Sphingolipid Metabolism Is Associated with Cardiac Dyssynchrony in Patients with Acute Myocardial Infarction.

AIM: Sphingolipids are a class of complex and bioactive lipids that are involved in the pathological processes of cardiovascular disease. Fabry disease is an X-linked storage disorder that results in the pathological accumulation of glycosphingolipids in body fluids and the heart. Cardiac dyssynchrony is observed in patients with Fabry disease and left ventricular (LV) hypertrophy. However, little information is available on the relationship between plasma sphingolipid metabolites and LV remodelling after acute myocardial infarction (AMI). The purpose of this study was to assess whether the baseline plasma sphingomyelin/acid ceramidase (aCD) ratio predicts LV dyssynchrony at 6M after AMI. METHODS: A total of 62 patients with AMI undergoing primary angioplasty were recruited. Plasma aCD and sphingomyelin were measured prior to primary angioplasty. Three-dimensional echocardiographic measurements of the systolic dyssynchrony index (SDI) were performed at baseline and 6 months of follow-up. The patients were divided into three groups according to the level of aCD and sphingomyelin above or below the median. Group 1 denotes lower aCD and lower sphingomyelin; Group 3 denotes higher aCD and higher sphingomyelin. Group 2 represents different categories of patients with aCD and sphingomyelin. Trend analysis showed a significant increase in the SDI from Group 1 to Group 3. Logistic regression analysis showed that the sphingomyelin/aCD ratio was a significant predictor of a worsening SDI at 6 months. CONCLUSIONS: AMI patients with high baseline plasma sphingomyelin/aCD ratios had a significantly increased SDI at six months. The sphingomyelin/aCD ratio can be considered as a surrogate marker of plasma ceramide load or inefficient ceramide metabolism. Plasma sphingolipid pathway metabolism may be a new biomarker for therapeutic intervention to prevent adverse remodelling after MI.

Comparison of left ventricular subclinical systolic dysfunction between hemodialysis patients and renal transplant recipients using real time three-dimensional echocardiography.

AIMS: The relationship between chronic kidney disease and development of heart failure is a well-known clinical entity. Systolic dyssynchrony index (SDI_16) is a new diagnostic tool for detection of subclinical left ventricular (LV) systolic dysfunction by using three-dimensional echocardiography (3DE). We aimed to investigate this parameter in patients with end-stage renal disease who were receiving hemodialysis and patients with renal transplant compared to healthy control subjects. MATERIAL AND METHODS: Forty-five hemodialysis patients, 45 patients with renal transplant and 45 age-sex matched healthy control subjects included in the study. All participants were evaluated with 3DE in the interdialytic phase for measurement of LV volumes, ejection fraction and SDI_16 parameter. RESULTS: Both LV diastolic and systolic volumes were significantly higher in hemodialysis group compared to renal transplant group and healthy controls, but this finding did not translate to a statistically significant difference for LVEF measurements between groups (58.71 ± 3.53 vs. 57.17 ± 2.97 vs. 59.23 ± 3.26, p = .16 for renal transplant and hemodialysis and healthy control groups, respectively). Mean value of SDI_16 parameters was significantly higher in hemodialysis group compared to renal transplant group (7.93 ± 2.50 vs. 3.72 ± 1.71, p < .001) and healthy controls (7.93 ± 2.50 vs. 3.00 ± .99, p < .001); whereas, it was similar between renal transplant group and control subjects (3.72 ± 1.71 vs. 3.00 ± .99, p = .10). CONCLUSION: SDI_16 was significantly higher in hemodialysis patients compared to patients with renal transplant and healthy controls.

Real-time three-dimensional echocardiography for detection of cardiac sarcoidosis in the early stage: a cross-sectional single-centre study.

