Tomoko Negishi

Reproducibility of Echocardiographic Techniques for Sequential Assessment of Left Ventricular Ejection Fraction and Volumes Application to Patients Undergoing Cancer Chemotherapy

OBJECTIVES The aim of this study was to identify the best echocardiographic method for sequential quantification of left ventricular (LV) ejection fraction (EF) and volumes in patients undergoing cancer chemotherapy. BACKGROUND Decisions regarding cancer therapy are based on temporal changes of EF. However the method for EF measurement with the lowest temporal variability is unknown. METHODS We selected patients in whom stable function in the face of chemotherapy for breast cancer was defined by stability of global longitudinal strain (GLS) at up to 5 time points (baseline, 3, 6, 9, and 12 months). In this way, changes in EF were considered to reflect temporal variability of measurements rather than cardiotoxicity. A comprehensive echocardiogram consisting of 2-dimensional (2D) and 3-dimensional (3D) acquisitions with and without contrast administration was performed at each time point. Stable LV function was defined as normal GLS (≤-16.0%) at each examination. The EF and volumes were measured with 2D-biplane Simpsons method, 2D-triplane, and 3-dimensional echocardiography (3DE) by 2 investigators blinded to any clinical data. Inter-, intra-, and test-retest variability were assessed in a subgroup. Variability was assessed by analysis of variance and compared with Levenes or t test. RESULTS Among 56 patients (all female, 54 ± 13 years of age), noncontrast 3D EF, end-diastolic volume, and end-systolic volume had significantly lower temporal variability than all other methods. Contrast only decreased the temporal variability of LV end-diastolic volume measurements by the 2D biplane method. Our data suggest that a temporal variability in EF of 0.06 might occur with noncontrast 3DE due to physiological differences and measurement variability, whereas this might be >0.10 with 2D methods. Overall, 3DE also had the best intra- and inter-observer as well as test-retest variability. CONCLUSIONS Noncontrast 3DE was the most reproducible technique for LVEF and LV volume measurements over 1 year of follow-up.

Clinical ResearchCardiac ImagingReproducibility of Echocardiographic Techniques for Sequential Assessment of Left Ventricular Ejection Fraction and Volumes: Application to Patients Undergoing Cancer Chemotherapy

OBJECTIVES The aim of this study was to identify the best echocardiographic method for sequential quantification of left ventricular (LV) ejection fraction (EF) and volumes in patients undergoing cancer chemotherapy. BACKGROUND Decisions regarding cancer therapy are based on temporal changes of EF. However the method for EF measurement with the lowest temporal variability is unknown. METHODS We selected patients in whom stable function in the face of chemotherapy for breast cancer was defined by stability of global longitudinal strain (GLS) at up to 5 time points (baseline, 3, 6, 9, and 12 months). In this way, changes in EF were considered to reflect temporal variability of measurements rather than cardiotoxicity. A comprehensive echocardiogram consisting of 2-dimensional (2D) and 3-dimensional (3D) acquisitions with and without contrast administration was performed at each time point. Stable LV function was defined as normal GLS (≤-16.0%) at each examination. The EF and volumes were measured with 2D-biplane Simpsons method, 2D-triplane, and 3-dimensional echocardiography (3DE) by 2 investigators blinded to any clinical data. Inter-, intra-, and test-retest variability were assessed in a subgroup. Variability was assessed by analysis of variance and compared with Levenes or t test. RESULTS Among 56 patients (all female, 54 ± 13 years of age), noncontrast 3D EF, end-diastolic volume, and end-systolic volume had significantly lower temporal variability than all other methods. Contrast only decreased the temporal variability of LV end-diastolic volume measurements by the 2D biplane method. Our data suggest that a temporal variability in EF of 0.06 might occur with noncontrast 3DE due to physiological differences and measurement variability, whereas this might be >0.10 with 2D methods. Overall, 3DE also had the best intra- and inter-observer as well as test-retest variability. CONCLUSIONS Noncontrast 3DE was the most reproducible technique for LVEF and LV volume measurements over 1 year of follow-up.

