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.

Prognostic Implications of Discordant Low-Gradient Severe Aortic Stenosis: Comprehensive Analysis of a Large Multicenter Registry.

Background: Up to 30% of patients with severe aortic stenosis (SAS) (indexed aortic valve area [AVAi] <0.6 cm2/m2) exhibit low-transvalvular gradient despite normal ejection fraction. There is intense debate regarding the prognostic significance of this entity. Objectives: The purpose of this study was to compare the outcome of patients with discordant low-gradient SAS (DLG-SAS) vs moderate aortic stenosis (MAS) and high-gradient SAS (HG-SAS). Methods: We used the BEL-F-ASt (Belgium-France-Aortic Stenosis) registry including consecutive patients with AS. Survival was compared overall and after matching (inverse probability weighting and propensity-score matching) for clinical and imaging variables. The analysis was first performed in the overall population (n = 2,582) and then in the population of unoperated patients (n = 1,812). Results: After-inverse probability weighting-matching, the 3 groups were balanced. Five-year survival was better in MAS than in DLG-SAS and HG-SAS-patients (58.9% vs 47% vs 41.2%, P < 0.001). Similar results were obtained in unoperated patients (54.1% vs 37.9% vs 28.1%, P < 0.001). To explore the impact of MG (≤40 vs >40 mmHg) and AVAi (<0.6 vs ≥0.6 cm2/m2) on outcomes, survival of propensity score-matched cohorts of HG-vs DLG-SAS and MAS vs DLG-SAS were compared. After matching for MG, survival was better in MAS than in DLG-SAS (52% vs 40%, P < 0.001). After matching for AVAi, survival was better in DLG-SAS than in HG-SAS patients (45% vs 33%, P < 0.001). Conclusions: Survival of DLG-SAS is better than that of HG-SAS and worse than that of MAS patients. At comparable MG, the lower the AVAi, the worse the prognosis, whereas at comparable AVAi, the higher the MG, the worse the prognosis. These data argue that DLG-SAS is an intermediate form in the disease continuum.

Multivendor comparison of global and regional 2D cardiovascular magnetic resonance feature tracking strains vs tissue tagging at 3T.

BACKGROUND: Cardiovascular magnetic resonance (CMR) 2D feature tracking (FT) left ventricular (LV) myocardial strain has seen widespread use to characterize myocardial deformation. Yet, validation of CMR FT measurements remains scarce, particularly for regional strain. Therefore, we aimed to perform intervendor comparison of 3 different FT software against tagging. METHODS: In 61 subjects (18 healthy subjects, 18 patients with chronic myocardial infarction, 15 with dilated cardiomyopathy, and 10 with LV hypertrophy due to hypertrophic cardiomyopathy or aortic stenosis) were prospectively compared global (G) and regional transmural peak-systolic Lagrangian longitudinal (LS), circumferential (CS) and radial strains (RS) by 3 FT software (cvi42, Segment, and Tomtec) among each other and with tagging at 3T. We also evaluated the ability of regional LS, CS, and RS by different FT software vs tagging to identify late gadolinium enhancement (LGE) in the 18 infarct patients. RESULTS: GLS and GCS by all 3 software had an excellent agreement among each other (ICC = 0.94-0.98 for GLS and ICC = 0.96-0.98 for GCS respectively) and against tagging (ICC = 0.92-0.94 for GLS and ICC = 0.88-0.91 for GCS respectively), while GRS showed inconsistent agreement between vendors (ICC 0.10-0.81). For regional LS, the agreement was good (ICC = 0.68) between 2 vendors but less vs the 3rd (ICC 0.50-0.59) and moderate to poor (ICC 0.44-0.47) between all three FT software and tagging. Also, for regional CS agreement between 2 software was higher (ICC = 0.80) than against the 3rd (ICC = 0.58-0.60), and both better agreed with tagging (ICC = 0.70-0.72) than the 3rd (ICC = 0.57). Regional RS had more variation in the agreement between methods ranging from good (ICC = 0.75) to poor (ICC = 0.05). Finally, the accuracy of scar detection by regional strains differed among the 3 FT software. While the accuracy of regional LS was similar, CS by one software was less accurate (AUC 0.68) than tagging (AUC 0.80, p < 0.006) and RS less accurate (AUC 0.578) than the other two (AUC 0.76 and 0.73, p < 0.02) to discriminate segments with LGE. CONCLUSIONS: We confirm good agreement of CMR FT and little intervendor difference for GLS and GCS evaluation, with variable agreement for GRS. For regional strain evaluation, intervendor difference was larger, especially for RS, and the diagnostic performance varied more substantially among different vendors for regional strain analysis.

