Carly Jenkins

Left ventricular volume measurement with echocardiography: a comparison of left ventricular opacification, three-dimensional echocardiography, or both with magnetic resonance imaging

AIMS Both contrast enhanced (CE) two-dimensional echocardiography (2DE) and three-dimensional echocardiography (3DE) have been proposed as techniques to improve the accuracy of left ventricular (LV) volume measurements. We sought to examine the accuracy of non-contrast (NC) and CE-2DE and 3DE for calculation of LV volumes and ejection fraction (EF), relative to cardiac magnetic resonance imaging (MRI). METHODS AND RESULTS We studied 50 patients (46 men, age 63 +/- 10 year) with past myocardial infarction who underwent echocardiographic assessment of LV volume and function. All patients sequentially underwent NC-2DE followed by NC-3DE. CE-2DE and CE-3DE were acquired during contrast infusion. Resting echocardiographic image quality was evaluated on the basis of NC-2DE. The mean LV end-diastolic volume (LVEDV) of the group by MRI was 207 +/- 79 mL and was underestimated by 2DE (125 +/- 54 mL, P = 0.005), and less by CE-2DE (172 +/- 58 mL, P = 0.02) or 3DE (177 +/- 64 mL, P = 0.08), but EDV was comparable by CE-3DE (196 +/- 69 mL, P = 0.16). Limits of agreement with MRI were similar for NC-3DE and CE-2DE, with the best results for CE-3D. Results were similar for calculation of LVESV. Patients were categorized into groups of EF (< or =35, 35-50, >50%) by MRI. NC-2DE demonstrated a 68% agreement (kappa 0.45, P = 0.001), CE-2DE a 62% agreement (kappa 0.20, P = 136), NC-3DE a 74% agreement (kappa 0.39, P = 0.005) and CE-3DE an 80% agreement (kappa 0.56, P < 0.001). CONCLUSION CE-2DE is analogous to NC-3DE in accurate categorization of LV function. However, CE-3DE is feasible and superior to other NC- and CE-techniques in patients with previous infarction.

Use of myocardial deformation imaging to detect preclinical myocardial dysfunction before conventional measures in patients undergoing breast cancer treatment with trastuzumab

BACKGROUND Trastuzumab prolongs survival in patients with human epidermal growth factor receptor type 2-positive breast cancer. Sequential left ventricular (LV) ejection fraction (EF) assessment has been mandated to detect myocardial dysfunction because of the risk of heart failure with this treatment. Myocardial deformation imaging is a sensitive means of detecting LV dysfunction, but this technique has not been evaluated in patients treated with trastuzumab. The aim of this study was to investigate whether changes in tissue deformation, assessed by myocardial strain and strain rate (SR), are able to identify LV dysfunction earlier than conventional echocardiographic measures in patients treated with trastuzumab. METHODS Sequential echocardiograms (n = 152) were performed in 35 female patients (51 +/- 8 years) undergoing trastuzumab therapy for human epidermal growth factor receptor type 2-positive breast cancer. Left ventricular EF was measured by 2- and 3-dimensional (2D and 3D) echocardiography, and myocardial deformation was assessed using tissue Doppler imaging and 2D-based (speckle-tracking) strain and SR. Change over time was compared every 3 months between baseline and 12 months. RESULTS There was no overall change in 3D-EF, 2D-EF, myocardial E-velocity, or strain. However, there were significant reductions seen in tissue Doppler imaging SR (P < .05), 2D-SR (P < .001), and 2D radial SR (P < .001). A drop > or =1 SD in 2D longitudinal SR was seen in 18 (51%) patients; 13 (37%) had a similar drop in radial SR. Of the 18 patients with reduced longitudinal SR, 3 had a concurrent reduction in EF > or =10%, and another 2 showed a reduction over 20 months follow-up. CONCLUSIONS Myocardial deformation identifies preclinical myocardial dysfunction earlier than conventional measures in women undergoing treatment with trastuzumab for breast cancer.