Use of speckle strain to assess left ventricular responses to cardiotoxic chemotherapy and cardioprotection

AIMS The variability of ejection fraction (EF) poses a problem in the assessment of left ventricular (LV) function in patients receiving potentially cardiotoxic chemotherapy. We sought to use global longitudinal strain (GLS) to compare LV responses to various cardiotoxic chemotherapy regimens and to examine the response to cardioprotection with beta-blockers (BB) in patients showing subclinical myocardial damage. METHODS AND RESULTS We studied 159 patients (49 ± 14 year, 127 women) receiving anthracycline (group A, n = 53, 46 ± 17 year), trastuzumab (group T, n = 61, 53 ± 12 year), or trastuzumab after anthracyclines (group AT, n = 45, 46 ± 9 year). LV indices [ejection fraction (EF), mitral annular systolic velocity, and GLS] were measured at baseline and follow-up (7 ± 7 months). Patients who decreased GLS by ≥11% were followed for another 6 months; initiation of BB was at the discretion of the clinician. Anthracycline dose was similar between group A and group AT (213 ± 118 vs. 216 ± 47 mg/m(2), P = 0.85). Although ΔEF was similar among the groups, attenuation of GLS was the greatest in group AT (group A, 0.7 ± 2.8% shortening; T, 1.1 ± 2.7%; and AT, 2.0 ± 2.3%; P = 0.003, after adjustment). Of 52 patients who decreased GLS by ≥-11%, 24 were treated with BB and 28 were not. GLS improved in BB groups (from -17.6 ± 2.3 to -19.8 ± 2.6%, P < 0.001) but not in non-BB groups (from -18.0 ± 2.0 to -19.0 ± 3.0%, P = 0.08). Effects of BB were similar with all regimens. CONCLUSIONS GLS is an effective parameter for identifying systolic dysfunction (which appears worst with combined anthracycline and trastuzumab therapy) and responds to cardioprotection in patients administered beta-blockers.

Practical guidance in echocardiographic assessment of global longitudinal strain

there has been increasing interest in the measurement of global myocardial strain because it is a sensitive and robust index to detect subclinical myocardial dysfunction, with a defined normal range [(1)][1]. Numerous commercially-available versions of speckle tracking software are available for

Role of Temporal Resolution in Selection of the Appropriate Strain Technique for Evaluation of Subclinical Myocardial Dysfunction

Objective: To assess the effects of frame and volume rate on the concordance between two‐dimensional speckle tracking strain (2DS) and three‐dimensional speckle tracking strain (3DS), and between 2DS and triplane imaging of speckle tracking (Tri‐P). Methods: Global longitudinal strains (GLSs) derived from 2DS, 3DS, and Tri‐P were compared among 142 prospectively recruited patients who underwent evaluation of subclinical left ventricle (LV) function. Results: Feasibility to obtain GLS of 3DS was significantly higher than that of Tri‐P (76% vs. 47%, P < 0.001). The correlation between 2DS and 3DS was only modest (r = 0.47) whereas that of 2DS and Tri‐P was better (r = 0.67). The difference in frame/volume rate between two methods also affected their correlation. A volume rate between 34 and 50 volumes/sec had the highest correlation between 2DS and 3DS (r = 0.72). The correlation between 2DS and Tri‐P was better with a difference in frame‐rate ≤20 per second than with a difference >20 per second. Likewise, there was a better correlation between 2DS and 3DS when the difference between 2D frame rate and 3D volume rate was ≤40 per second, compared to when it was >40 per second. These associations differed from segment to segment and the apical segments had the highest correlation and the basal the lowest. Conclusions: The feasibility of each means of strain calculation showed important differences, with 2DS being the most attainable. Strain values were not interchangeable among 2DS, Tri‐P, and 3DS. Importantly, poor correlations seemed to be driven by differences in acquisition rate. Currently, 2DS offers the most robust measurement of subclinical myocardial dysfunction. (Echocardiography 2012;29:334‐339)

Relation of heart-rate recovery to new onset heart failure and atrial fibrillation in patients with diabetes mellitus and preserved ejection fraction.