BACKGROUND: Sarcoidosis with cardiac involvement has a relatively high morbidity and mortality, and early diagnose of cardiac sarcoidosis is a critical issue. Systolic dyssynchrony index (SDI) measured by three-dimensional echocardiography was used in our study for detection of subclinical left ventricular (LV) systolic dysfunction in patients with sarcoidosis and normal LV function on two-dimensional echocardiography. METHODS: Forty-four patients diagnosed with sarcoidosis (without clinically apparent cardiac involvement) and 44 healthy control subjects were included in this study. Two-dimensional echocardiographic parameters, also LV volumes and SDI measured by 3D echocardiography were analyzed in all participants. RESULTS: While two-dimensional echocardiographic results of both study groups were similar; SDI_16 (SDI for 16 segments of LV) results were significantly higher in sarcoidosis group compared to healthy controls (6.99 ±5.02 vs 2.89 ± 1.32, p < 0.0001). CONCLUSION: SDI_16 was higher in patients with sarcoidosis compared to healthy controls probably due to patchy infiltration characteristic of the disease. This parameter could be used as a marker to identify patients with cardiac involvement of sarcoidosis in the early phase.

Left ventricular systolic dyssynchrony index and endothelial dysfunction parameters as subclinical predictors of cardiovascular involvement in patients with beta-thalassemia major.

OBJECTIVE: Cardiovascular iron load is the leading cause of morbidity and mortality in beta-thalassemia major (ß-TM). However, many patients remain asymptomatic until the late stage. In this cross-sectional study, we investigated the role of three-dimensional (3D) echocardiography and endothelial dysfunction parameters in asymptomatic ß-TM patients, and the relationship between these parameters and cardiac magnetic resonance imaging (MRI) T2* value. METHODS: A total of 51 asymptomatic ß-TM patients receiving regular blood transfusions were divided into two groups based on cardiac MRI-T2* values (MRI-T2*<20 ms and ≥20 ms), which MRI-T2*<20 ms determines myocardial iron load and evaluated by two-dimensional (2D) and 3D-echocardiography including endothelial dysfunction parameters. The relationships between ferritin levels, 2D and 3D-echocardiography measurements, endothelial dysfunction parameters, and cardiac MRI-T2* values were investigated. RESULTS: All left ventricle ejection fraction (LVEF) obtained by 2D-echocardiography were normal (≥50%). LVEF-3D (53.25 ± 2.33 vs. 58.81 + 1.02), SDI12 (6.53 ± 0.56 vs. 2.85 + 0.48), and SDI16 (7.65 ± 0.75 vs. 3.26 + 0.49) were significantly different and negatively correlated between groups with MRI-T2*<20 ms and ≥20 ms, respectively. Flow-mediated dilatation (FMD) (6.08% ± 0.34% vs. 14.46% ± 1.12), aortic strain (7.79% ± 2.19% vs. 12.76% ± 4.19), ferritin levels were significantly different and negatively correlated between groups with MRI-T2*<20 ms and ≥20 ms, respectively. Higher ferritin, SDI12/16 were significant independent predictors of MR-T2* < 20 ms. SDI16 > 5.5, SDI12 > 4.3 predicted MRI-T2*<20ms with a sensitivity of 92%, specificity of 81% (AUC 0.85, P < .001), and sensitivity of 92%, specificity of 78% (AUC 0.83, P < .001), respectively. CONCLUSION: SDI12/16 calculated by 3D-echocardiography may be a promising predictors of cardiovascular iron load and, decreased LVEF-3D, FMD, and aortic strain might be good indicators of subclinical cardiovascular involvement of ß-TM.

Cardiac resynchronisation therapy optimisation of interventricular delay by the systolic dyssynchrony index: A comparative, randomised, 12-month follow-up study.

BACKGROUND: The aim of our study was to compare the effect of interventricular (VV) delay optimisation in CRT recipients on the basis of systolic dyssynchrony index (SDI) derived from the three-dimensional echocardiography (3DE) versus QRS width assessment on left ventricle volume reduction at the 12-month follow-up. METHODS: We included 63 patients with recently implanted CRT in this randomised, open-label trial. Patients were randomised to VV delay optimisation according to QRS complex width measurement in group 1 (n = 31) to obtain the narrowest QRS complex and SDI in group 2 (n = 32) to achieve its lowest possible value. We evaluated left ventricular end-systolic volume (LVESv), left ventricular ejection fraction (LVEF) and SDI by 3DE before CRT implantation and at a 12-month follow-up in all the patients. We also obtained the New York Heart Association functional class, the 6-minute walk test, the quality of life questionnaire and the level of NT-proBNP. RESULTS: The number of volumetric responders was similar in both groups (17 vs. 20, P = 0.786). There were also no significant differences in the reduction of LVESv (-41 ± 55 mL vs. - 61 ± 51 mL, P = 0.111), improvement in LVEF (+10.1 ± 10.6% vs. + 13.0 ± 9.9%, P = 0.213) or differences in clinical outcomes between both groups at the 12-month follow-up. CONCLUSION: CRT optimisation of interventricular delay using SDI compared with QRS width assessment did not reveal any significant difference in terms of volumetric and clinical response at the 12-month follow-up.

