The Pixel Variation Score: An Echocardiographic Index to Assess Temporal Variation of Mitral Regurgitant Flow.

BACKGROUND: In mitral regurgitation (MR), temporal variation of MR flow has been considered an important reason for inaccurate MR grading. Current echocardiographic methods for assessing temporal MR flow variation are complex, and their clinical relevance has not been investigated. In this study, we investigated whether assessing MR flow variation using a dimensionless index with echocardiography is feasible, clinically meaningful, and related to patient outcomes. METHODS: Consecutive patients with mitral valve prolapse (MVP, n = 244) and functional MR (FMR, n = 396) underwent comprehensive echocardiography. Mitral regurgitation severity was assessed using an integrated approach advocated by current guidelines. The MR continuous-wave Doppler envelope was divided into 3 segments of equal duration. Each segment's pixel intensity was assessed to calculate the pixel variation score (PVS). RESULTS: The PVS was lower in FMR patients than in MVP patients. Lower PVS was associated with worse MR, larger left atrial and left ventricular dimensions, lower ejection fraction, and higher pulmonary artery pressures. In MVP, PVS was significantly associated with postoperative left ventricular reverse remodeling and was able to reclassify most patients in whom single-frame measures overestimated MR severity. Finally, PVS had incremental prognostic value on top of clinical and echocardiographic predictors of outcome. CONCLUSIONS: Temporal variation in MR flow can reliably be assessed with echocardiography through analysis of the continuous-wave Doppler signal. A high PVS value may alert the echocardiographer to defer from single-frame MR grading and also suggests that the MR is probably not severe.

Mitral Annular Disjunction: Associated Pathologies and Clinical Consequences.

PURPOSE OF REVIEW: To provide an overview of mitral annular disjunction (MAD) and to discuss important challenges in diagnosis and management of MAD. RECENT FINDINGS: MAD has regained interest in the context of sudden cardiac death (SCD) in patients with mitral valve prolapse (MVP), coined as the "arrhythmic" MVP syndrome. In addition, MAD in isolation was recently suggested to be associated with severe arrhythmia and SCD. There is a lack of consensus on the definition of MAD and the imaging modality to be used for diagnosing MAD, and the therapeutic implications of MAD remain uncertain. Furthermore, the exact mechanism underlying the association of MAD with SCD remains largely unexplored.

Color Doppler Splay in Mitral Regurgitation: Hemodynamic Correlates and Outcomes in a Clinical Cohort.

BACKGROUND: Recently, an artifactual horizontal extension of the color Doppler signal was described in patients with mitral regurgitation (MR), called color Doppler splay (CDS). This side-lobe artifact was shown to be associated with concealed and significant MR. In the present study, the authors assessed the prognostic significance of CDS and its hemodynamic correlates. METHODS: Consecutive patients with primary and secondary MR underwent comprehensive transthoracic echocardiography. Machine settings were fixed for all patients. MR severity was assessed using an integrated approach, as advocated in current international guidelines. The presence of CDS and CDS width and duration were assessed. The outcome measures included the incidence of major adverse cardiac events (a composite of cardiovascular mortality, hospitalization for decompensated heart failure, mitral valve surgery, or percutaneous mitral intervention). RESULTS: One hundred twenty-seven of 469 patients (27%) with MR demonstrated CDS. The presence of CDS was associated with worse MR, and CDS width correlated with effective regurgitant orifice area, regurgitant volume, and vena contracta width. Mitral annular or leaflet calcification was inversely associated with the presence of CDS. Patients with CDS experienced worse event-free survival. For CDS width, a cutoff of >29 mm was identified as optimal regarding outcome prediction in our cohort and termed "severe CDS." In multivariate Cox regression, the presence of severe CDS was associated with adverse outcome, independent of MR etiology or severity and other clinical and echocardiographic predictors of outcome, and provided incremental prognostic value on top of these parameters. CONCLUSIONS: In patients with MR, the presence of CDS is associated with more severe MR and worse outcomes. Severe CDS provides incremental prognostic value on top of traditional MR metrics and should alert the echocardiographer that MR severity may be underestimated.

Prognostic value of myocardial work and global longitudinal strain in patients with heart failure and functional mitral regurgitation.

In patients with heart failure and functional mitral regurgitation (FMR), the assessment of left ventricular (LV) function is important for risk stratification and decision making. As LV ejection fraction (LVEF) might not be an optimal metric for LV systolic performance in this population, alternatives such as global longitudinal strain (GLS) and global myocardial work index (GWI) have been proposed. In the present study, we investigated the prognostic value of GLS and GWI and compared these measures to other LV systolic performance parameters. A prospective and consecutive cohort of 181 patients (median age 72 years, 76% male) with LVEF < 50% and FMR underwent comprehensive echocardiographic examination including speckle tracking echocardiography and grading of FMR severity. During a median follow-up of 42 months, 72 cardiovascular (CV) events occurred. In univariate analysis, LVEF, GLS, GWI, mitral S', LV outflow tract time velocity integral, forward LVEF and LV ejection time were associated with CV events. After multivariate adjustment only GLS (hazard ratio (HR) = 0.884, p = 0.015) and GWI (HR = 0.927, p = 0.034) remained independently associated with CV events. There was no difference in the incremental prognostic value of GWI compared to GLS (delta -2 log likelihood = 0.8; p = 0.37). In this cohort of heart failure patients with FMR, GLS and GWI were independently associated with cardiovascular events, whereas other systolic performance parameters were not. However, GWI did not outperform GLS, and further research is required to determine the value of these strain-based measures in clinical practice.