Inter-joint coordination and the flexion-relaxation phenomenon among adults with low back pain during bending.

BACKGROUND: Altered inter-joint coordination and reduced flexion-relaxation at end-range trunk flexion are common in people with low back pain. Inconsistencies in these behaviors, however, make assessment and treatment challenging for this population. RESEARCH QUESTION: The study objective was to investigate patterns of regional lumbo-pelvic coordination and flexion-relaxation in adults with and without low back pain, during a bending task. METHODS: Adults with low back pain (n = 16) and a healthy group (n = 21) performed three trials of a bending task. Motion capture and surface electromyography systems measured joint kinematics (hip, lower and upper lumbar spine) and muscle activity (erector spinae longissimus, iliocostalis, and multifidus). Continuous relative phase analysis determined inter-joint coordination of the hip/lower lumbar and lower lumbar/upper lumbar joint pairs, during flexion and extension periods. Flexion-relaxation ratios using normalized surface electromyography data determined the extent of flexion-relaxation for each muscle, during each period. For inter-joint coordination, two-way repeated measure mixed ANOVAs calculated the effects of group (healthy/low back pain), period, and their interactions. Separate hierarchical linear models were constructed and tested relationships between flexion-relaxation ratios and our independent variables, group and muscle, while controlling for patient characteristics. RESULTS: The low back pain group had more out-of-phase coordination of the hip/lower lumbar joint pair compared to the healthy group (mean difference = 24.7°; 95 % confidence interval = 3.93-45.4), independent of movement period. No significant between group differences in lower lumbar/upper lumbar coordination were observed. The low back pain group demonstrated reduced flexion-relaxation of all muscles during full flexion (21.7 % reduction on average), with multifidus showing the least relaxation. SIGNIFICANCE: Regional differences in the lumbar spine and the possibility of subgroups with distinct movement pattern should be considered when analyzing coordination in people with low back pain. Multifidus showed the largest changes in flexion-relaxation and should be included when measuring this construct.

