Diagnostic and Prognostic Accuracy of Aortic Valve Calcium Scoring in Patients With Moderate-to-Severe Aortic Stenosis.

Background: Assessing the true severity of aortic stenosis (AS) remains a challenge, particularly when echocardiography yields discordant results. Recent European and American guidelines recommend measuring aortic valve calcium (AVC) by multidetector row computed tomography (MDCT) to improve this assessment. Aim: To define, using a standardized MDCT scanning protocol, the optimal AVC load criteria for truly severe AS in patients with concordant echocardiographic findings, to establish the ability of these criteria to predict clinical outcomes, and to investigate their ability to delineate truly severe AS in patients with discordant echocardiographic AS grading. Methods and Results: Two hundred and sixty-six patients with moderate-to-severe AS and normal LVEF prospectively underwent MDCT and Doppler-echocardiography to assess AS severity. In patients with concordant AS grading, ROC analysis identified optimal cut-off values for diagnosing severe AS using different AVC load criteria. In these patients, 4-year event-free survival was better with low AVC load (60-63%) by these criteria than with high AVC load (23-26%, log rank p < 0.001). Patients with discordant AS grading had higher AVC load than those with moderate AS but lower AVC load than those with severe high-gradient AS. Between 36 and 55% of patients with severe LG-AS met AVC load criteria for severe AS. Although AVC load predicted outcome in these patients as well, its prognostic impact was less than in patients with concordant AS grading. Conclusions: Assessment of AVC load accurately identifies truly severe AS and provides powerful prognostic information. Our data further indicate that patients with discordant AS grading consist in a heterogenous group, as evidenced by their large range of AVC load. MDCT allows to differentiate between truly severe and pseudo-severe AS in this population as well, although the prognostic implications thereof are less pronounced than in patients with concordant AS grading.

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

BACKGROUND: Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery. OBJECTIVES: This study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term. METHODS: Patients 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. RESULTS: Among 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). CONCLUSIONS: AF 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.

Mid-term results of a randomized trial of tricuspid annuloplasty for less-than-severe functional tricuspid regurgitation at the time of mitral valve surgery†.

OBJECTIVES: The optimal management of functional tricuspid regurgitation (FTR) in the setting of mitral valve operations remains controversial. The current practice is both centre specific and surgeon specific with guidelines based on non-randomized data. A prospective randomized trial was performed to evaluate the worth of less-than-severe FTR repair during mitral valve procedures. METHODS: A single-centre randomized study was designed to allocate patients with less-than-severe FTR undergoing mitral valve surgery to be prophylactically treated with or without tricuspid valve annuloplasty (TVP- or TVP+). These patients were analysed using longitudinal cardiopulmonary exercise capacity, echocardiographic follow-up and cardiac magnetic resonance. The primary outcome was freedom from more than or equal to moderate tricuspid regurgitation with vena contracta ≥4 mm. Secondary outcomes were maximal oxygen uptake and right ventricular (RV) dimension and function. RESULTS: A total of 53 patients were allocated to receive concomitant TVP+, and 53 patients were treated conservatively (TVP-). At 5 years, tricuspid regurgitation was observed to be greater than mild in 10 patients in the TVP- group and no patients in the TVP+ group (P < 0.01). Maximal oxygen uptake, RV basal diameter, end-diastolic diameter and end-systolic diameter and fractional area changes were similar in both groups. Cardiac magnetic resonance confirmed no differences in RV end-diastolic volume, RV end-systolic volume and RV ejection fraction. CONCLUSIONS: This single-centre prospective randomized trial demonstrated that prophylactic tricuspid annuloplasty irrespective of annular dilatation at the time of mitral surgery reduced the recurrence of moderate or severe FTR at 5-year follow-up and reduced the pulmonary pressure. Nevertheless, the functional capacity, the RV function and the RV dimension remained similar.

Assessment of Left Ventricular Reverse Remodeling by Cardiac MRI in Patients Undergoing Repair Surgery for Severe Aortic or Mitral Regurgitation.

