging and fractional flow reserve.

OBJECTIVES: To assess the anatomical and functional impact of final kissing balloon inflation (FKBI) after implantation of a dedicated bifurcation stent system. BACKGROUND: Current evidence suggests clinical benefit of FKBI in patients undergoing bifurcation dilatation using the Tryton side branch stent (Tryton-SBS). We hypothesized that FKBI improves anatomical reconstruction and functional results of bifurcation treated by Tryton-SBS. METHODS: An unselected group of patients with complex bifurcation coronary lesions undergoing percutaneous coronary intervention (PCI) with Tryton-SBS underwent paired anatomical assessment with two- and three-dimensional quantitative coronary analysis (2D- and 3D-QCA), and optical coherence tomography (OCT), including 3D reconstruction before and after FKBI. Functional assessment by fractional flow reserve (FFR) was performed in the main branch (MB) and side branch (SB) before and after FKBI. RESULTS: Paired pre- and post-FKBI data were obtained in 10 patients. By OCT imaging, FKBI increased both the SB ostial area (4.93 ± 2.81 vs. 7.43 ± 2.87 mm2 , P < 0.001) and the SB maximum diameter (3.12 ± 0.98 vs. 3.82 ± 1.10 mm, P = 0.003). These findings were associated with a significant increase in FFR in the SB (0.90 ± 0.05 vs. 0.94 ± 0.03; P = 0.011), with no significant change in the MB (0.91 ± 0.05 vs. 0.92 ± 0.04; P = 0.470). CONCLUSIONS: In patients with complex bifurcation stenosis undergoing PCI with a dedicated bifurcation system, FKBI is associated with improved anatomical and functional results at the SB level, without compromising the result at the MB. © 2016 Wiley Periodicals, Inc.

Bioabsorbable polymer-coated sirolimus-eluting stent implantation preserves coronary vasomotion: A DESSOLVE II trial sub-study.

OBJECTIVES: We studied coronary vasomotion in patients treated with the Mistent(®) absorbable polymer sirolimus-eluting stent (APSES) and in patients implanted with the Endeavor(®) zotarolimus-eluting stent (ZES). BACKGROUND: First generation (1st-gen) drug-eluting stents (DES) induce persistent vasomotor dysfunction in the treated coronary artery. It is unknown whether and to what extent the implantation of an absorbable polymer DES impairs coronary vasomotion. METHODS: This sub-study of the DESSOLVE II trial included 19 APSES Mistent(®) and 10 ZES Endeavor(®) patients. Incremental atrial pacing and quantitative coronary angiography were used to assess vasomotion proximal and distal to the stent and in a reference segment at 9 months after implantation. Percent changes in vessel diameter with pacing versus baseline were calculated and compared. Vasomotor response of the APSES group was also compared with changes observed in a historical group of 17 patients implanted with a 1st-gen sirolimus-eluting stent (SES). RESULTS: Normal vasomotion (vasodilatation) was preserved and of comparable magnitude in the APSES and in the ZES group both proximally (P = 0.34) and distally (P = 0.38) to the stent. This finding was not observed in the 1st-gen SES group showing marked pacing-induced vasoconstriction at both stent edges (P < 0.05 vs. APSES). The results were practically unchanged after excluding patients with absolute changes in vessel diameter <3% between baseline and maximal pacing. CONCLUSIONS: The implantation of an absorbable polymer sirolimus-eluting stent is associated with preserved coronary vasomotion, comparable to that observed after implantation of the Endeavor(®) ZES, and distinct from 1st-gen SES which induce coronary vasomotor dysfunction.

Frequency of drug-induced valvular heart disease in patients previously exposd to benfluorex: a multicentre prospective study.