Prognostic Value of Pulmonary Transit Time by Cardiac Magnetic Resonance on Mortality and Heart Failure Hospitalization in Patients With Advanced Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Pulmonary transit time (PTT) from first-pass perfusion imaging is a novel parameter to evaluate hemodynamic congestion by cardiac magnetic resonance (cMR). We sought to evaluate the additional prognostic value of PTT in heart failure with reduced ejection fraction over other well-validated predictors of risk including the Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. METHODS: We prospectively followed 410 patients with chronic heart failure with reduced ejection fraction (61±13 years, left ventricular (LV) ejection fraction 24±7%) who underwent a clinical cMR to assess the prognostic value of PTT for a primary endpoint of overall mortality and secondary composite endpoint of cardiovascular death and heart failure hospitalization. Normal reference values of PTT were evaluated in a population of 40 asymptomatic volunteers free of cardiovascular disease. Results PTT was significantly increased in patients with heart failure with reduced ejection fraction as compared to controls (9±6 beats and 7±2 beats, respectively, P<0.001), and correlated not only with New York Heart Association class, cMR-LV and cMR-right ventricular (RV) volumes, cMR-RV and cMR-LV ejection fraction, and feature tracking global longitudinal strain, but also with cardiac output. Over 6-year median follow-up, 182 patients died and 200 reached the secondary endpoint. By multivariate Cox analysis, PTT was an independent and significant predictor of both endpoints after adjustment for Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. Importantly in multivariable analysis, PTT in beats had significantly higher additional prognostic value to predict not only overall mortality (χ2 to improve, 12.3; hazard ratio, 1.35 [95% CI, 1.16-1.58]; P<0.001) but also the secondary composite endpoints (χ2 to improve=20.1; hazard ratio, 1.23 [95% CI, 1.21-1.60]; P<0.001) than cMR-LV ejection fraction, cMR-RV ejection fraction, LV-feature tracking global longitudinal strain, or RV-feature tracking global longitudinal strain. Importantly, PTT was independent and complementary to both pulmonary artery pressure and reduced RV ejection fraction<42% to predict overall mortality and secondary combined endpoints. CONCLUSIONS: Despite limitations in temporal resolution, PTT derived from first-pass perfusion imaging provides higher and independent prognostic information in heart failure with reduced ejection fraction than clinical and other cMR parameters, including LV and RV ejection fraction or feature tracking global longitudinal strain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03969394.

Additional Prognostic Value of 2D Right Ventricular Speckle-Tracking Strain for Prediction of Survival in Heart Failure and Reduced Ejection Fraction: A Comparative Study With Cardiac Magnetic Resonance.

OBJECTIVES: This study sought to compare the prognostic value of 2-dimensional (2D) right ventricular (RV) speckle tracking (STE) against cardiac magnetic resonance (CMR) RV ejection fraction (EF) and feature tracking (FT) and conventional echocardiographic parameters on overall and cardiovascular (CV) survival in patients with heart failure with reduced EF (HFrEF). BACKGROUND: Prior works showed that RV systolic function predicts prognosis in HFrEF. 2D RVSTE had recently been proposed as new echocardiographic method to evaluate RV dysfunction. METHODS: A total of 266 patients with HFrEF (mean LVEF 23 ± 7%, 60 ± 14 years of age; 29% women) underwent RV function assessment using CMR and 2D echocardiography and were followed for a primary endpoint of overall death and secondary endpoint of CV death. RESULTS: Average CMR-RVEF was 42 ± 15%, average STE RV global longitudinal strain (STE-RVGLS) was -18.0 ± 4.9%, and average CMR-FT-RVGLS was -11.8 ± 4.3%. After a median follow-up of 4.7 years, 102 patients died, 84 of a CV cause. RVEF, FT-RVGLS, tricuspid annulus plane systolic excursion (TAPSE), fractional area change (FAC), and STE-RVGLS were significant univariate predictors of overall and cardiac death. In multivariate Cox regression, age, ischemic etiology, diabetes, New York Heart Association functional class III to IV, and beta-blocker treatment were independent clinical predictors of overall mortality. CMR-RVEF (chi-square to enter = 3.9; p < 0.05), FT-RVGLS (chi-square to enter 3.7; p = 0.05), FAC (chi-square to enter 6.2; p = 0.02), and TAPSE (chi-square to enter = 4.1; p = 0.04) provided additional prognostic value over these baseline parameters, but the additional predictive value of STE-RVGLS (chi-square to enter = 10.8; p < 0.001) was significantly (p < 0.05) higher than the other tests. Additional hazard ratio to predict overall mortality was 2.5 (95% confidence interval [CI]: 1.6 to 3.9) for STE-RVGLS <-19%, 2.15 (95% CI: 1.34 to 3.43) for TAPSE >15 mm, 1.6 (95% CI: 1.02 to 2.49) for FAC >39%, 1.93 (95% CI: 1.25 to 2.99) for RVEF >41%, and 1.87 (95% CI: 1.10 to 3.19) for CMR-FT-RVGLS <-15%. CONCLUSIONS: 2D RVGLS provides strong additional prognostic value to predict overall and CV mortality in HFrEF, with higher predictive value than CMR-RVEF, CMR-FT-RVGLS, TAPSE, or FAC. This supports use of STE-RVGLS to identify higher-risk HFrEF patients.