The impact of multipole pacing on left ventricular function in patients with cardiac resynchronization therapy - A real-time three-dimensional echocardiography approach.

BACKGROUND: Cardiac resynchronization therapy (CRT) is standard of care in heart failure (HF), however this technique is associated with a non-responder rate of 30%. Multipole pacing (MPP) with a quadripolar lead may optimize CRT and responder rate by creating two electrical wave fronts in the left ventricular (LV) myocardium simultaneously in order to reduce mechanical dyssynchrony. The objective of this study was to investigate the acute impact of MPP on LV function by assessing systolic dyssynchrony index (SDI) and left ventricular ejection fraction (LVEF) via real-time three-dimensional echocardiography (RT3DE). METHODS: In 41 consecutive patients (87.8% male; mean age 66.0 ±â€¯12.7 years) who received CRT defibrillators with a quadripolar LV lead, RT3DE datasets were acquired the day after implantation under the following pacing configurations: Baseline AAI, conventional biventricular pacing using distal or proximal LV poles and MPP. Datasets were analyzed in paired samples evaluating SDI and LVEF depending on programmed pacing modality. RESULTS: MPP resulted in statistically significant reduction of SDI compared to baseline (6.3%; IQR 4.4-7.8 and 9.9%; IQR 8.0-12.7; p < 0.001) and to conventional biventricular pacing using distal (7.6%; IQR 6.5-9.1; p < 0.001) or proximal (7.4%; IQR 6.2-8.8; p < 0.001) LV poles respectively. MPP yielded significant increase in LVEF compared to baseline (30.6%; IQR 25.8-37.5 and 27.2%; IQR 21.1-33.6; p < 0.001) and to conventional biventricular pacing configuration with distal (28.1%; IQR 22.1-34.5; p < 0.001) or proximal (28.6%; IQR 23.2-34.9; p < 0.001) LV poles respectively. CONCLUSIONS: Multipole pacing improves mechanical dyssynchrony of the left ventricular myocardium as assessed by SDI and LVEF.

Three-dimensional echocardiographic evaluation of mechanical dyssynchrony in systolic heart failure with narrow QRS complex.

OBJECTIVES: To investigate the role of three-dimensional echocardiography (3DE) in evaluation of left ventricular mechanical dyssynchrony (LVMD) in heart failure (HF) patients with narrow QRS. METHODS: 143 subjects (70 with HF and narrow QRS, 23 with HF and LBBB and 50 controls) were subjected to 3DE, evaluating global and regional dyssynchrony using systolic dyssynchrony index, maximum segmental dyssynchrony and opposite segment dyssynchrony. Spatial distribution of LVMD was studied in each patient using 3DE derived regional time volume curves. Extent of LVMD in HF patients with narrow QRS was compared to those with left bundle branch block (LBBB). RESULTS: Frequency of LVMD was similar in HF patients with narrow QRS or LBBB (55.7% vs. 47.8%, p=NS). There was no difference in the severity of LVMD between these two groups (10.7±6.7% vs. 12.1±7.4%, p=NS). Both HF groups had significantly more dyssynchrony than controls. A scattered pattern of distribution of asynchronous segments was seen in narrow QRS patients; 33.96% of them had their earliest contracting segment, instead of delayed segment, located in areas conventionally targeted for LV pacing i.e. anterolateral, inferolateral or inferior segments. CONCLUSIONS: 3DE confirmed significant dyssynchrony in >50% HF patients with narrow QRS as demonstrated by other imaging methods. 3D distribution patterns of asynchronous segments indicate possibility of left ventricular mechanics related reasons responsible for lack of CRT responsiveness, an observation that generates hypothesis on possible reasons of CRT non-responsiveness.