AIMS: The epidemiologic link between benfluorex use and an increased global frequency of left heart valve regurgitation has been well documented. However, no data linking previous drug exposure to the frequency of diagnosis of drug-induced valvular heart disease (DI-VHD) are available. The present study was conducted to address this issue. METHODS AND RESULTS: This echocardiography reader-blinded, controlled study conducted in 10 centres between February 2010 and February 2012 prospectively included 835 subjects previously exposed to benfluorex referred by primary care physicians for echocardiography. Based on blinded off-line analysis, echocardiography findings were classified as: (i) DI-VHD⁺ for patients with an echocardiographic diagnosis of DI-VHD, (ii) inconclusive, and (iii) DI-VHD⁻ for patients without signs of DI-VHD. Fifty-seven (6.8%) patients exposed to benfluorex were classified as DI-VHD⁺, 733 (87.8%) patients were classified as DI-VHD⁻, and 45 (5.4%) were classified as inconclusive. Mitral and aortic DI-VHD were reported in 43 patients (5.1%) and 30 (3.6%) patients, respectively. Longer duration of exposure, female gender, smoking, and lower BMI were independently associated with a diagnosis of DI-VHD. Good inter-observer reproducibility was observed for the echocardiography classification (Kappa = 0.83, P < 0.00001). CONCLUSIONS: About 7% of patients without a history of heart valve disease previously exposed to benfluorex present echocardiography features of DI-VHD. Further studies are needed to study the natural history of DI-VHD and to identify risk factors for the development of drug-induced valve lesions.

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

AIMS: Define the impact of age at diagnosis on degenerative mitral regurgitation (MR) prognosis. METHODS AND RESULTS: 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). CONCLUSIONS: 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.

Quantifying the Survival Loss Linked to Late Therapeutic Indication in High-Gradient Severe Aortic Stenosis.

Background: International guidelines recommend aortic valve replacement (AVR) as Class I triggers in high-gradient severe aortic stenosis (HGSAS) patients with symptoms and/or left ventricular ejection fraction (LVEF) <50%. The association between waiting for these triggers and postoperative survival penalty is poorly studied. Objectives: The purpose of this study was to examine the impact of guideline-based Class I triggers on long-term postoperative survival in HGSAS patients. Methods: 2,030 patients operated for HGSAS were included and classified as follows: no Class I triggers (no symptoms and LVEF >50%, n = 853), symptoms with LVEF >50% (n = 965), or LVEF <50% regardless of symptoms (n = 212). Survival was compared after matching (inverse probability weighting) for clinical differences. Restricted mean survival time was analyzed to quantify lifetime loss. Results: Ten-year survival was better without any Class I trigger than with symptoms or LVEF <50% (67.1% ± 3% vs 56.4% ± 3% vs 53.1% ± 7%, respectively, P < 0.001). Adjusted death risks increased significantly in operated patients with symptoms (HR: 1.45 [95% CI: 1.15-1.82]) or LVEF <50% (HR: 1.47 [95% CI: 1.05-2.06]) than in those without Class I triggers. Performing AVR with LVEF >60% produced similar outcomes to that of the general population, whereas operated patients with LVEF <60% was associated with a 10-year postoperative survival penalty. Furthermore, according to restricted mean survival time analyses, operating on symptomatic patients or with LVEF <60% led to 8.3- and 11.4-month survival losses, respectively, after 10 years, compared with operated asymptomatic patients with a LVEF >60%. Conclusions: Guideline-based Class I triggers for AVR in HGSAS have profound consequences on long-term postoperative survival, suggesting that HGSAS patients should undergo AVR before trigger onset. Operating on patients with LVEF <60% is already associated with a 10-year postoperative survival penalty questioning the need for an EF threshold recommending AVR in HGSAS patients.

Reappraisal of the Concept and Implications of Pulmonary Hypertension in Degenerative Mitral Regurgitation.