Head-to-Head Comparison of Global and Regional Two-Dimensional Speckle Tracking Strain Versus Cardiac Magnetic Resonance Tagging in a Multicenter Validation Study.

BACKGROUND: Despite widespread use to characterize and refine prognosis, validation data of two-dimensional (2D) speckle tracking (2DST) echocardiography myocardial strain measurement remain scarce. METHODS AND RESULTS: Global and regional subendocardial peak-systolic Lagrangian longitudinal (LS) and circumferential strain (CS) by 2DST and 2D-tagged (2DTagg) cardiac magnetic resonance imaging were compared against sonomicrometry in a dynamic heart phantom and among each other in 136 patients included prospectively at 2 centers. The ability of regional LS and CS 2DST and 2DTagg to identify late gadolinium enhancement was compared using receiver operating characteristics curves. In vitro, both LS-2DST and 2DTagg highly agreed with sonomicrometry (intraclass correlation coefficient [ICC], 0.89 and ICC, 0.90, both P<0.001 with -3±2.8% and 0.34±4.35% bias, respectively). In patients, both global LS and global CS 2DST agreed well with 2DTagg (ICC, 0.89 and ICC, 0.80; P<0.001); however, they provided systematically greater values (relative bias of -37±27% and -25±37% for global LS and global CS, respectively). On regional basis, however, ICC (from 0.17 to 0.81) and relative bias (from -9 to -98%) between 2DST and 2DTagg varied strongly among segments. Ability to discriminate infarcted versus noninfarcted segments by late gadolinium enhancement was similarly good for regional LS 2DTagg and 2DST (area under the curve, 0.66 versus 0.59; P=0.08), while it was lower for CS 2DST than 2DTagg (area under the curve, 0.61 versus 0.75; P<0.001). CONCLUSIONS: The high accuracy against sonomicrometry and good agreement of global LS and global CS by 2DST and 2DTagg confirm the overall validity of 2DST strain measurement. Yet, higher intertechnique segmental variability and lower ability for detecting infarct suggest that 2DST strain estimates may be less performant on regional than on global basis.

Head-to-Head Comparison of Inflammation and Neovascularization in Human Carotid Plaques: Implications for the Imaging of Vulnerable Plaques.

BACKGROUND: Inflammation and intraplaque neovascularization are acknowledged to be 2 features of plaque vulnerability, although their temporal expression and their respective value in predicting clinical events are poorly understood. To determine their respective temporal associations, we conducted a comprehensive assessment of inflammation and intraplaque neovascularization in the carotid plaque of symptomatic and asymptomatic patients. METHODS AND RESULTS: Thirty patients with severe carotid stenosis underwent 18F-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging. Plaque 18F-fluorodeoxyglucose-uptake, indicative of inflammation, was measured by calculating the target:background ratio. The presence of intraplaque neovascularization during contrast-enhanced ultrasound was judged semiquantitatively; low-grade contrast enhancement (CE) suggested its absence, and high-grade CE, the presence of neovascularization. Carotid surgery was performed 1.6±1.8 days after completing both imaging modalities in all patients, and the presence of macrophages and neovessels was quantified by immunohistochemistry. We identified a significant correlation between the target:background ratio and macrophage quantification (R=0.78; P<0.001). The number of vessels was also significantly higher in carotid plaque with high-CE (P<0.001). Surprisingly, immunohistochemistry showed that high-CE and vessel number were neither associated with an elevated target:background ratio (P=0.28 and P=0.60, respectively) nor macrophage infiltration (P=0.59 and P=0.40, respectively). Finally, macrophage infiltration and target:background ratio were higher in the carotid plaque of symptomatic patients (P=0.021 and P=0.05, respectively), whereas CE grade and the presence of neovessels were not. CONCLUSIONS: Inflammation and intraplaque neovascularization are not systematically associated in carotid plaques, suggesting a temporal separation between the 2 processes. Inflammation seems more pronounced when symptoms are present. These data highlight the challenges that face any imaging strategy designed to assess plaque vulnerability.