OBJECTIVE: To evaluate left ventricular (LV) reverse remodeling after repair surgery for mitral regurgitation (MR) or aortic regurgitation (AR), aiming at determining optimal preoperative thresholds for normalization of LV volumes and function after surgery. DESIGN: Observational prospective cohort study. SETTING: Single-center, academic, tertiary care cardiovascular center. PARTICIPANTS: Patients and volunteers. INTERVENTIONS: Cardiac magnetic resonance with measurement of indexed LV end-diastolic volume (LVEDVi) and end-systolic volume (LVESVi), mass (LVmassi), and ejection fraction (LVEF) was performed preoperatively and postoperatively. MEASUREMENTS AND MAIN RESULTS: The authors included 29 patients with AR and 59 patients with MR (46 ± 12 and 56 ± 12 years, follow-up 222 ± 57 days). Both AR and MR repair resulted in a significant reduction of LV volumes and mass (respectively, delta change in LVEDVi -55 mL/m² and -43 mL/m²; in LVESVi -26 mL/m² and -10 mL/m²; and in LVmassi -24 g/m² and -12 g/m²; p < 0.001 for all). Yet despite the absence of perioperative necrosis, 7 (24%) patients with AR had persistent LV dilatation (LVEDVi >106 mL/m²) relative to controls and 16 (27%) patients with MR developed systolic LV dysfunction (LVEF <50%) postoperatively. Binary logistic regression analysis indicated preoperative LV volumes as the most accurate parameter for predicting both incomplete LV reverse remodeling in AR and LV dysfunction in MR. Receiver operating characteristic-determined thresholds were LVEDVi >155 mL/m² for AR and >129 mL/m² for MR. CONCLUSION: Although both AR and MR repair allow significant reverse postoperative LV remodeling, persistent LV dilatation after AR correction and systolic LV dysfunction after MR repair are common and best predicted by increased preoperative LV volumes. This highlights the importance of considering LV volumes in the decision-making process.

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.

Assessment of aortic valve calcium load by multidetector computed tomography. Anatomical validation, impact of scanner settings and incremental diagnostic value.

OBJECTIVES: To validate aortic valve calcium (AVC) load measurements by multidetector row computed tomography (MDCT), to evaluate the impact of tube potential and slice thickness on AVC scores, to examine the accuracy of AVC load in distinguishing severe from nonsevere aortic stenosis (AS) and to investigate its effectiveness as an alternative diagnosis method when echocardiography remains inconclusive. METHODS: We prospectively studied 266 consecutive patients with moderate to severe AS who underwent MDCT to measure AVC load and a comprehensive echocardiographic examination to assess AS severity. AVC load was validated against valve weight in 57 patients undergoing aortic valve replacement. The dependence of AVC scores on tube potential and slice thickness was also tested, as well as the relationship between AVC load and echocardiographic criteria of AS severity. RESULTS: MDCT Agatston score correlated well with valve weight (r = 0.82, p < 0.001) and hemodynamic indices of AS severity (all p < 0.001). Ex-vivo Agatston scores decreased significantly with increasing tube potential and slice thickness (repeated measures ANOVA p < 0.001). Multivariate analysis identified mean gradient, the indexed effective orifice area, male gender and left ventricular outflow tract cross-sectional area as independent correlates of the in-vivo AVC load. CONCLUSIONS: MDCT-derived AVC load correlated well with valve weight and hemodynamic indices of AS severity. It also depends on tube potential and slice thickness, thus suggesting that these parameters should be standardized to optimize reproducibility and accuracy.

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.

Association of B-Type Natriuretic Peptide With Survival in Patients With Degenerative Mitral Regurgitation.

BACKGROUND: Studies suggesting that B-type natriuretic peptide (BNP) may predict outcomes of mitral regurgitation (MR) are plagued by small size, inconsistent etiologies, and lack of accounting for shifting normal BNP ranges with age and sex. OBJECTIVES: This study assessed the effect of BNP activation on mortality in a large, multicenter cohort of patients with degenerative MR. METHODS: In 1,331 patients with degenerative MR, BNP was prospectively measured at diagnosis and expressed as BNPratio (ratio to upper limit of normal for age, sex, and assay). Initial surgical management was performed within 3 months of diagnosis in 561 patents. RESULTS: The cohort had a mean age of 64 ± 15 years, was 66% male, and had a mean ejection fraction 64 ± 9%, mean regurgitant volume 67 ± 31 ml, and low mean Charlson comorbidity index of 1.09 ± 1.76. Median BNPratio was 1.01 (25th and 75th percentiles: 0.42 to 2.36). Overall, BNPratio was a powerful, independent predictor of mortality (hazard ratio: 1.33 [95% confidence interval: 1.15 to 1.54]; p < 0.0001), whereas absolute BNP was not (p = 0.43). In patients who were initially treated medically (n = 770; 58%), BNPratio was a powerful, independent, and incremental predictor of mortality after diagnosis (hazard ratio: 1.61 [95% confidence interval: 1.34 to 1.93]; p < 0.0001). Higher BNP activation was associated with higher mortality (p < 0.0001). All subgroups, particularly severe MR, incurred similar excess mortality with BNP activation. After initial surgical treatment (n = 561, 42%) BNP activation did not impose excess long-term mortality (p = 0.23). CONCLUSIONS: In patients with degenerative MR, BNPratio is a powerful, independent, and incremental predictor of long-term mortality under medical management. BNPratio should be incorporated into the routine clinical assessment of patients with degenerative MR.