Assessment of left ventricular dyssynchrony by three-dimensional echocardiography: Prognostic value in patients undergoing cardiac resynchronization therapy.

BACKGROUND: Systolic dyssynchrony index (SDI) using three-dimensional echocardiography (3DE) was shown to be a reliable measure of left ventricular (LV) dyssynchrony. However, the prognostic value of SDI on long-term outcomes after cardiac resynchronization therapy (CRT) remains unknown. METHODS AND RESULTS: A total of 414 patients (mean age 67 ± 10 years, 60% ischemic etiology) with 3DE evaluation before CRT implantation were included. SDI was evaluated as continuous value and in quartiles. The study endpoint was combined all-cause mortality, heart transplantation, and LV assist device implantation. At baseline, median SDI was 8.0% (IQR 5.6-11.3%). During a median follow-up of 45 months (IQR 25-59 months), the endpoint was observed in 94 (23%) patients. SDI was independently associated with the endpoint together with ischemic etiology, diabetes, and renal function (HR 0.914, P = 0.003) after adjustment for age, atrial fibrillation, hemoglobin level, NYHA functional class, and posterolateral LV lead position. Patients from the 1st, 2nd, and 3rd SDI quartiles showed similar survival and superior as compared to the 4th quartile with the lowest SDI values (≤5.5%; χ²: 30.4, log-rank P < 0.001). From receiver operating characteristic curve analysis, the optimal SDI cut-off value associated with the endpoint was >6.8% (area under the curve 0.634). Finally, a subgroup analysis (293 patients) demonstrated that a more pronounced reduction in SDI immediately after CRT (resynchronization) was independently associated with superior survival (HR 0.461, P = 0.011) after adjustment for prognostic relevant parameters. CONCLUSION: SDI is independently associated with long-term prognosis after CRT and might therefore be important to optimize risk-stratification in these patients.

Do we overestimate left ventricular ejection fraction by two-dimensional echocardiography in patients with left bundle branch block?

AIMS: Left bundle branch block (LBBB) causes a dyssynchronized contraction of left ventricle. This is a kind of regional wall-motion abnormality and measuring left ventricular ejection fraction (LVEF) by two-dimensional (2D) echocardiography could be less reliable in this particular condition. Our aim was to evaluate the role of dyssynchrony index (SDI), measured by three-dimensional (3D) echocardiography, in assessment of LVEF and left ventricular volumes accurately in patients with LBBB. METHODS AND RESULTS: In this case-control study, we included 52 of 64 enrolled participants (twelve participants with poor image quality were excluded) with LBBB and normal LVEF or nonischemic cardiomyopathy. Left ventricular ejection fraction (LVEF) and left ventricular volumes were assessed by 2D (modified Simpson's rule) and 3D (four beats full volume analysis) echocardiography and the impact of SDI on results were evaluated. In patients with SDI ≥6%, LVEF measurements were significantly different (46.00% [29.50-52.50] vs 37.60% [24.70-45.15], P < .001) between 2D and 3D echocardiography, respectively. In patients with SDI < 6%, there were no significant differences between two modalities in terms of LVEF measurements (54.50% [49.00-59.00] vs 54.25% [40.00-58.25], P = .193). LV diastolic volumes were not significantly different while systolic volumes were underestimated by 2D echocardiography, and this finding was more pronounced when SDI ≥ 6%. CONCLUSION: In patients with LBBB and high SDI (≥6%), LVEF values were overestimated and systolic volumes were underestimated by 2D echocardiography compared to 3D echocardiography.

Intraoperative assessment of transient and persistent regional left ventricular wall motion abnormalities in patients undergoing coronary revascularization surgery using real time three-dimensional transesophageal echocardiography: A prospective observational study.