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.

A randomized trial on the optimization of 18F-FDG myocardial uptake suppression: implications for vulnerable coronary plaque imaging.

UNLABELLED: (18)F-FDG PET/CT can be used to detect arterial atherosclerotic plaque inflammation. However, avid myocardial glucose uptake may preclude its use for visualizing coronary plaques. Fatty acid loading or calcium channel blockers could decrease myocardial (18)F-FDG uptake, thus assisting coronary plaque inflammation identification. The present prospective randomized trial compared the efficacies of different interventions for suppressing myocardial (18)F-FDG uptake. We also investigated whether circulating free fatty acid (cFFA) levels predicted the magnitude of myocardial (18)F-FDG uptake. METHODS: Thirty-six volunteers ate a high-fat low-carbohydrate meal, followed by a 12-h fasting period. They were then randomized to 1 of 4 intervention groups. Group 1 received no additional preparation and served as a reference. Groups 2 and 3, respectively, received a commercial high-fat solution containing 43.8 g of lipids or 50 mL of olive oil 1 h before (18)F-FDG injection to evaluate the impact of fatty acid loading on myocardial (18)F-FDG uptake. Group 4 received verapamil to evaluate the effect of calcium channel blockers. Cardiac PET/CT was performed after administration of 370 MBq of (18)F-FDG. Myocardial uptake suppression was assessed using a qualitative visual scale and by measuring the myocardial maximum standardized uptake value (SUV(max)). Insulin, glucose, and cFFA were serially measured. RESULTS: The qualitative visual scale showed good myocardial (18)F-FDG uptake suppression in 8 of 9, 5 of 9, 4 of 9, and 8 of 9 subjects of groups 1, 2, 3, and 4, respectively (P = 0.09). SUV(max) did not significantly differ between groups (P = 0.17). Interestingly, cFFA levels were higher in volunteers with good suppression (0.80 ± 0.31 mmol/L) than in those with poor suppression (0.53 ± 0.15 mmol/L; P = 0.011). We found an inverse correlation between cFFA level (measured at (18)F-FDG injection) and the SUV(max) (R = 0.61). Receiver-operating-characteristic curve analysis identified 0.65 mmol/L cFFA as the best cutoff value to predict adequate (18)F-FDG uptake suppression (positive predictive value, 89%). CONCLUSION: A high-fat low-carbohydrate meal followed by a 12-h fasting period effectively suppressed myocardial (18)F-FDG uptake in most subjects. Neither complementary fatty acid loading nor verapamil administered 1 h before (18)F-FDG injection conferred any additional benefit. Myocardial (18)F-FDG uptake was inversely correlated with cFFA level, representing an interesting way to predict myocardial (18)F-FDG uptake suppression.

Valve repair improves the outcome of surgery for chronic severe aortic regurgitation: a propensity score analysis.