Diabetic autonomic neuropathy is a possible link between abnormal metabolism in type 2 diabetes mellitus (T2DM) and risk for atrial fibrillation (AF) and heart failure (HF). The aim of this study was to elucidate the association between attenuated heart rate recovery (HRR) and these manifestations of myocardial dysfunction in T2DM. Nine hundred fourteen consecutive patients with T2DM (mean age 56 ± 11 years, 508 men) without diabetes mellitus complications, with negative results on stress echocardiography, were enrolled. Patients with known cardiac disease were excluded. Demographics, clinical assessment, co-morbidities, and insulin use were collected prospectively. The association of HRR with new-onset HF and AF was sought using a Cox proportional-hazards model. There were 47 events (22 HF and 25 AF) during a median follow-up period of 7.8 years. Events were associated with age, exercise capacity, HRR, and left atrial volume index but not with baseline glycosylated hemoglobin, left ventricular mass index, or standard markers of diastolic function. In sequential Cox models for the combined outcomes, the model based on clinical data (age and gender; overall chi-square = 5.5) was not significantly improved by left atrial volume index (chi-square = 8.6, p = 0.10) or maximum METs (chi-square = 8.7, p = 0.07) but was significantly improved by adding HRR (chi-square = 19.7, p = 0.004). In addition, HRR provided significant incremental prognostic value regarding the composite end point (net reclassification improvement 19.2%, p = 0.04; integrated discrimination improvement 1.58%, p = 0.004). In conclusion, the association of HRR with subsequent HF and AF, independent of and incremental to left atrial volume index and other markers of abnormal cardiac structure and function, indicates a role for autonomic neuropathy as the link between metabolic and cardiac risk in patients with T2DM.

Grading diastolic function by echocardiography: hemodynamic validation of existing guidelines

BackgroundWhile echocardiographic grading of left ventricular (LV) diastolic dysfunction (DD) is used every day, the relationship between echocardiographic DD grade and hemodynamic abnormalities is uncertain.MethodsWe identified 460 consecutive patients who underwent transthoracic echocardiography within 24 h of elective left heart catheterization and had: normal sinus rhythm, no confounding structural heart disease, no change in medications between catheterization and echo, and complete echocardiographic data. Patients were grouped based on echocardiographic DD grade. Hemodynamic tracings were used to determine time constant of isovolumic pressure decay (Tau), LV end-diastolic pressure (LVEDP) and end-diastolic volume index at a pressure of 20 mmHg (EDVi20).ResultsNormal diastolic function was found in 55 (12.0 %) patients, while 132 (28.7 %) patients had grade 1, 156 (33.9 %) grade 2 and 117 (25.4 %) grade 3 DD. The median value for Tau was 46.9 ms for the overall population (interquartile range 38.6-58.1 ms), with a prevalence of a prolonged Tau (>48 ms) of 47.5 %. While there was an association between DD grade and Tau (p = 0.003), LV dysfunction (ejection fraction <50 %) was more strongly associated with increased Tau (p < 0.001) than was DD grade (p = 0.19). There was also an association between DD grade and LVEDP (p < 0.001), with both LV dysfunction (p = 0.029) and DD grade (p < 0.001) independently associated with LVEDP. Calculated EDVi20 was related to DD grade, but this relationship was driven by findings of paradoxically increased compliance in patients with severe DD.ConclusionsAlthough echocardiographic grading of DD was related to invasive hemodynamics in this population, the relationship was modest.

Reliability of updated left ventricular diastolic function recommendations in predicting elevated left ventricular filling pressure and prognosis

Background An updated 2016 echocardiographic algorithm for diagnosing left ventricular (LV) diastolic dysfunction (DD) was recently proposed. We aimed to assess the reliability of the 2016 echocardiographic LVDD grading algorithm in predicting elevated LV filling pressure and clinical outcomes compared to the 2009 version. Methods We retrospectively identified 460 consecutive patients without atrial fibrillation or significant mitral valve disease who underwent transthoracic echocardiography within 24 hours of elective heart catheterization. LV end‐diastolic pressure (LVEDP) and the time constant of isovolumic pressure decay (Tau) were determined. The association between DD grading by 2009 LVDD Recommendations and 2016 Recommendations with hemodynamic parameters and all‐cause mortality were compared. Results The 2009 LVDD Recommendations classified 55 patients (12%) as having normal, 132 (29%) as grade 1, 156 (34%) as grade 2, and 117 (25%) as grade 3 DD. Based on 2016 Recommendations, 177 patients (38%) were normal, 50 (11%) were indeterminate, 124 (27%) patients were grade 1, 75 (16%) were grade 2, 26 (6%) were grade 3 DD, and 8 (2%) were cannot determine. The 2016 Recommendations had superior discriminatory accuracy in predicting LVEDP (P < .001) but were not superior in predicting Tau. During median follow‐up of 416 days (interquartile range: 5 to 2004 days), 54 patients (12%) died. Significant DD by 2016 Recommendations was associated with higher risk of mortality (P = .039, subdistribution HR1.85 [95% CI, 1.03‐3.33]) in multivariable competing risk regression. Conclusions The grading algorithm proposed by the 2016 LV diastolic dysfunction Recommendations detects elevated LVEDP and poor prognosis better than the 2009 Recommendations.