BACKGROUND: European and U.S. clinical guidelines diverge regarding pulmonary hypertension (PHTN) in degenerative mitral regurgitation (DMR). Gaps in knowledge underpinning these divergences affect risk assessment and management recommendations attached to systolic pulmonary pressure (SPAP) in DMR. OBJECTIVES: This study sought to define PHTN links to DMR severity, prognostic thresholds, and independent outcome impact in a large quantitative DMR registry. METHODS: This study gathered a large multicentric registry of consecutive patients with isolated moderate-to-severe DMR, with DMR and SPAP quantified prospectively at diagnosis. RESULTS: In 3,712 patients (67 ± 15 years, 36% women) with ≥ moderate-to-severe DMR, effective regurgitant orifice (ERO) was 0.42 ± 0.19 cm2, regurgitant volume 66 ± 327 mL/beat and SPAP 41 ± 16 mm Hg. Spline-curve analysis showed excess mortality under medical management emerging around SPAP 35 mm Hg and doubling around SPAP 50 mm Hg. Accordingly, severe pulmonary hypertension (sPHTN) (SPAP ≥50 mm Hg) was detected in 916 patients, moderate pulmonary hypertension (mPHTN) (SPAP 35-49 mm Hg) in 1,128, and no-PHTN (SPAP <35 mm Hg) in 1,668. Whereas SPAP was strongly associated with DMR-ERO, nevertheless excess mortality with sPHTN (adjusted HR: 1.65; 95% CI: 1.24-2.20) and mPHTN (adjusted HR: 1.44; 95% CI: 1.11-1.85; both P ≤ 0.005) was observed independently of ERO and all baseline characteristics and in all patient subsets. Nested models demonstrated incremental prognostic value of mPHTN and sPHTN (all P < 0.0001). Despite higher operative risk with mPHTN and sPHTN, DMR surgical correction was followed by higher survival in all PHTN ranges with strong survival benefit of early surgery (<3 months). Postoperatively, excess mortality was abolished (P ≥ 0.30) in mPHTN, but only abated in sPHTN. CONCLUSIONS: This large international registry, with prospectively quantified DMR and SPAP, demonstrates a Doppler-defined PHTN impact on mortality, independent of DMR severity. Crucially, it defines objectively the new and frequent mPHTN range, independently linked to excess mortality under medical management, which is abolished by DMR correction. Thus, at DMR diagnosis, Doppler-SPAP measurement defining these new PHTN ranges, is crucial to guiding DMR management.

Increased risk of left heart valve regurgitation associated with benfluorex use in patients with diabetes mellitus: a multicenter study.

BACKGROUND: Benfluorex was withdrawn from European markets in June 2010 after reports of an association with heart valve lesions. The link between benfluorex and valve regurgitations was based on small observational studies and retrospective estimations. We therefore designed an echocardiography-based multicenter study to compare the frequency of left heart valve regurgitations in diabetic patients exposed to benfluorex for at least 3 months and in diabetic control subjects never exposed to the drug. METHODS AND RESULTS: This reader-blinded, controlled study conducted in 10 centers in France between February 2010 and September 2011 prospectively included 376 diabetic subjects previously exposed to benfluorex who were referred by primary care physicians for echocardiography and 376 diabetic control subjects. Through the use of propensity scores, 293 patients and 293 control subjects were matched for age, sex, body mass index, smoking, dyslipidemia, hypertension, and coronary artery disease. The main outcome measure was the frequency of mild or greater left heart valve regurgitations. In the matched sample, the frequency and relative risk (odds ratio) of mild or greater left heart valve regurgitations were significantly increased in benfluorex patients compared with control subjects: 31.0% versus 12.9% (odds ratio, 3.55; 95% confidence interval, 2.03-6.21) for aortic and/or mitral regurgitation, 19.8% versus 4.7% (odds ratio, 5.29; 95% confidence interval, 2.46-11.4) for aortic regurgitation, and 19.4% versus 9.6% (odds ratio, 2.38; 95% confidence interval, 1.27-4.45) for mitral regurgitation. CONCLUSIONS: Our results indicate that the use of benfluorex is associated with a significant increase in the frequency of left heart valve regurgitations in diabetic patients. The natural history of benfluorex-induced valve abnormalities needs further research.