BACKGROUND: For patients with aortic regurgitation (AR), aortic valve (AV) repair represents an attractive alternative to AV replacement (AVR), because it does not expose patients to the risk of prosthetic valve complications. Although the durability of AV repair has been documented, its prognosis has not yet been compared with prognosis of AVR. METHODS: We performed a propensity score analysis to match patients who underwent surgical correction of severe AR by either AVR or AV repair between 1995 and 2012. After matching, 44 pairs of patients were compared regarding baseline characteristics; overall survival; operative survival; cardiac events, including reoperations; recurrent AR; and New York Heart Association functional class at final follow-up. RESULTS: Operative mortality was similar in the AV repair and AVR groups (2% vs 5%; P=.56). Kaplan-Meier survival analysis indicated a significantly better overall 9-year survival after AV repair than after AVR (87% vs 60%; P=.007). Cox proportional survival analysis demonstrated that the choice of treatment was an independent predictor of postoperative survival. Finally, AV repair resulted in a slight increase, albeit not statistically significant, in reoperation rate (8% vs 2%; log rank P=.35). CONCLUSIONS: AV repair significantly improves postoperative outcomes in patients with AR and whenever feasible should probably be the preferred mode of surgical correction.

Prognostic value of myocardial viability by delayed-enhanced magnetic resonance in patients with coronary artery disease and low ejection fraction: impact of revascularization therapy.

OBJECTIVES: The purpose of this study was to evaluate the impact of myocardial viability assessment by delayed-enhanced cardiac magnetic resonance (DE-CMR) and of revascularization therapy on survival in patients with coronary artery disease (CAD) and low ejection fraction (EF). BACKGROUND: Prior studies have shown that DE-CMR predicts recovery of left ventricular (LV) dysfunction after revascularization. METHODS: The authors prospectively evaluated survival of 144 consecutive patients (130 males, age 65 ± 11 years) with CAD and LV dysfunction (EF: 24 ± 7%) undergoing DE-CMR. Eighty-six patients underwent complete revascularization of dysfunctional myocardium (79 coronary artery bypass grafting, 7 percutaneous coronary intervention), whereas 58 patients remained under medical treatment. RESULTS: Over the 3-year median follow-up, 49 patients died. Three-year survival was significantly worse in medically treated patients with dysfunctional viable than with nonviable myocardium (48% vs. 77% survival, p = 0.02). By contrast, in revascularized patients, survival was similar whether myocardium was viable or not (88% and 71% survival, respectively, p = NS). Hazard of death of viable myocardium remaining under medical treatment versus complete revascularization was 4.56 (95% confidence interval [CI]: 1.93 to 10.8). Cox multivariate analysis indicated that interaction of revascularization and viability provided significant additional value (chi-square test = 13.1, p = 0.004) to baseline predictors of survival (New York Heart Association functional class, wall motion score, and peripheral artery disease). More importantly, in 43 pairs of propensity score-matched patients, hazard of death (hazard ratio: 2.5 [95% CI: 1.1 to 6.1], p = 0.02) remained significantly higher for medically treated patients rather than for those with fully revascularized viable myocardium. CONCLUSIONS: Without revascularization, presence of dysfunctional viable myocardium by DE-CMR is an independent predictor of mortality in patients with ischemic LV dysfunction. This observation may be useful for pre-operative selection of patients for revascularization.

Imaging the vulnerable plaque.

Cardiovascular diseases are still the primary causes of mortality in the United States and in Western Europe. Arterial thrombosis is triggered by a ruptured atherosclerotic plaque and precipitates an acute vascular event, which is responsible for the high mortality rate. These rupture-prone plaques are called "vulnerable plaques." During the past decades, much effort has been put toward accurately detecting the presence of vulnerable plaques with different imaging techniques. In this review, we provide an overview of the currently available invasive and noninvasive imaging modalities used to detect vulnerable plaques. We will discuss the upcoming challenges in translating these techniques into clinical practice and in assigning them their exact place in the decision-making process.

Detection and quantification of myocardial scars by contrast-enhanced 3D echocardiography.