Incremental Value of Strain Rate Analysis as an Adjunct to Wall-Motion Scoring for Assessment of Myocardial Viability by Dobutamine Echocardiography A Follow-Up Study After Revascularization

Background— Assessment of myocardial viability based on wall-motion scoring (WMS) during dobutamine echocardiography (DbE) is difficult and subjective. Strain-rate imaging (SRI) is quantitative, but its incremental value over WMS for prediction of functional recovery after revascularization is unclear. Methods and Results— DbE and SRI were performed in 55 stable patients (mean age, 64±10 years; mean ejection fraction, 36±8%) with previous myocardial infarction. Viability was predicted by WMS if function augmented during low-dose DbE. SR, end-systolic strain (ESS), postsystolic strain (PSS), and timing parameters were analyzed at rest and with low-dose DbE in abnormal segments. Regional and global functional recovery was defined by side-by-side comparison of echocardiographic images before and 9 months after revascularization. Of 369 segments with abnormal resting function, 146 showed regional recovery. Compared with segments showing functional recovery, those that failed to recover had lower low-dose DbE SR, SR increment (ΔSR), ESS, and ESS increment (ΔESS) (each P<0.005). After optimal cutoffs for the strain parameters were defined, the sensitivity of low-dose DbE SR (78%, P=0.3), ΔSR (80%, P=0.1), ESS (75%, P=0.6), and ΔESS (74%, P=0.8) was better though not significantly different from WMS (73%). The specificity of WMS (77%) was similar to the SRI parameters. Combination of WMS and SRI parameters augmented the sensitivity for prediction of functional recovery above WMS alone (82% versus 73%, P=0.015; area under the curve=0.88 versus 0.73, P<0.001), although specificities were comparable (80% versus 77%, P=0.2). Conclusions— The measurement of low-dose DbE SR and ΔSR is feasible, and their combination with WMS assessment improves the sensitivity of viability assessment with DbE.

Use of myocardial strain to assess global left ventricular function: A comparison with cardiac magnetic resonance and 3-dimensional echocardiography

BACKGROUND Ejection fraction (EF) plays a prominent role in clinical decision making but remains dependent on image quality and left ventricular geometry. Using magnetic resonance imaging (MRI-EF) as the reference standard, we sought whether global longitudinal strain (GLS) could be an alternative to the measurement of EF. METHODS Manual and semi-automated tracing was used to measure Simpsons biplane ejection-fraction (2D-EF) and 3D ejection fraction (3D-EF) and MRI in 62 patients with previous infarction. Global longitudinal strain was measured by 2-dimensional strain (2DS) in the apical views. Automated EF was calculated using speckle tracking to detect the end-diastolic and end-systolic endocardial border. RESULTS Strain curves were derived in all segments, with artifactual curves being excluded. The correlation of GLS with MRI-EF (r = -0.69, P < .0001) was comparable to that between 3D-EF and MRI (r = 0.80, P < .0001), and better than that between 2D-EF (r = 0.58, P < .0001) or automated EF and MRI (r = 0.62, P < .0001). To convert GLS into an equivalent MRI-EF, linear regression was used to develop the formula EF = -4.35 (strain + 3.9). Of the 32 patients with a normal MRI-EF (> or =50%), 75% had normal systolic function by GLS, whereas 85% of patients were recognized as having a normal 3D-EF. Fewer patients were recognized as normal by 2D-EF (70%, P = .14) and automated-EF (61%, P = .04). In those with >6 abnormal segments, the correlation of GLS with MRI-EF improved significantly (r = -0.77, P < .0001) and was similar to 3D-EF (r = 0.76, P < .0001). CONCLUSION Global longitudinal strain is an effective method for quantifying global left ventricular function, particularly in patients with extensive wall motion abnormalities.