Study of the time-relationship of the mechano-electrical interaction in an animal model of tetralogy of Fallot: implications for the risk assessment of ventricular arrhythmias.

OBJECTIVES: The long-term outcome of tetralogy of Fallot (TOF) is determined by progressive right ventricular (RV) dysfunction through pulmonary regurgitation (PR) and the risk of malignant arrhythmia. Although mechano-electrical coupling in TOF is well-known, its time effect on the inducibility of arrhythmia remains ill-defined. The goal of this study was to investigate the mechano-electrical properties at different times in animals with chronic PR. METHODS: PR was induced by a transannular patch with limited RV scarring in infant pigs. Haemodynamic assessment included biventricular pressure-volume loops after 3 (n = 8) and 6 months (n = 7) compared to controls (n = 5). The electrophysiological study included endocardial monophasic action potential registration, intraventricular conduction velocity and induction of ventricular arrhythmia by burst pacing. RESULTS: Progressive RV dilation was achieved at 6 months (RV end-diastolic volume 143 ± 13 ml/m2-RV end-systolic volume 96 ± 7 ml/m2; P < 0.001), in association with depressed RV contractility (preload recruitable stroke work-slope: 19 ± 1 and 11 ± 3 Mw.ml-1.s-1 for control and 6 m; P < 0.001) and left ventricular contractility (preload recruitable stroke work-slope: 60 ± 13 and 40 ± 11 Mw.ml-1.s-1 for control and 6 m; P = 0.005). Concomitant to QRS prolongation, monophasic action potential90-duration and dispersion at the RV and left ventricle were increased at 6 months. Intraventricular conduction was delayed only in the RV at 6 months (1.8 ± 0.2 and 2.4 ± 0.6 m/s for group 6M and the control group; P = 0.035). Sustained ventricular arrhythmias were not inducible. CONCLUSIONS: In animals yielding the sequelae of a contemporary operation for TOF, mechano-electrical alterations are progressive and affect predominantly the RV after midterm exposure of PR. Because ventricular arrhythmias were not inducible despite significant RV dilation, the data suggest that the haemodynamic RV deterioration effectively precedes the risk of inducing sustained arrhythmia after TOF repair and opens a window for renewed stratification of contemporary risk factors of ventricular arrhythmias in patients operated on with currently used pulmonary valve- and RV-related techniques.

Ten-year results of aortic valve replacement with first-generation Mitroflow bioprosthesis: is early degeneration a structural or a technical issue?

OBJECTIVES: Concerns have been raised about the durability of the first-generation Mitroflow aortic bioprosthesis (model 12 A-LX) due to the lack of anticalcification treatment. This study reflects a 10-year experience with this prosthesis for aortic valve replacement. METHODS: From June 2003 to May 2012, the Mitroflow prosthesis was used for aortic valve replacement in 510 patients, of whom only 467 with complete clinical follow-up were included for analysis. Study end-points were survival and incidence of structural valve degeneration (SVD). Analysis of SVD was based on cumulative incidence function and competing-risk Cox regression. RESULTS: The mean patient age was 76.4 ± 6.1 years. Valve sizes from 23 to 25 were used in 70.4%, whereas sizes from 19 to 21 were used in only 19.2%, thereby avoiding patient-prosthesis mismatch in 89.1%. Within a median follow-up time of 6.6 years (interquartile range 4.4), a cumulative 2375 patient-years, the survival rate was 86.2%, 67.3% and 33.3% at 1, 5 and 10 years, respectively. The cumulative incidence of SVD, with death as a competing risk, was 0%, 0.7% and 6.2% at 1, 5 and 10 years, respectively. Only age <75 years tended to affect the late hazard of SVD (hazard ratio 0.50, 95% confidence interval 0.23-1.08, P = 0.08), regardless of valve-specific issues. CONCLUSIONS: The data do not support the concerns about early accelerated structural degeneration of the first-generation Mitroflow bioprosthesis used for aortic valve replacement in patients older than 75 years. We postulate that limiting the number of small prostheses using a proper implantation technique has enhanced the reduction in risk of significant patient-prosthesis mismatch as the main determinant of early SVD.

A multilevel framework to reconstruct anatomical 3D models of the hepatic vasculature in rat livers.

The intricate (micro)vascular architecture of the liver has not yet been fully unravelled. Although current models are often idealized simplifications of the complex anatomical reality, correct morphological information is instrumental for scientific and clinical purposes. Previously, both vascular corrosion casting (VCC) and immunohistochemistry (IHC) have been separately used to study the hepatic vasculature. Nevertheless, these techniques still face a number of challenges such as dual casting in VCC and limited imaging depths for IHC. We have optimized both techniques and combined their complementary strengths to develop a framework for multilevel reconstruction of the hepatic circulation in the rat. The VCC and micro-CT scanning protocol was improved by enabling dual casting, optimizing the contrast agent concentration, and adjusting the viscosity of the resin (PU4ii). IHC was improved with an optimized clearing technique (CUBIC) that extended the imaging depth for confocal microscopy more than five-fold. Using in-house developed software (DeLiver), the vascular network - in both VCC and IHC datasets - was automatically segmented and/or morphologically analysed. Our methodological framework allows 3D reconstruction and quantification of the hepatic circulation, ranging from the major blood vessels down to the intertwined and interconnected sinusoids. We believe that the presented framework will have value beyond studies of the liver, and will facilitate a better understanding of various parenchymal organs in general, in physiological and pathological circumstances.