BACKGROUND: Myocardial infarct scars are usually imaged by delayed-enhanced cardiac magnetic resonance (DE-cMR). In this study, we tested the hypothesis that the detection and quantification of myocardial scars can be evaluated by 3D echocardiography (3D-echo). METHODS AND RESULTS: Fifty patients with a healed myocardial infarction (>3 months) and 10 controls underwent 3D echo and DE-cMR within 2 weeks. 3D-echo images were acquired with different settings, with or without contrast. The highest contrast-to-noise ratio was obtained with second-harmonic imaging (1.6/3.2 MHz), at a mechanical index of 0.5, in the presence of contrast. Using this modality, we calculated the sensitivity and specificity of the 3D-echo detection of cMR scars on a segmental basis to be 78% and 99%, respectively. On a per-patient basis, they were 96% and 90%, respectively. Good correlation and limits of agreement were found between the assessment of scar mass by 3D echo and DE-cMR (r=0.93, P<0.001; bias, 1.4+/-3.6 g), and the concordance between both techniques for the assessment of scar transmurality was good. Intraobserver, interobserver, and day-to-day reproducibility was comparable between 3D echo and DE-cMR for both the detection and quantification of scars. CONCLUSIONS: Contrast-enhanced 3D echo is a promising new tool for the detection and quantification of myocardial infarct scars.

Mechanisms of recurrent aortic regurgitation after aortic valve repair: predictive value of intraoperative transesophageal echocardiography.

OBJECTIVES: The aim of the present study was to examine the intraoperative echocardiographic features associated with recurrent severe aortic regurgitation (AR) after an aortic valve repair surgery. BACKGROUND: Surgical valve repair for AR has significant advantages over valve replacement, but little is known about the predictors and mechanisms of its failure. METHODS: We blindly reviewed all clinical, pre-operative, intraoperative, and follow-up transesophageal echocardiographic data of 186 consecutive patients who underwent valve repair for AR during a 10-year period and in whom intraoperative and follow-up echo data were available. After a median follow-up duration of 18 months, 41 patients had recurrent 3+ AR, 23 patients presented with residual 1+ to 2+ AR, and 122 had no or trivial AR. In patients with recurrent 3+ AR, the cause of recurrent AR was the rupture of a pericardial patch in 3 patients, a residual cusp prolapse in 26 patients, a restrictive cusp motion in 9 patients, an aortic dissection in 2 patients, and an infective endocarditis in 1 patient. RESULTS: Pre-operatively, all 3 groups were similar for aortic root dimensions and prevalence of bicuspid valve (overall 37%). Patients with recurrent AR were more likely to display Marfan syndrome or type 3 dysfunction pre-operatively. At the opposite end, patients with continent AR repair at follow-up were more likely to have type 2 dysfunction pre-operatively. After cardiopulmonary bypass, a shorter coaptation length, the degree of cusp billowing, a lower level of coaptation (relative to the annulus), a larger diameter of the aortic annulus and the sino-tubular junction, the presence of a residual AR, and the width of its vena contracta were associated with the presence of AR at follow-up. Multivariate Cox analysis identified a shorter coaptation length (odds ratio [OR]: 0.8, p = 0.05), a coaptation occurring below the level of the aortic annulus (OR: 7.9, p < 0.01), a larger aortic annulus (OR: 1.2, p = 0.01), and residual aortic regurgitation (OR: 5.3, p = 0.01) as risk factors of repair failure. CONCLUSIONS: Our results demonstrate that intraoperative transesophageal echocardiography can be used to identify patients undergoing AR repair who are at increased risk for late repair failure.

Early hazards of mitral ring annuloplasty in patients with moderate to severe ischemic mitral regurgitation undergoing coronary revascularization: the importance of preoperative myocardial viability.