Histological Validation of measurement of diffuse interstitial myocardial fibrosis by myocardial extravascular volume fraction from Modified Look-Locker imaging (MOLLI) T1 mapping at 3 T.

BACKGROUND: Gadolinium (Gd) Extracellular volume fraction (ECV) by Cardiovascular Magnetic Resonance (CMR) has been proposed as a non-invasive method for assessment of diffuse myocardial fibrosis. Yet only few studies used 3 T CMR to measure ECV, and the accuracy of ECV measurements at 3 T has not been established. Therefore the aims of the present study were to validate measurement of ECV by MOLLI T1 mapping by 3 T CMR against fibrosis measured by histopathology. We also evaluated the recently proposed hypothesis that native-T1 mapping without contrast injection would be sufficient to detect fibrosis. METHODS: 31 patients (age = 58 ± 17 years, 77% men) with either severe aortic stenosis (n = 12) severe aortic regurgitation (n = 9) or severe mitral regurgitation (n = 10), all free of coronary artery disease, underwent 3 T-CMR with late gadolinium enhancement (LGE) and pre- and post-contrast MOLLI T1 mapping and ECV computation, prior to valve surgery. LV biopsies were performed at the time of surgery, a median 13 [1-30] days later, and stained with picrosirius red. Pre-, and post-contrast T1 values, ECV, and amount of LGE were compared against magnitude of fibrosis by histopathology by Pearson correlation coefficients. RESULTS: The average amount of interstitial fibrosis by picrosirius red staining in biopsy samples was 6.1 ± 4.3%. ECV computed from pre-post contrast MOLLI T1 time changes was 28.9 ± 5.5%, and correlated (r = 0.78, p < 0.001) strongly with the magnitude of histological fibrosis. By opposition, neither amount of LGE (r = 0.17, p = 0.36) nor native pre-contrast myocardial T1 time (r = -0.18, p = 0.32) correlated with fibrosis by histopathology. CONCLUSIONS: ECV determined by 3 T CMR T1 MOLLI images closely correlates with histologically determined diffuse interstitial fibrosis, providing a non-invasive estimation for quantification of interstitial fibrosis in patients with valve diseases. By opposition, neither non-contrast T1 times nor the amount of LGE were indicative of the magnitude of diffuse interstitial fibrosis measured by histopathology.

Natural history of paradoxical low-gradient severe aortic stenosis.

BACKGROUND: Up to 30% of patients with severe aortic stenosis (SAS; indexed aortic valve area <0.6 cm(2)/m(2)) present with low transvalvular gradient despite a normal left ventricular ejection fraction. Presently, there is intense controversy as to the prognostic implications of such findings. Accordingly, the aim of the present work was to compare the natural history of patients with paradoxical low-gradient (PLG) or high-gradient (HG) SAS. METHODS AND RESULTS: We prospectively studied 349 patients with SAS and preserved left ventricular ejection fraction. Patients were categorized into HG-SAS (n=144) and PLG-SAS (n=205) according to mean transvalvular gradient (mean gradient >40 or ≤40 mm Hg). Primary end points were all-cause mortality and echocardiographic disease progression. To evaluate natural history, patients undergoing aortic valve replacement were censored at the time of surgery (n=92). During a median follow-up of 28 months, 148 patients died. Kaplan-Meier survival curves showed better survival in PLG-SAS than in HG-SAS, both in the overall population (48% versus 31%; P<0.01) and in the asymptomatic subgroup (59% versus 35%; P<0.02). In asymptomatic patients, Cox analysis identified age, diabetes mellitus, left atrial volume, and mean gradient as independent predictors of death. Finally, at last echocardiographic follow-up, PLG-SAS demonstrated significant increases in mean gradient (from 29±6 to 38±11 mm Hg; P<0.001). CONCLUSIONS: Our study indicates that PLG-SAS is a less malignant form of AS compared with HG-SAS, because their spontaneous outcome is better. We further demonstrated that patients with PLG-SAS are en route toward the more severe HG-SAS form, because the majority of them evolve into HG-SAS over time.