Real-time 3D echocardiographic quantification of left atrial volume: multicenter study for validation with CMR

OBJECTIVES We studied in a multicenter setting the accuracy and reproducibility of 3-dimensional echocardiography (3DE)-derived measurements of left atrial volume (LAV) using new, dedicated volumetric software, side by side with 2-dimensional echocardiography (2DE), using cardiac magnetic resonance (CMR) imaging as a reference. BACKGROUND Increased LAV is associated with adverse cardiovascular outcomes. Although LAV measurements are routinely performed using 2DE, this methodology is limited because it is view dependent and relies on geometric assumptions regarding left atrial shape. Real-time 3DE is free of these limitations and accordingly is an attractive alternative for the evaluation of LAV. However, few studies have validated 3DE-derived LAV measurements against an accepted independent reference standard, such as CMR imaging. METHODS We studied 92 patients with a wide range of LAV who underwent CMR (1.5-T) and echocardiographic imaging on the same day. Images were analyzed to obtain maximal and minimal LAV: CMR images using standard commercial tools, 2DE images using a biplane area-length technique, and 3DE images using Tomtec LA Function software. Intertechnique comparisons included linear regression and Bland-Altman analyses. Reproducibility of all 3 techniques was assessed by calculating the percentage of absolute differences in blinded repeated measurements. Kappa statistics were used to compare 2DE and 3DE classification of normal/enlarged against the CMR reference. RESULTS 3DE-derived LAV values showed higher correlation with CMR than 2DE measurements (r = 0.93 vs. r = 0.74 for maximal LAV; r = 0.88 vs. r = 0.82 for minimal LAV). Although 2DE underestimated maximal LAV by 31 ± 25 ml and minimal LAV by 16 ± 32 ml, 3DE resulted in a minimal bias of -1 ± 14 ml for maximal LAV and 0 ± 21 ml for minimal LAV. Interobserver and intraobserver variability of 2DE and 3DE measurements of maximal LAV were similar (7% to 12%) and approximately 2 times higher than CMR (4% to 5%). 3DE classified enlarged atria more accurately than 2DE (kappa: 0.88 vs. 0.71). CONCLUSIONS Compared with CMR reference, 3DE-derived LAV measurements are more accurate than 2DE-based analysis, resulting in fewer patients with undetected atrial enlargement.

Incremental benefit of myocardial contrast to combined dipyridamole–exercise stress echocardiography for the assessment of coronary artery disease

Background—Although assessment of myocardial perfusion by myocardial contrast echocardiography (MCE) is feasible, its incremental benefit to stress echocardiography is not well defined. We examined whether the addition of MCE to combined dipyridamole-exercise echocardiography (DExE) provides incremental benefit for evaluation of coronary artery disease (CAD). Methods and Results—MCE was combined with DExE in 85 patients, 70 of whom were undergoing quantitative coronary angiography and 15 patients with a low probability of CAD. MCE was acquired by low-mechanical-index imaging in 3 apical views after acquisition of standard resting and poststress images. Wall motion, left ventricular opacification, and MCE components of the study were interpreted sequentially, blinded to other data. Significant (>50%) stenoses were present in 43 patients and involved 69 coronary territories. The addition of qualitative MCE improved sensitivity for the detection of CAD (91% versus 74%, P=0.02) and accurate recognition of disease extent (87% versus 65% of territories, P=0.003), with a nonsignificant reduction in specificity. Conclusions—The addition of low-mechanical-index MCE to standard imaging during DExE improves detection of CAD and enables a more accurate determination of disease extent.