BACKGROUND AND AIM OF THE STUDY: The impact of adding mitral ring annuloplasty (MRA) to coronary bypass grafting (CABG) in patients with ischemic mitral regurgitation (iMR) is unclear. The study aim was to compare the 30-day and four-year survival of patients with moderate to severe iMR undergoing CABG or CABG+MRA, and to investigate the role of contractile reserve (CR) in the prognostic response to MRA. METHODS: A total of 76 coronary patients (61 men, 15 women; mean age 62 +/- 9 years) with poor left ventricular ejection fraction (LVEF) of 33 +/- 11% and grade > or =2 iMR underwent low-dose dobutamine echocardiography to identify their CR before CABG. The survival of 34 patients undergoing CABG+MRA was compared to that of 42 patients who underwent CABG alone. The groups were further substratified according to their preoperative CR. RESULTS: During follow up, 24 patients died from cardiac causes, and two others required heart transplantation. At one year, the residual iMR and NYHA functional class were lower in patients undergoing MRA than in those that did not. The 30-day and four-year survivals were lower in patients undergoing MRA in the absence of CR than in the other patients (71 +/- 11% versus 95 +/- 3% at 30 days, p = 0.002; 35 +/- 11% versus 69 +/- 6% at four years, p = 0.008). Cox's proportional hazard analysis identified CR (HR = 0.14, 95% CI 0.05-0.38, p < 0.001), MRA (HR = 3.54, 95% CI 1.48-8.50, p = 0.004), additive EuroSCORE (HR = 1.29, 95% CI 1.08-1.55, p = 0.006) and LVEF (HR = 0.93, 95% CI 0.59-0.98, p = 0.001) as independent predictors of long-term outcome in this population. CONCLUSION: In patients with moderate to severe iMR, survival after CABG is mainly influenced by the presence of CR. By contrast, adding MRA to CABG does not affect long-term survival, except in patients without CR, in whom it increases early mortality.

Flow-function relationships in chronic left-ventricular ischemic dysfunction: Impact of the transmurality of infarction.

BACKGROUND: We examined flow-function relationships in humans with chronic coronary artery disease (CAD) in relation to the transmural extent of necrosis, aiming to distinguish the various pathophysiologic conditions that cause chronic ischemic dysfunction, ie, chronic hibernation (perfusion-contraction match) from chronic stunning (perfusion-contraction mismatch). METHODS AND RESULTS: Twenty-two patients (18 men, 61 +/- 13 years) with CAD and chronic contractile dysfunction (ejection fraction, 26% +/- 13%) and 6 volunteers underwent tagged and gadolinium (Gd)-DTPA contrast-enhanced magnetic resonance imaging as well as (13)NH(3)-positron emission tomography. The relationship between regional circumferential shortening strain (ECC), transmural necrosis, and absolute transmural myocardial perfusion (MBF) was examined quantitatively in dysfunctional segments (<10% ECC). Noninfarcted (<25% transmurality), dysfunctional myocardium presented a perfusion-contraction mismatch, as indicated by a 72% reduction (to -5% +/- 4% shortening) of ECC, versus only a 12% (to 63 +/- 20 mL/min/100 g) reduction of transmural MBF. With increasing amounts of necrosis, reductions between perfusion versus contraction became increasingly matched, ie, dysfunctional segments with a greater than 75% transmural extent of necrosis had a 57% reduction of MBF (to 30 +/- 17 mL/min/100 g), for a similar severe reduction of 80% of ECC (to -3% +/- 3% shortening). CONCLUSIONS: Noninfarcted, dysfunctional human myocardium mostly presents with a perfusion-contraction mismatch, consistent with stunning. By contrast, dysfunctional myocardium presenting with a perfusion-contraction match is always associated with significant amounts of necrosis.

Chronic ischemic left ventricular dysfunction: from pathophysiology to imaging and its integration into clinical practice.

Chronic ischemic left ventricular dysfunction is present in a number of clinical syndromes in which myocardial revascularization results in an improvement of left ventricular function, patients' functional class, and their survival. Early diagnosis of and treatment of viability is essential. Coronary arteriography is of limited value in diagnosis of viability. Noninvasive testing is essential for diagnosis, which can be matched to the pathophysiologic changes that occur in hibernating myocardium. However, no single test has a perfect, or near perfect, sensitivity and specificity, and thus, a combination of tests are usually needed. Algorithms are developed to integrate these tests in clinical decision making.