Pericardiectomy is Associated with Improvement in Longitudinal Displacement of Left Ventricular Free Wall Due to Increased Counterclockwise Septal-to-Lateral Rotational Displacement.

BACKGROUND Pericardiectomy is an effective intervention for constrictive pericarditis. Speckle-tracking echocardiography can provide quantitative information not only about longitudinal strain (LS) but about longitudinal displacement (LD) and septal-to-lateral rotational displacement (SLRD). The aim of this study was to investigate whether pericardiectomy improves myocardial mechanics using speckle-tracking analysis. METHODS Eighty-three patients with constrictive pericarditis who underwent echocardiography were retrospectively assessed (mean age, 58 ± 12 years; 72 men; 50 idiopathic, 20 postoperative, four viral, three radiation, and six others) and compared with 20 healthy volunteers. LD and SLRD were measured from the apical four-chamber view and global LS from three apical views. RESULTS LD was less in the constrictive pericarditis group compared with control subjects (P < .001). Only lateral LS was significantly less than that of control subjects (P < .001), but septal LS was similar (P = .48). In pre- and post-pericardial surgery comparisons (n = 27), values of septal and lateral LD were almost identical (mean, 13.6 ± 4.7 vs 13.3 ± 5.4 mm; P = .70) before pericardiectomy, but septal LD decreased (mean, 9.3 ± 3.5 mm; P < .001) and lateral LD increased (mean, 16.8 ± 4.7 mm; P = .0106) after the surgery, even though the difference in LS between the septal and lateral walls decreased (from 5.6 ± 5.3% to 2.5 ± 4.2%, P = .008). Systolic whole-heart swinging motion significantly increased to a counterclockwise direction after surgery (mean SLRD, -0.8 ± 3.3° vs 2.1 ± 3.0°; P = .001). Although the change in SLRD after pericardiectomy was not different between patients with decreases and increases in New York Heart Association class, SLRD change was significantly greater in patients who received fewer diuretics after surgery (mean, 4.00 ± 0.91 vs 0.27 ± 1.47; P = .027). CONCLUSIONS After surgical removal of the pericardium, LD of the septal and lateral walls became significantly different, and counterclockwise SLRD increased, reflecting loss of pericardial support.

Association of the Active and Passive Components of Left Atrial Deformation with Left Ventricular Function

Background: Left atrial (LA) strain imaging enables the quantitative assessment of LA function. The clinical relevance of these measurements is dependent on the provision of information incremental to the left ventricular (LV) evaluation. The aim of this study was to test the hypothesis that LA pump function but not reservoir function is independent of measurement of LV mechanics. Methods: Echocardiography was undertaken in a community‐based study of 576 participants ≥65 years of age with one or more risk factors (e.g., hypertension, diabetes mellitus, obesity). Strain analysis was conducted using a dedicated software package, using R‐R gating. LV function was classified as normal in the presence of global longitudinal strain (GLS) (≤−18%) or global circumferential strain (GCS) (≤−22%). The associations between GLS or GCS and LA reservoir, conduit, and pump strain were assessed using univariate and multivariate linear regression. Results: Patients (mean age 71 ± 5 years, 54% women) with reduced GLS had higher blood pressure and rates of diabetes and obesity (P < .05). LA reservoir strain and conduit strain were lower in the group with impaired GLS (38.2 ± 7.3% vs 39.9 ± 6.4% [P = .004] and 18.7 ± 5.7% vs 20.5 ± 5.1% [P < .001], respectively), but there was no difference in LA pump strain (19.5 ± 5.5% vs 19.3 ± 4.6%, P = .72). GLS was independently associated with LA reservoir and conduit strain (P < .05) but not independently associated with LA pump strain (P = .91). Reduced GCS was associated with a larger body mass index, male sex, and diabetes (P < .05). There were no differences in LA reservoir, conduit, and pump strain in patients with normal and abnormal GCS (P > .05). Conclusions: The application of LA strain is specific to the component measured. LA pump strain is independent of LV mechanics. HighlightsLeft atrial strain analysis provides quantitative assessment of left atrial function.There is currently a lack of guidelines on image acquisition, electrocardiographic gating, and analysis methods.It is unclear if left atrial strain provides incremental information to left ventricular strain.This study compares the relationship between the three components of left atrial strain with left ventricular function to assess if left atrial function is primarily determined by left ventricular function.