Outcomes of pseudo-severe aortic stenosis under conservative treatment.

AIMS: In the setting of low-flow/low-gradient aortic stenosis (LF/LGAS), outcomes of pseudo-severe aortic stenosis (AS) remain poorly described. This study was aimed to assess the outcome of patients with pseudo-severe AS under conservative treatment. METHODS AND RESULTS: Among 305 patients from the European Registry of LF/LGAS, the outcomes of the 107 patients followed under conservative treatment were analysed. Based on the results of dobutamine echocardiography, patients were divided into group IA [left ventricular (LV) contractile reserve present with true-severe AS, n = 43], group IB [pseudo-severe AS (n = 29) defined as LV contractile reserve with a final aortic valve area ≥1.2 cm(2) and a mean transaortic pressure gradient <40 mmHg at peak dobutamine infusion], or group II (exhausted LV contractile reserve, n = 35). The rate of death within 5 years was significantly lower in the group IB (43 ± 11%, n = 10), when compared with the group IA (91 ± 6%, n = 33; P = 0.001) and the group II (100%, n = 23; P < 0.001). The Cox proportional hazard model analysis demonstrated that the hazard ratio for death in the group IB remained significantly lower than in the other groups, even after adjustment for currently established risk factors. Furthermore, the 5-year survival of pseudo-severe AS patients was comparable with that of propensity-matched patients with systolic heart failure and no evidence of valve disease. CONCLUSION: In patients with pseudo-severe AS, the 5-year survival under conservative treatment is better than in true-severe AS and comparable with that of propensity-matched patients with LV systolic dysfunction and no evidence of valve disease. Further studies are needed to define optimal therapeutic management in these patients.

Association between early surgical intervention vs watchful waiting and outcomes for mitral regurgitation due to flail mitral valve leaflets.

IMPORTANCE: 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. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: Association between treatment strategy and survival, heart failure, and new-onset atrial fibrillation. RESULTS: 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). CONCLUSION AND RELEVANCE: 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.

Atrial fibrillation in severe aortic stenosis: Prognostic value and results of aortic valve replacement.

OBJECTIVES: Although atrial fibrillation (AF) is common, its impact on long-term mortality has not been reliably determined in patients with aortic stenosis (AS). We aimed to assess whether AF is associated with survival in patients with severe AS and to determine the impact of AF on the results of aortic valve replacement (AVR). METHODS: The study included 1838 consecutive patients with severe AS (77 ± 11 years, male 47%). Upon AS diagnosis, patients were screened for AF using a 12-lead electrocardiogram. The treatment strategy (conservative management or AVR) was selected by the heart team in accordance with current guidelines. The effect of AVR on survival was analyzed as a time-dependent covariate using the entire follow-up period. RESULTS: AF, diagnosed in 593 (32%) patients was associated with poor survival at 5 years (55 ± 2% vs 74 ± 1% for patients in sinus rhythm, P < .001), even after adjustment for established outcome predictors (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.33-1.84; P < .001). In patients with AF, AVR was associated with lower mortality (HR, 0.16; 95% CI, 0.12-0.22; P < .001) even in those with no or minimal symptoms (HR, 0.12; 95% CI, 0.08-0.20; P < .001). However, among patients who underwent AVR, those in AF had an excess mortality (HR, 1.59; 95% CI, 1.22-2.08; P < .001). CONCLUSIONS: In severe AS, AF is a strong predictor of mortality even in asymptomatic or minimally symptomatic patients. After AVR, AF remains associated with poorer survival than sinus rhythm. In patients in AF, AVR is associated with lower mortality compared with conservative treatment. Further studies are needed to confirm the benefits of AVR in asymptomatic patients in AF with severe AS.