Association of imaging markers of myocardial fibrosis with metabolic and functional disturbances in early diabetic cardiomyopathy

Background— Metabolic and vascular disturbances contribute to diabetic cardiomyopathy, but the role of interstitial fibrosis in early disease is unproven. We sought to assess the relationship between imaging markers of diffuse fibrosis and myocardial dysfunction and to link this to possible causes of early diabetic cardiomyopathy. Methods and Results— Hemodynamic and metabolic data were measured in 67 subjects with type 2 diabetes mellitus (age 60±10 years) with no cardiac symptoms. Myocardial function was evaluated with standard echocardiography and myocardial deformation; ischemia was excluded by exercise echocardiography. Calibrated integrated backscatter was calculated from parasternal long-axis views. T1 mapping was performed after contrast with a modified Look-Locker technique using saturation recovery images. Amino-terminal propeptides of procollagens type I and III, as well as the carboxy-terminal propeptide of procollagen type I, were assayed to determine collagen turnover. Subjects with abnormal early diastolic tissue velocity (Em) had shorter postcontrast T1 values (P=0.042) and higher calibrated integrated backscatter (P=0.007). They were heavier (P=0.003) and had worse exercise capacity (P<0.001), lower insulin sensitivity (P=0.003), and blunted systolic tissue velocity (P=0.05). Postcontrast T1 was associated with diastolic dysfunction (Em r=0.28, P=0.020; E/Em r=−0.24, P=0.049), impaired exercise capacity (r=0.30, P=0.016), central adiposity (r=−0.26, P=0.046), blood pressure (systolic r=−0.30, P=0.012; diastolic r=−0.49, P<0.001), and insulin sensitivity (r=0.30, P=0.037). The association of T1 with E/Em (&bgr;=−0.31, P=0.017) was independent of blood pressure and metabolic disturbance. Amino-terminal propeptide of procollagens type III was linked to diastolic dysfunction (Em r=−0.32, P=0.008) and calibrated integrated backscatter (r=0.30, P=0.015) but not T1 values. Conclusions— The association between myocardial diastolic dysfunction, postcontrast T1 values, and metabolic disturbance supports that diffuse myocardial fibrosis is an underlying contributor to early diabetic cardiomyopathy.

Association of cardiac autonomic neuropathy with subclinical myocardial dysfunction in Type 2 diabetes

OBJECTIVES The purpose of this study was to investigate the independent association between global cardiac autonomic neuropathy (CAN) and left ventricular (LV) dysfunction in addition to regional associations of LV dysinnervation and function, in patients with type 2 diabetes mellitus (T2DM). BACKGROUND CAN represents a potential mechanism in the etiology of nonischemic diabetic cardiomyopathy. METHODS Clinical measures of CAN based on total spectral power of heart rate variability and cardiac reflex testing and echocardiographic assessment of LV function were performed in 118 patients with type 2 diabetes mellitus. Systolic and diastolic function were defined at rest and peak exercise using peak systolic and peak early diastolic (Em) tissue velocities, calculated in 6 basal- and mid-segments using color tissue Doppler. Iodine 123-metaiodobenzylguanidine imaging was performed in 33 patients to directly quantify global (heart/mediastinum ratio) and regional LV sympathetic integrity. RESULTS Patients with CAN demonstrated higher resting heart rate, systolic and mean blood pressures, aortic stiffness, hemoglobin A(1c), and urine albumin/creatinine ratio, in addition to lower peak heart rate, chronotropic index, and exercise capacity. Diastolic function (Em) was associated with CAN, evidenced by total spectral power (r = 0.42, p < 0.001) and heart/mediastinum ratio (r = 0.41, p = 0.017). Diastolic function (Em) at rest and systolic function (peak systolic tissue velocity) at rest and exercise were significantly reduced in patients with CAN. Furthermore, total spectral power was associated with Em independent of age, hypertension, metabolic factors, and other relevant contributors to LV dysfunction (β = 0.20, p = 0.035). Relative regional tracer deficits indicative of local denervation were predominant in the anterior and lateral walls (p < 0.001). Associations with regional Em, independent of global iodine 123-metaiodobenzylguanidine uptake, were identified exclusively in mid-anterior (β = 0.45, p = 0.01) and mid-lateral walls (β = 0.34, p = 0.03). However, no association was found between regional denervation and systolic or diastolic dyssynchrony. CONCLUSIONS The diastolic dysfunction of type 2 diabetes mellitus shows associations with both regional markers of sympathetic integrity and clinical markers of autonomic neuropathy.