OBJECTIVE: To evaluate the feasibility of intraoperative real time three-dimensional echocardiography (RT3DE) for identification and quantification of transient and persistent regional wall motion abnormalities (RWMAs) in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG). DESIGN: A prospective observational study SETTING: Single-center study in an academic tertiary care hospital PARTICIPANTS: A series of 42 patients undergoing elective CABG over a 2-year period were included. INTERVENTION: After induction of anesthesia, a comprehensive transesophageal echocardiography (TEE) examination was performed to evaluate regional wall motion using two-dimensional wall motion score index (WMSI) and RT3D echocardiographic parameters at three specific time points during the operative phase. MEASUREMENTS AND MAIN RESULTS: The 3D assessment of LV function was based on the quantification of change in LV chamber volume over time from each segment excursion. Patients were divided into two groups and subgroups based on TEE findings. There was significant mechanical dyssynchrony in patients with RWMAs (WMSI > 1; systolic dyssynchrony index [SDI] = 7.0 ± 3.66) as compared to the patients having normal wall motion (WMSI = 1; SDI = 2.0 ± 0.95; P = .001). Patients with contractile dysfunction were found to have low values of segmental excursion and high values of negative excursion on parametric imaging. Persistent RWMAs due to hibernating myocardium showed significant resolution of mechanical dyssynchrony after revascularization. Parametric imaging could detect transient RWMAs due to stunning and graft dysfunction. Early activating segments (EAS) on "timing bull's-eye" may represent hypercontractile segments and may influence inotrope administration. CONCLUSION: The RT3DE is a valuable modality for precise quantification of regional wall motion during revascularization procedure.

Quantitative assessment of left ventricular mechanical dyssynchrony using cine cardiovascular magnetic resonance imaging: Inter-study reproducibility.

OBJECTIVES: To determine the inter-study reproducibility of left ventricular (LV) mechanical dyssynchrony measures based on standard cardiovascular magnetic resonance (CMR) cine images. DESIGN: Steady-state free precession (SSFP) LV short-axis stacks and three long-axes were acquired on the same day at three time points. Circumferential strain systolic dyssynchrony indexes (SDI), area-SDI as well as circumferential and radial uniformity ratio estimates (CURE and RURE, respectively) were derived from CMR myocardial feature-tracking (CMR-FT) based on the tracking of three SSFP short-axis planes. Furthermore, 4D-LV-analysis based on SSFP short-axis stacks and longitudinal planes was performed to quantify 4D-volume-SDI. SETTING: A single-centre London teaching hospital. PARTICIPANTS: 16 healthy volunteers. MAIN OUTCOME MEASURES: Inter-study reproducibility between the repeated exams. RESULTS: CURE and RURE as well as 4D-volume-SDI showed good inter-study reproducibility (coefficient of variation [CoV] 6.4%-12.9%). Circumferential strain and area-SDI showed higher variability between the repeated measurements (CoV 24.9%-37.5%). Uniformity ratio estimates showed the lowest inter-study variability (CoV 6.4%-8.5%). CONCLUSIONS: Derivation of LV mechanical dyssynchrony measures from standard cine images is feasible using CMR-FT and 4D-LV-analysis tools. Uniformity ratio estimates and 4D-volume-SDI showed good inter-study reproducibility. Their clinical value should next be explored in patients who potentially benefit from cardiac resynchronization therapy.

Ventricular Twisting and Dyssynchrony in Children with Single Left Ventricle Using Three-Dimensional Speckle Tracking Imaging after the Fontan Operation.

BACKGROUND: The importance of left ventricular (LV) twisting has been recognized in various types of heart disease, but no studies have investigated twisting of functional single ventricle using echocardiography. This study aimed to evaluate LV twisting and dyssynchrony of children with single left ventricle (SLV) after the Fontan operation and explore the relationship between twisting motion and ventricular contractility using three-dimensional speckle tracking imaging (3DSTI). METHODS: Thirty-five children with SLV and 35 healthy children (controls) were enrolled. The patients were divided into wide and narrow QRS groups according to the QRS interval. Atrioventricular valve inflow velocity and tissue Doppler imaging velocity were obtained, and the Tei index was calculated. Apical rotation, basal rotation, twist, torsion, time to peak apical rotation, time to peak basal rotation, time to peak twist, apical-basal rotation delay, and the systolic dyssynchrony index (SDI) were measured by 3DSTI. RESULTS: Patients with SLV had significantly lower apical rotation (2.50 ± 2.25° vs. 4.85 ± 2.68°, P < 0.001), basal rotation (-3.46 ± 3.11° vs. -7.76 ± 2.11°, P < 0.001), twist (5.15 ± 4.75° vs. 12.19 ± 3.65°, P < 0.001), and torsion (1.04 ± 0.99°/cm vs. 2.37 ± 0.77°/cm, P < 0.001) compared to controls. Time to peak basal rotation, apical-basal rotation delay, and time to peak twist were significantly longer in patients. Apical rotation was significantly lower in the wide QRS group but similar in the narrow QRS group as compared to controls. Time to peak twist and apical-basal delay were significantly longer in the wide QRS group in contrast to the similar time in the narrow QRS group compared with controls. Among these twisting parameters, twist and torsion were most significantly correlated with left ventricular ejection fraction (LVEF), the Tei index, and SDI. Twist and age were significantly correlated. CONCLUSION: Twisting is reduced in children with SLV after the Fontan operation. Torsion is a good indicator of LV global function because of good reproducibility and its lack of association with age.

Method for aortic wall strain measurement with three-dimensional ultrasound speckle tracking and fitted finite element analysis.

BACKGROUND: Aortic wall strains are indicators of biomechanical changes of the aorta due to aging or progressing pathologies such as aortic aneurysm. We investigated the potential of time-resolved three-dimensional ultrasonography coupled with speckle-tracking algorithms and finite element analysis as a novel method for noninvasive in vivo assessment of aortic wall strain. METHODS: Three-dimensional volume datasets of 6 subjects without cardiovascular risk factors and 2 abdominal aortic aneurysms were acquired with a commercial real time three-dimensional echocardiography system. Longitudinal and circumferential strains were computed offline with high spatial resolution using a customized commercial speckle-tracking software and finite element analysis. Indices for spatial heterogeneity and systolic dyssynchrony were determined for healthy abdominal aortas and abdominal aneurysms. RESULTS: All examined aortic wall segments exhibited considerable heterogenous in-plane strain distributions. Higher spatial resolution of strain imaging resulted in the detection of significantly higher local peak strains (p ≤ 0.01). In comparison with healthy abdominal aortas, aneurysms showed reduced mean strains and increased spatial heterogeneity and more pronounced temporal dyssynchrony as well as delayed systole. CONCLUSIONS: Three-dimensional ultrasound speckle tracking enables the analysis of spatially highly resolved strain fields of the aortic wall and offers the potential to detect local aortic wall motion deformations and abnormalities. These data allow the definition of new indices by which the different biomechanical properties of healthy aortas and aortic aneurysms can be characterized.

New three-dimensional speckle-tracking echocardiography identifies global impairment of left ventricular mechanics with a high sensitivity in childhood cancer survivors.

BACKGROUND: The aim of this case-control study was to assess the usefulness of three-dimensional (3D) speckle-tracking echocardiography in the evaluation of global left ventricular (LV) myocardial performance in adolescent and adult survivors of childhood cancers. METHODS: Fifty-three anthracycline-treated survivors of childhood cancers (mean age, 18.6 ± 5.1 years) and 38 controls were studied. Three-dimensional speckle-tracking echocardiography was performed to assess LV 3D global and segmental strain, time to peak segmental 3D strain, LV torsion, and ejection fraction. LV systolic dyssynchrony index (SDI) was calculated as the percentage of the standard deviation of times to peak strain of the 16 segments divided by the RR interval. A global performance index (GPI) was calculated as (global 3D strain × torsion)/SDI. The area under the receiver operating characteristic curve was calculated to determine the capability of various echocardiographic indices to discriminate between patients and controls. RESULTS: Compared with controls, patients had significantly reduced LV global 3D strain (P < .001), torsion (P < .001), and GPI (P < .001) and greater SDI (P < .001). All except the basal anteroseptal segment in patients had reduced regional 3D strain compared with controls (P < .05 for all). Global 3D strain (P = .018), SDI (P = .003), and GPI (P = .02) were correlated with cumulative anthracycline dose. The areas under the curves for GPI, global 3D strain, 1/SDI, torsion, and ejection fraction were 0.92, 0.79, 0.79, 0.79, and 0.78, respectively. A GPI cutoff of 10.6°/cm had sensitivity of 84.9% and specificity of 81.6% of differentiating patients from controls. CONCLUSIONS: Three-dimensional speckle-tracking echocardiography enables the derivation of an index of LV global performance that incorporates LV 3D strain, dyssynchrony, and torsion for the sensitive detection of altered LV mechanics in childhood cancer survivors.