Augmentation index, left ventricular contractility, and wave reflection.

Augmentation index (AIx), a correlate of mortality, is thought to be influenced by left ventricular contractility and wave reflections. However, the relationship of AIx with left ventricular contractility changes has never been assessed, and the wave reflection theory has recently been questioned. This study sought to examine arterial waveform changes in response to reduced “wave reflection” and increased left ventricular contractility induced by dobutamine. Simultaneous radial tonometry (for AIx) and tissue Doppler echocardiography (for peak longitudinal systolic strain rate [SR] as an analogue of left ventricular contractility) were recorded at rest and peak dobutamine-induced stress in 50 patients (41 men; aged 62±10 years). From baseline to peak stress there was an increase in heart rate (70±11 to 127±17 bpm; P<0.001) and SR (−0.88±0.23 to −1.81±0.43 1/s; P<0.001), whereas AIx decreased (27±9% to −7±15%; P<0.001). There was also a greater increase in the systolic (compared with diastolic) pressure-time integral relative to cardiac cycle length (3.2±1.9 versus 1.8±1.1 mm Hg; P<0.001), indicating that wave reflection was not shifted into diastole as per the current belief. AIx was significantly associated with ejection duration (r=0.88), heart rate (r=−0.81), and SR (r=0.72; P<0.001 for all). However, when SR was heart rate corrected, there was no significant association with AIx (r=0.18; P=0.11). The strongest independent correlate of AIx was ejection duration, accounting for 78% variance (&bgr;=0.88; model R2=0.77; P<0.001). Neither SR (&bgr;=0.12; P=0.18) nor heart rate–corrected SR (&bgr;=0.02; P=0.72) was associated with AIx. We conclude that AIx is determined by chronotropic rather than inotropic effects, as well as factors other than wave reflection.

Measurement of left ventricular dyssynchrony in patients with ischaemic cardiomyopathy: a comparison of real-time three-dimensional and tissue Doppler echocardiography

Background: Real-time three-dimensional echocardiography (RT3DE) is an alternative modality to tissue Doppler imaging (TDI) for assessment of intraventricular dyssynchrony but its role is yet to be defined. Objectives: To (1) compare RT3DE and TDI for assessment of intraventricular dyssynchrony; (2) determine whether the two techniques agreed regarding the magnitude of dyssynchrony and identification of the site of maximal mechanical delay; and (3) investigate the reason for disagreement. Patients: 100 patients with ischaemic cardiomyopathy. Setting: Tertiary referral cardiac unit. Main outcome measures: Dispersion in time interval from QRS onset to peak sustained systolic tissue velocity by TDI (SD-TTV) and to minimal systolic volume by RT3DE (SD-T3D) between 12 ventricular segments. Results: RT3DE image quality was adequate for measurement of SD-T3D in 77 (77%) patients. In the whole population, SD-TTV was 40 (20) ms and SD-T3D was 8.3% (3.4%). RT3DE identified a smaller proportion of patients as having significant dyssynchrony than TDI (49 (64%) patients vs 32 (42%) patients; p<0.01). The correlation between SD-TTV and SD-T3D was poor (r = 0.11, p = NS). There was concordance between TDI and RT3DE in identifying the site of maximal mechanical delay in 12 (16%) patients. Validating the two techniques with anatomical M-mode (AMM) as a parameter of radial timing revealed better agreement with RT3DE than with TDI (χ2 = 11.8, p = 0.001). Conclusion: In patients with ischaemic cardiomyopathy, TDI and RT3DE show poor agreement for evaluating the magnitude of intraventricular dyssynchrony and the site of maximal mechanical delay. This may partly relate to their respective assessment of longitudinal versus radial timing.